Management of craniopharyngioma.

PURPOSE: The management of craniopharyngioma does not have a consensus. Extensive surgery may be associated with major complications. The purpose of this study was to evaluate local tumor control and survival after limited surgery and postoperative radiotherapy. METHODS AND MATERIALS: Thirty patients with craniopharyngioma were treated at SUNY Upstate Medical University in Syracuse, NY from 1967 to 2000. The group consisted of 13 males and 17 females, and the median age was 35 years. The median follow-up was 71 months. Only two patients underwent complete tumor resection. Eighteen patients underwent subtotal resection, and 10 underwent decompressive surgery (ventriculoperitoneal shunt or cyst aspiration). Most (20/ 28) patients who had less than total resection received immediate postoperative radiotherapy. Four patients received conventional radiotherapy for recurrence. Gamma knife radiosurgery was used as part of the primary treatment in two patients and at the time of local tumor recurrence in three patients. RESULTS: The local control rate, including after salvage treatment, was 91% and 83% at 5 and 10 years, respectively. Salvage was radiotherapy, gamma knife or surgery. Ultimate local tumor control appeared better for patients who underwent subtotal resection (100% and 89% at 5 and 10 years, respectively) than for those who did not undergo resection (61% and 61% at 5 and 10 years, respectively). The overall survival was 93% and 83% at 5 and 10 years, respectively. Two patients underwent gross total resection, and one patient experienced recurrence 6 years after the surgery and was treated by gamma knife radiosurgery. Both patients are well without recurrence at 3 and 7 years after the initial surgery. Survival also appeared to be improved for the group who underwent subtotal resection (100% and 90% at 5 and 10 years, respectively) versus those who did not undergo surgery (73% and 73% at 5 and 10 years, respectively). The dose of radiotherapy > or = 50 Gy had no impact on local control or survival. Ten patients experienced surgery-related complications, and five had radiotherapy-related complications, including visual, cranial nerve, motor, and endocrine deficits. CONCLUSION: The extent of surgery appears to be an important prognostic factor for predicting outcome, although this may represent selection bias. Long-term disease control is excellent after subtotal resection and postoperative radiotherapy. Encouraging initial results have been seen with gamma knife radiosurgery, and the potential for gamma knife radiosurgery to replace more extensive surgical resection should be further explored.

Effects of tirofiban plus heparin versus heparin alone on troponin I levels in patients with acute coronary syndromes.

Elevated serum troponins following an acute coronary syndrome (ACS) predict a poor clinical outcome. Glycoprotein (GP) IIb/IIIa inhibitors reduce adverse clinical outcomes in patients with ACS, although their effect on serum troponin I (TnI) in this setting has not been described. We therefore studied the effects of the GP IIb/IIIa inhibitor tirofiban on serum TnI levels in a group of patients in the Platelet Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms trial. Serial blood samples were obtained in 53 patients receiving the combination therapy of tirofiban/heparin and in 52 receiving heparin alone, and were analyzed for baseline, peak, and mean concentrations of TnI. Baseline TnI levels were not different between the combination therapy and heparin-only groups (1.6 +/- 3.0 vs 3.1 +/- 6.7 ng/ml, p = 0.15). The peak TnI level was significantly lower in the combination therapy group than in the heparin group (5.2 +/- 8.3 vs 15.5 +/- 29.1 ng/ml, p = 0.017), and mean levels over the initial 24-hour period were also significantly lower in the combination therapy group (3.2 +/- 5.0 vs 8.5 +/- 14.8 ng/ml, p = 0.016). In univariate analysis, combination therapy was associated with lower TnI levels, whereas in a multivariate model, the lower peak and mean TnI levels as a consequence of tirofiban/heparin compared with heparin monotherapy remained significant (peak, p = 0.029; mean, p = 0.035). Among patients with negative TnI at baseline, treatment with the combination of tirofiban/heparin compared with heparin monotherapy still resulted in significantly lower peak (2.5 +/- 5.4 vs 14.6 +/- 32.8 ng/ml, p = 0.024) and mean (1.2 +/- 2.6 vs 6.9 +/- 15.8 ng/ml, p = 0.029) TnI levels. In patients with ACS, therapy with the combination of tirofiban and heparin (compared with heparin treatment alone) resulted in lower serum TnI levels, suggesting reduced myocardial injury.

'Full dose' reirradiation of human cervical spinal cord.

With the progress of modern multimodality cancer treatment, retreatment of late recurrences or second tumors became more commonly encountered in management of patients with cancer. Spinal cord retreatment with radiation is a common problem in this regard. Because radiation myelopathy may result in functional deficits, many oncologists are concerned about radiation-induced myelopathy when retreating tumors located within or immediately adjacent to the previous radiation portal. The treatment decision is complicated because it requires a pertinent assessment of prognostic factors with and without reirradiation, radiobiologic estimation of recovery of occult spinal cord damage from the previous treatment, as well as interactions because of multimodality treatment. Recent studies regarding reirradiation of spinal cord in animals using limb paralysis as an endpoint have shown substantial and almost complete recovery of spinal cord injury after a sufficient time after the initial radiotherapy. We report a case of "full" dose reirradiation of the entire cervical spinal cord in a patient who has not developed clinically detectable radiation-induced myelopathy on long-term follow-up of 17 years after the first radiotherapy and 5 years after the second radiotherapy.

A simple backup for a radiosurgery treatment planning system.

To calculate the dose distribution and the number of monitor unit (MU) per arc, all radiosurgery systems utilize some sort of computer. These computers are, of course, subject to equipment malfunction such as problems with the magnetic tape drive, keyboard, mouse, etc. Since most radiosurgery procedures are quite invasive and time consuming, it is important to have a reliable and reasonably accurate backup system for planning the treatment. This paper will show that a simple PC based system, along with a digitizer, may be used as a backup for a commercial, VAX based radiosurgery system. A complete radiosurgery planning procedure was carried out on a head phantom with a target imbedded inside. The treatment planning and verification using the PC based system is also compared with that using the VAX based system.

The effect of cobalt-60 irradiation on bone marrow cellularity and alveolar osteoclasts.

The purpose of this study was to investigate the mechanisms of bone resorption in the rat dentoalveolar complex occurring as a result of orthodontic appliance therapy. Utilizing whole body radioactive cobalt 60 (Co60) irradiation in combination with orthodontic tooth movement, the activation, recruitment, and life span of osteoclasts was studied. Thirty-four adult Fischer 344 rats were irradiated with 10 and 20 Gray of Co60. Twelve days after irradiation, each rat was fitted with an orthodontic appliance; the rats were sacrificed 7, 14, or 21 days after appliance placement. To serve as controls, another group of 12 rats was subjected to orthodontic treatment only. Histologic sections were prepared from decalcified maxillary alveolar process, and osteoclasts were counted. In the control group, osteoclasts were presence in the periodontal membrane for four weeks after appliance placement, and the largest number of osteoclasts was observed in the second week. The smaller total irradiation dose (10 Gray, administered in 5 daily fractions) induced a transient reduction in the bone marrow cell count of more than 90%, followed by a complete rebound. The peak osteoclst number also was increased 110%. In contrast, the higher total dose (20 Gray, administered in 10 daily fractions) resulted in a reduction of 60% in bone marrow cellularity and a decrease in the peak osteoclast number by 40%. Fluctuations in bone marrow cellularity generally corresponded to similar variations in the osteoclast number, but there was an apparent lack of correspondence between bone marrow cell and white blood cell values. The total period of osteoclastic presence in the periodontal membrane following orthodontic activation, normally four weeks in duration, was reduced by one week in the irradiated animals. These findings lead us to speculate that the mechanisms of osteoclast activation and recruitment following orthodontic appliance therapy may involve three consecutive waves of osteoclast maturation. The total duration of osteoclastic bone resorption lasts 4 weeks, but the osteoclast lie span is calculated to be 9 to 10 days (9 days x 3 waves = 27 days). If the results of this study are proved to be reproducible, a scientific basis may have been provided to support the common practice in orthodontics wherein the duration between orthodontic appointments is 4-5 weeks.

Glomus jugulare tumors. Long-term control by radiation therapy.

The records of 49 patients with glomus jugulare tumor seen at the University of Virginia from 1932 to 1985 were retrospectively reviewed with the objective of assessing long-term results of treatment. Follow-up ranged from 5 to 31 years, with a minimum of 10 years in 36 patients (73%). According to McCabe's classification, 17 patients (35%) were Group I, 11 patients (22%) were Group II, and 21 patients (43%) were Group III. Analysis by therapeutic technique revealed that 20 patients received surgery alone (41%), 15 patients received radiation therapy alone (31%), and 14 patients received combined therapy (28%). Only 7 patients (14%) have had clinical or radiologic evidence of disease progression. Three of these patients were treated by surgery alone and three by a combination of surgery and radiation, but the dose was less than 4000 cGy. Only one patient treated by radiation therapy alone or with surgery and radiation to a dose in excess of 4000 cGy demonstrated disease progression. Salvage radiation therapy was given to three of the seven patients when progressive disease was detected. Radiation therapy is an effective treatment for glomus jugulare tumor with minimal late progression of disease in adequately treated patients and no significant long-term complications.

Advantages of using high activity 125I seeds in temporary interstitial breast implants.

There has been considerable interest in the use of high activity 125I sources as a substitute for 192Ir seeds for removable implants of the breast and prostate. 125I seeds with an initial activity of approximately 5 mCi per seed, loaded in special afterloading nylon catheters, are used to improve dose distribution in the tumor volume and minimize dose to the adjacent critical organs and normal tissues. Seed spacing in strands is adjusted to maintain a dose rate of 40-60 cGy per hour at a distance of 5 mm from the plane of the implant. Implants custom loaded with 125I sources achieve superior isodose distribution compared to implants loaded with standard 192Ir seed strands. High activity 125I seeds also offer the advantage of reduced exposure to radiation oncology staff, nurses, and visitors leading to better patient care. Due to reduced exposure to personnel, the accuracy of the actual implant geometry can be verified by taking a localization film with actual 125I sources placed in the tumor bed.

A phase I-II trial of multimodality management of bulky gynecologic malignancy. Combined chemoradiosensitization and radiotherapy.

Between December 1983 and December 1987, there were 44 patients with bulky, nonresectable squamous cell carcinomas of the gynecologic tract (cervix, 36; vagina, eight) who were treated with concomitant chemotherapy and radiotherapy. Chemotherapy consisted of 5-fluorouracil (5-FU) 1g/m2 given by continuous intravenous infusion on days 1 through 4 and mitomycin C 10 mg/m2 given intravenously on day 1. External-beam irradiation was started on day 1 with a total calculated dose of 5000 cGy in 25 fractions employed. This was followed by brachytherapy. With a mean follow-up of 30.3 months and a median of 28 months, local control has been achieved in 32 of 44 patients (73%). The overall response rate was 88% (3-month partial response, 43%; 3-month complete response, 45%; 8-month partial response, 15%; 8-month complete response, 73%). Analysis of complications by Radiation Therapy Oncology Group (RTOG) criteria did not demonstrate an increase in acute or late complications.

Primary malignant extragonadal germ cell tumors. An analysis of the effect of the effect of radiotherapy.

A retrospective analysis was performed on all patients diagnosed with biopsy-proven extragonadal germ cell tumors at the University of Virginia (Charlottesville, VA), The Medical University of South Carolina (Charleston, SC), the Bethesda Naval Hospital (Bethesda, MD), and The Medical College of Virginia (Richmond, VA) for the time period of January 1965 to December 1984. A total of 54 patients were treated with the initial sites of presentation observed: mediastinum, 26; central nervous system, 14; retroperitoneum, eight; and sacrococcygeal region, six. Megavoltage irradiation was used in 44 patients with a dose range of 2400 to 5580 cGy (mean, 4213 cGy). With a minimum follow-up of 4.0 years and a mean follow-up of 10.8 years, the 5-year actuarial survival for the entire population was 57.8%. Local control was achieved in 26 of 44 (59%) of the irradiated population. Factors of prognostic significance included histologic type at presentation, site of presentation, and radiation doses greater than or equal to 4000 cGy. Radiotherapy appears to be an effective modality in patients with extragonadal seminomas; however, the nonseminomatous tumors do not appear to be as radioresponsive.

Early glottic carcinoma: patterns and predictors of relapse after definitive radiotherapy.

Although definitive radiotherapy in the management of early glottic carcinomas continues to offer excellent control, a small proportion of patients will have relapse. Between January 1972 and December 1984, 148 patients with squamous cell carcinoma of the glottis (stage I in 95 patients and stage II in 53 patients) had definitive radiotherapy at the University of Virginia Medical Center. We retrospectively analyzed patient data in an attempt to identify patients at risk for relapse and the patterns of failure. The three-year determinate survival for the entire population was 94.5% (stage I--100%, stage II--86%). Twenty of the 148 patients (14%) had relapse after radiotherapy. Failure in the primary site alone was observed in 17 patients (11%), two patients (1%) had relapse in the lymphatics of the neck without evidence of primary recurrence, and one patient (0.7%) had both neck and distant disease. Of the 19 patients who had definitive surgery after recurrence, 13 (68%) were successfully salvaged. Multivariate analysis was done to identify independent factors on relapse and survival. Statistically significant factors included persistent hoarseness after radiotherapy (P = .00005), impaired cord mobility (P = .00002), subglottic extension (P = .02), anterior commissure extension (P = .001), and multifocal involvement in stage I disease (P = .0008). We conclude that a majority of the small patient population with recurrent glottic carcinoma after radiotherapy may be salvaged with surgery, and we have identified patients at increased risk for recurrence.

Treatment of small-cell carcinoma of the cervix with weekly combination chemotherapy.

Three patients with small-cell carcinoma of the cervix entered a pilot study of combination chemotherapy with agents that are not cross-resistant. Two patients had local disease and the third had extensive metastatic disease of the liver. The regimen consisted of weekly chemotherapy for 16 weeks with cisplatin, vincristine, methotrexate, doxorubicin, cyclophosphamide and etoposide followed by radiotherapy and/or surgery. The two patients with local disease achieved a pathological complete response, with no evidence of disease at 24 months and 15 months from diagnosis. The third patient achieved a partial response and is alive at 13 months with progressive disease. Side-effects were tolerable.

A new, rapid safe method for local radiation of intrathoracic sites.

A technique for intraoperative, intrathoracic placement of afterloading catheters for post-thoracotomy radiation therapy is described. This technique offers speed and simplicity and requires no advance planning of radiation therapy. It uses materials that are readily available in operative theaters and radiation oncology units. No radiation exposure of operating room personnel is involved. It also avoids the mechanical problems of crimping and dislodgment associated with the traditional method of individual placement of small afterloading catheters for local radiation therapy. Isodose curves derived from radiographs showing postsurgical source positions demonstrated that it was possible to achieve a uniform therapeutic radiation dose distribution to the chest wall at the site of desired radiotherapy.

Cisplatin, 5-fluorouracil, mitomycin C, and concurrent radiation therapy with and without esophogectomy for esophageal carcinoma.

Twenty-nine patients with carcinoma of the esophagus were treated with 5-fluorouracil (5-FU) (1000 mg/m2/d as a continuous intravenous [IV]infusion on days 1 through 4), cisplatin (100 mg/m2 IV on day 1), mitomycin C (10 mg/m2 IV on day 1), and concurrent radiation therapy (4500 cGy/4.5 wk). If no disease progression was observed, operable patients underwent surgery 4 to 6 weeks after completion of radiation therapy. A thoracotomy with a gastric pull-through operation was performed in the first six patients. Subsequently, a transhiatal ("blunt") esophagectomy was used. Twenty-five patients had squamous cell histology and four had adenocarcinoma. Of 25 patients with squamous cell carcinoma, 13 underwent esophagectomy. The clinical complete response rate was 61% (eight of 13 patients), with a pathologic complete remission documented in five of 13 patients (38%). The overall local tumor sterilization rate was 53% (seven of 13 patients). In the 12 patients who did not undergo surgery after chemoradiotherapy, four had a complete clinical response (33%) and five had a partial response (41%). Symptoms or signs of local disease recurrence or stricture were noticed in ten of 12 patients who did not undergo surgery (83%), compared with 28% of patients who underwent surgery. The median survival time of the group receiving surgery was 10 months, compared with 5 months for those who did not undergo operation (P = 0.027). Patients undergoing transhiatal esophagectomy had shorter postoperative hospital stays and fewer serious complications, compared with patients undergoing transthoracic esophagectomy. The use of chemoradiotherapy and transhiatal esophagectomy for esophageal carcinoma should be evaluated using alternative sequences of treatment (e.g., postoperative therapy) to reduce toxicity while maintaining local control of disease.

Definitive radiotherapy in the management of stage I and II carcinomas of the glottis.

Definitive radiotherapy for early glottic carcinoma continues to offer excellent control and the advantage of voice preservation. In the 13 years from January 1972 through December 1984, there were 187 patients diagnosed with squamous cell carcinoma of the glottis at the University of Virginia Medical Center. One hundred forty-eight patients were treated with definitive radiotherapy as the initial management. The 3-year disease-free survival for the irradiated population was 93.6% in stage I and 75.5% in stage II. Twenty patients had recurrences following radiotherapy, and 13 of 20 were successfully surgically salvaged for an overall determinate survival of 100% in stage I and 85.7% in stage II at 3 years. These statistics are comparable to those from our previous 16-year review of 147 patients from 1956 through 1971. Factors of prognostic significance were persistent hoarseness after radiotherapy, impaired cord mobility, subglottic extension, and multiple sites of involvement in stage I. We conclude that definitive radiotherapy offers excellent survival and that a majority of the small number of treatment failures can be managed with surgical salvage.

Treatment of small cell carcinoma with weekly combination chemotherapy. A pilot study.

We conducted a prospective non-randomized pilot study to evaluate the response rate and toxicity of weekly combination chemotherapy in pulmonary and extrapulmonary small cell carcinoma. A consecutive collection of 13 patients seen at the University of Virginia Medical Center was entered into the study after written informed consent. Ten of these patients had small cell carcinoma of the lung (4 with limited disease and 6 with extensive disease) and 3 patients had extrapulmonary small cell carcinoma (esophagus, cervix, and larynx). The treatment regimen consisted of weekly chemotherapy for 16 weeks using six cytotoxic agents (cisplatin, vincristine, methotrexate, adriamycin, cyclophosphamide, and VP-16) in different combinations followed by radiotherapy to the primary site. To date, ten patients have completed chemotherapy and radiotherapy with 9 (90%) achieving a complete response. The overall objective response rate was 100%. Of the remaining 3 patients who are currently receiving treatment, one achieved a complete response and two are showing significant responses. This ongoing trial shows that a weekly combination chemotherapy regimen is effective in producing high response rates in small cell carcinoma.

Whole abdominal radiotherapy following cytoreductive surgery and chemotherapy in ovarian carcinoma.

Persistent or recurrent disease following surgery and chemotherapy in ovarian carcinoma remains a major therapeutic dilemma. Between January 1980 and December 1985, there were 26 patients who had previously undergone cytoreductive surgery and chemotherapy and were treated with external beam radiotherapy. Twenty-one of these patients had been treated with platinum-adriamycin-cytoxan (PAC) regimen and 5 were treated with other combinations. Surgical reevaluation was performed in 21 of the 26 patients and only 4/21 (19%) patients were free of disease. All 26 patients were irradiated with a planned dose of 2500 cGy/100 cGy/day or 2280 cGy/120 cGy/day to the whole abdomen and a final calculated dose to the pelvis of 4500 cGy. Initial evaluation showed a 3-year actuarial survival rate of 51% and a disease-free survival rate of 42%. Follow-up analysis yields survivals of 45 and 35%, respectively. Severe gastrointestinal complications were observed in 3/26 patients and all hematologic complications resolved. Variables of prognostic significance were chemotherapy tolerance, grade, and volume of residual disease. We conclude that a proportion of patients with disease following cytoreductive surgery and chemotherapy may be salvaged with abdominopelvic irradiation.

Results of the radiotherapeutic management of carcinoma of the cervix with emphasis on the influence of histologic classification.

The histology of 365 of 396 patients (92%) treated with radiation therapy at the University of Virginia from 1968 to 1978 has been reviewed. Staging and treatment policies were consistent throughout this period, and have enabled the influence of histologic classification on treatment results to be evaluated. Large cell nonkeratinizing carcinoma (LCNK) was the most common type, 69%; followed by keratinizing (KSCC), 13%; and adenocarcinoma, 6.6%. Other varieties included adenosquamous, 3.6%; small cell undifferentiated carcinoma, 2.7%; papillary squamous, 1.6%; and glassy cell, 1.4%. Overall survivals by stage were similar to those reported from other centers. When examined by histologic type, the 5-year survival rates ranged from 64% for adenosquamous to 13% for small cell. The most common varieties, LCNK and KSCC, had survival rates of 61% and 40% (P = 0.008). Considering both stage and histologic type, the differences between LCNK and KSCC persisted and were significant for Stage IIB (P = 0.023). Of particular interest are the poor results in small cell carcinoma and adenocarcinoma, except in the earliest stages, and the good results for adenosquamous carcinoma. The patterns of failure by histologic type showed that local failures were higher in cases of KSCC than in LCNK, indicating a probable difference in radiosensitivity. Distant spread was similar for both types. Both small cell carcinoma and adenocarcinoma showed high rates of distant spread and local failure except in the early stages. Considering survival and failure rates, three prognostic groups could be identified. In descending order of curability these were: 1) LCNK and adenosquamous carcinoma; 2) KSCC, papillary squamous carcinoma, and adenocarcinoma; and 3) small cell carcinoma and glassy cell carcinoma.

Primary central nervous system germ cell tumors. Effect of histologic confirmation on radiotherapy.

Primary malignant intracranial germ cell tumors are rare lesions responsible for only 0.5% of all central nervous system (CNS) malignancy. With stereotactic localization these lesions can be safely biopsied, and histologic confirmation will affect the ultimate prognosis. This report is a multi-institutional retrospective analysis of 33 patients diagnosed with a primary CNS germ cell tumor. Tumors in 14 patients (42%) were histologically confirmed (13 germinoma and one embryonal cell carcinoma); 19 patients were treated with a presumptive diagnosis. All patients were irradiated with a dose range of 3950 cGy to 6000 cGy to the primary lesions. Eight patients received craniospinal irradiation, and 25 patients were locally treated. The 5-year actuarial survival for the entire population was 64%. The survival rate in patients with histologic confirmation was 79% versus 53% in the unbiopsied population. Radiation doses greater than 5000 cGy, radiotherapy volume, and age were prognostic factors in determining survival.