Usefulness of tumor volumetry by magnetic resonance imaging in assessing response to radiation therapy in carcinoma of the uterine cervix.

PURPOSE: Clinical evaluation of tumor size in cervical cancer is often difficult, and clinical signs of radiation therapy failure may not be present until well after completion of treatment. The purpose of this study is to investigate early indicators of treatment response using magnetic resonance (MR) imaging for quantitative assessment of tumor volume and tumor regression rate before, during, and after radiation therapy. METHODS AND MATERIALS: Thirty-four patients with cervical cancer Stages IB [5], IIB [8], IIIA [1], IIIB [14], IVA [3], IVB [1], and recurrent [2] were studied prospectively with four serial MR examinations obtained at the start of radiation therapy, at 2-2.5 weeks (20-24 Gy), at 4-5 weeks (40-50 Gy), and 1-2 months after treatment completion. Tumor volume was assessed by three-dimensional volumetric measurements using T2-weighted images of each MR examination. The volume regression rate was generated based on the four sequential MR studies. These findings were correlated with local control, metastasis rate, and disease-free survival. Median follow-up was 18 months (range: 9-43 months). RESULTS: The tumor regression rate after a dose of 40-50 Gy correlated significantly with treatment outcome. The actuarial 2-year disease-free survival was 88.4% in patients with tumors regressing to < 20% of the initial volume compared with 45.4% in those with > or = 20% residual (p = 0.007). The incidence of local recurrence was 9.5% (2 out of 21) and 76.9% (10 out of 13), respectively (p < 0.001). Analysis by initial tumor volume showed that this observation was valid in patients with initial volumes between 40 and 100 cm3. Analysis by FIGO stage confirmed this observation in all patients except those with Stage IB. CONCLUSION: Sequential tumor volumetry using MR imaging appears to be a sensitive measure of the responsiveness of cervical cancer to irradiation. Treatment response can be assessed as early as during the course of radiation therapy by measurement of initial tumor volume and regression rate at 40-50 Gy. In patients with large (> 40 cm3) and advanced (Stage > or = IIIA) tumors, this technique may be helpful in supplementing the clinical examination for response assessment. The identification of patients at high risk for treatment failure may ultimately lead to improved clinical outcome.

Cost-effectiveness of high-dose MR contrast studies in the evaluation of brain metastases.

PURPOSE: To investigate the cost-effectiveness of high-dose MR contrast studies in the management of brain metastases. METHODS: During the phase III clinical trial of high-dose contrast studies (0.3 mmol/kg), 11 of 27 patients were judged by the reviewers to have potential treatment changes based on the additional information provided by the high-dose studies. We retrospectively evaluated how many of these 27 patients had actual treatment changes because of the results of the high-dose study. Using the fee schedule at our institution, the cost-effectiveness was analyzed based on the cost savings from treatment changes and the additional expense of implementing the high-dose studies. RESULTS: A total of 3 craniotomies ($22,800 each) and 2 aggressive courses of radiation therapy ($1122 each) were avoided in 4 patients because of the additional lesions detected by the high-dose studies. This resulted in a treatment cost savings of $70,644. The extra expense for implementing the high-dose study is $9126 for a single injection in all 27 patients, $9295 for 2 separate injections completed in 1 visit in the 11 patients, and $11,154 for 2 separate injections completed in 2 separate visits. The cost savings in management (diagnosis and treatment) therefore ranged from $59,490 to $61,518 for all patients and from $2203 to $2278 per patient. CONCLUSION: Based on our limited data, the high-dose study seems to impact positively on the cost-effectiveness in the management of brain metastases. However, because our study had limitations, our results need to be confirmed with a larger patient population and a more standardized treatment approach and fee schedule.

Morphology and pathology of radiation-induced esophagitis. Double-blind study of naproxen vs placebo for prevention of radiation injury.

Radiation-induced esophagitis can cause substantial morbidity. Experiments in lab animals have shown that pretreatment with indomethacin protects the esophagus from radiation damage. We conducted a prospective, double-blind, randomized trial of naproxen vs placebo in patients undergoing thoracic radiation therapy for lung cancer. Twenty-eight patients were enrolled, of which 26 completed the study. Sixteen patients were given a short course of radiation (30 Gy/10 fractions/2 weeks), and 10 patients were given a longer course and a larger dose (40-50 Gy/25 fractions/5 weeks). Half of the irradiated patients were treated with naproxen, 375 mg, taken orally twice a day, and half were given an identical placebo. All patients were given ranitidine 300 mg, taken orally once a day. Study drugs were taken throughout the course of radiation. Endoscopy with esophageal biopsies and brushings was performed before and on the last day of treatment. Patients kept a daily diary for symptom scoring. Symptoms such as chest pain, dysphagia, odynophagia, and/or heartburn were reported in 15 patients from both subgroups, resulting in diet restriction to liquids only in eight patients and requiring temporary discontinuation of radiation therapy in one of them. Approximately half the patients in each subgroup developed esophagitis, usually mild and usually limited to the proximal esophagus. Severity of symptoms was not proportional to the severity of esophagitis. Candidiasis was documented in eight patients, but only four had symptoms that were severe in one. We conclude that acute radiation injury to the esophagus is observed in approximately half the patients receiving radiation therapy and can result in substantial morbidity.(ABSTRACT TRUNCATED AT 250 WORDS)

Results of radical perineal prostatectomy with adjuvant brachytherapy.

Retrospective analysis of outcome in 137 patients who underwent radical perineal prostatectomy and bilateral injection of gold-198 implants into the periprostatic tissues and/or neurovascular pedicles as treatment for prostatic adenocarcinoma was performed. Patients had undergone treatment between 1975 and 1985. Local recurrence developed in 22 patients (16.1%) and distant metastases developed in 33 (24.1%). Clinical and surgical staging of disease and Gleason grading of pathologic specimens were performed retrospectively. Kaplan-Meier local recurrence, freedom from relapse (FFR), and survival rates decreased with increasing stage and pathologic grade. With clinical staging, these rates were not statistically different from previous rates achieved with external beam radiation therapy, and with pathologic staging, they were not statistically different from previous rates achieved with prostatectomy. The authors conclude that (a) 5-year follow-up is inadequate to determine local control rates after prostatectomy; (b) use of implants did not improve local control, FFR, or survival rates of 10 years; and (c) method of staging probably has more effect on local control, FFR, and survival rates than does treatment modality.

Extended field irradiation for carcinoma of the uterine cervix with positive periaortic nodes.

Forty-three patients were treated with extended field irradiation for periaortic metastasis from carcinoma of the uterine cervix (FIGO stages IB-IV). Twelve patients (28%) remained continuously free of disease to the time of analysis or death from intercurrent disease, 20 (46%) had persistent cancer within the pelvis, 11 (26%) had persistent periaortic disease, and 23 (53%) developed distant metastasis. The actuarial 5-year survival rate was 32%. The results correlated well with the periaortic tumor burden at the time of irradiation. None of 19 patients (0%) with microscopic or small (less than 2 cm) periaortic disease had periaortic failures, compared to 29% (4/14) of those with moderate-sized (2-5 cm) disease and 70% (7/10) of those with massive (greater than 5 cm) periaortic metastasis. Similarly, the 5-year survival rates were 50% (6/12) with microscopic disease, 33% (2/6) with small gross disease, 23% (3/13) with moderate-sized disease, and 0% (0/10) with massive periaortic metastases. Only 10% (1/10) of patients whose tumor extended to the L1-2 level survived 5 years, compared with 31% (9/29) of those whose disease extended no higher than the L3-4 level. The periaortic failure rates correlated to some extent with the dose delivered through extended fields, although the difference was not statistically significant. Only 8% (1/13) of those who had undergone extraperitoneal lymphadenectomies developed small bowel complications, compared with 25% (7/29) of those who had had transperitoneal lymphadenectomies. The incidence of small bowel obstruction was 8% (1/13) following periaortic doses of 4000-4500 cGy, 10% (1/10) after 5000 cGy, and 32% (6/19) after approximately 5500 cGy. From this, we concluded that the subset of patients who would benefit most from extended field irradiation are those in whom the residual disease in the periaortic area measures less than 2 cm in size at the time of treatment, whose disease extends no higher than L3, and whose cancer within the pelvis has a reasonable chance of control with standard radiation therapy techniques.

A comparison of the roles of surgery and radiation therapy in the management of carcinoma of the female urethra.

Between 1939 and 1986, 42 patients with carcinoma of the female urethra were treated with surgery and/or radiation therapy at the University of Iowa. Ten patients were treated with surgery alone, 28 with radiation therapy alone, and 4 with combined surgery and radiation therapy. Seventeen patients (40%) developed persistent or recurrent disease at the primary site and 15 (36%) had failures in the inguinal nodes. The actuarial 5-year survival rate was 33.5%. Only 36% (10/28) of patients treated with radiation therapy had local failures, compared to 60% (6/10) of those treated with surgery alone. The best results were achieved with combined interstitial and external beam irradiation. Whereas 57% (8/14) of patients who were treated with combined interstitial and external beam irradiation were alive NED at 3 years, none of 7 patients (0%) treated with interstitial implants only and 2 of 7 patients (29%) treated with external beam irradiation alone were alive NED at 3 years. There was a significantly lower inguinal failure rate in patients who received treatment to the inguinal nodes (10%) than in those who did not receive inguinal area treatment (52%), and this translated into a superior 5-year survival for those patients (60% vs 18%). Survival rates did not correlate with histopathologic type in this series, although there were differences in the patterns of failure. Survival rates did correlate well with clinical stage.

The role of radiation therapy in the management of ependymomas of the spinal cord.

Twenty patients with biopsy-proven ependymomas of the spinal cord were treated between 1960 and 1984-7 with surgery only, 3 with radiation therapy only, and 10 with surgery and postoperative radiation therapy. Of these, 2 patients developed recurrent tumor at the primary site, 3 developed a recurrent tumor in the thecal sac, and 1 developed distant metastasis. The absolute 5- and 10-year survival rates were 95% (19/20) and 86% (12/14), respectively. None of 13 patients who were treated with radiation therapy only or combined surgery and postoperative radiation therapy developed recurrent tumor at the primary site, and none of 7 patients who received thecal sac irradiation developed thecal sac recurrences. In contrast, 2 of 7 patients (29%) treated with surgery alone developed recurrent tumor at the primary site, and 3 of 13 patients (23%) who received no thecal sac irradiation developed a recurrent tumor in the thecal sac. The failure rates following surgery were greatest in patients who had tumor removed in a piecemeal fashion (43%, 6/14). The results show that radiation therapy is probably not necessary if the tumor has been removed completely in an en bloc fashion. However, radiation therapy is needed if the tumor has been incompletely removed or removed in a piecemeal fashion. If the tumor has been removed in a piecemeal fashion, the radiation portals should be extended to include the thecal sac. Histologic subtypes influenced the pattern of recurrence. Myxopapillary ependymomas and high grade cellular ependymomas appear to be more likely to recur in the thecal sac. However, no big difference could be detected in local recurrence.

Preliminary results of a pilot study of pentoxifylline in the treatment of late radiation soft tissue necrosis.

Between September 1988 and August 1989, 12 patients with 15 sites of late radiation necrosis of the soft tissues were treated with pentoxifylline, a hemorrheologic agent that has been used to treat a variety of vasculo-occlusive disorders. Four of these necroses were located in the oromucosa, four in the mucosa of the female genitalia, and seven in the skin. At the time of analysis, 87% (13/15) of the necroses had healed completely, and one was partially healed. Furthermore, the time-course of healing with pentoxifylline was significantly less than the duration of nonhealing prior to pentoxifylline (average: 9 weeks vs 30 1/2 weeks). All patients had pain relief. These results indicate that pentoxifylline can contribute to the healing of soft tissue radiation necrosis. They also support the concept that late radiation injury in skin and mucosa is at least partly due to vascular injury.

The role of radiation therapy in the treatment of solitary plasmacytomas.

Between 1960 and 1985, 30 patients with solitary plasmacytomas were treated with radiotherapy at the University of Iowa: 13 patients with extramedullary plasmacytomas (EMP) and 17 with solitary plasmacytomas of bone (SPB). The local control rates were 92% for patients with EMP and 88% for those with SPB. Two of nine patients (22%) with EMP treated to the primary tumor only developed regional lymph node metastasis, indicating the need for elective irradiation of this area. The most common pattern of failure in both groups was progression to multiple myeloma. This occurred in 23% of the patients with EMP and 53% of those with SPB. The time course of progression to multiple myeloma differed for the two groups. All of those who progressed to multiple myeloma in the EMP group did so within 2 years, whereas a significant number of those in the SPB group progressed more than 5 years after initial therapy. None of five patients who received adjuvant chemotherapy in the SPB group progressed to multiple myeloma, compared to 75% (9/12) of the patients who did not receive chemotherapy.

The role of kilovoltage irradiation in the treatment of keloids.

This is a retrospective analysis of the results of kilovoltage irradiation given to prevent the regrowth of 203 keloids excised at the University of Iowa Hospitals and Clinics, Iowa City, Iowa, Lutheran Hospital in Moline, Illinois, and Mercy Hospital in Cedar Rapids, Iowa. We found that a minimum follow-up of 1 year is needed to evaluate the results of post-excisional kilovoltage x-ray therapy. A dose versus response effect was also observed. Although it is desirable to use the lowest possible dose of radiation that is likely to be effective, the likelihood of failure is too great to justify the routine use of doses of less than 900 cGy regardless of how they are fractionated or when they are given. It appears that the total dose of irradiation that is given to prevent the regrowth of an excised keloid is more important than when irradiation is started, the size of the largest fraction given, whether the irradiation is completed in 1 week or 3, or where the keloid has grown. When a small number of keloids were irradiated less than 1 year after they first appeared greater than or equal to 1500 cGy were sufficient to control 90% of them without re-excision.

Analysis of movement of intrathoracic neoplasms using ultrafast computerized tomography.

Twenty patients with intrathoracic neoplasms were evaluated with ultrafast (cine) computerized tomography to determine the contribution of tumor motion to geographic errors. The treatment portals were setup with conventional simulation techniques and then scanned with cine computerized tomography. Eight tomographic levels were studied, 10 images per level over 7 seconds time. Major geographic misses were detected in three patients (15%), and minor geographic misses in an additional three (15%). The greatest tumor movement was noted in lesions located adjacent to the heart or aorta or near the diaphragm. Five of six hilar lesions showed significant lateral motion (average = 9.2 mm) with cardiac contraction, and three of four lower lobe lesions showed significant craniocaudal movement with respiration. Mediastinal lesions moved an average of 8.7 mm laterally. Lesions in the upper lobes showed minimal movement (average = 2.2 mm), and tumors attached to the chest wall showed no measurable movement.

A comparison of the roles of surgery and radiation therapy in the management of craniopharyngiomas.

Fifty-two patients with craniopharyngioma were seen between January 1961 and July 1986. Of these, 40 were treated with surgery alone, 8 with surgery and postoperative radiotherapy, and 3 with radiotherapy alone. One patient received no treatment. For the group treated with surgery alone, 33% (13/40) had local tumor control, 42.5% (17/40) developed major complications, and 71% (25/35) survived 5 years. With surgery and postoperative radiotherapy, 100% (8/8) had local tumor control, 25% (2/8) developed major complications, and 100% (7/7) survived 5 years. Two of the three patients treated with radiotherapy alone had local tumor control and the third was salvaged with surgery. The "complete resection" rate for 32 patients treated with radical surgery was 63% (20/32). Tumor control was achieved in 50% (10/20) of the patients treated with "complete resection" without radiotherapy, in 15% (3/20) of the patients treated with "incomplete resection" without radiotherapy, and in 100% (8/8) of the patients treated with "incomplete resection" and postoperative radiotherapy. In this series, doses of 5000-5500 cGy were as effective in achieving control as 5500-6000 or 6000-7000 cGy.

Primary malignant lymphoma of the mandible.

From 1945 through 1985, 32 cases of primary lymphoma of bone were treated at the University of Iowa Hospitals and Clinics. Sixteen cases (50%) demonstrated the lesion in the long tubular bones with a predilection for the lower and upper extremities. The frequently involved flat bones (six cases) were the bones of the pelvis. There were only three cases (9%) where the mandible was the primary site. In this report, the literature is reviewed and three cases with primary lymphoma of the mandible are presented.

Chemodectoma of the temporal bone: a comparison of surgical and radiotherapeutic results.

Between January 1950 and December 1981, 32 patients with chemodectomas of the temporal bone were treated at the University of Iowa Hospitals and Clinics. Thirteen patients were treated with surgery alone, 15 with radiation therapy alone, one with preoperative radiation therapy and surgery, and three with surgery and postoperative radiation therapy. In general, the patients treated with radiotherapy alone or combined therapy (radiotherapy group) had more advanced tumors than those treated with surgery alone (surgery group). For the surgery group, the initial local control rate was 46% and the ultimate local control rate 84% following salvage with additional surgery, 31% developed complications, and 78% survived 10 years. For the radiotherapy group, 84% had local tumor control, 11% developed complications, and 77% survived 10 years. These results demonstrate that radiation therapy is an effective treatment modality for chemodectomas of the temporal bone.

Inoperable adenocarcinoma of endometrium: radiation therapy.

Between 1960 and 1979, 41 patients with adenocarcinoma of the endometrium who were poor surgical risks were treated with radiation therapy at the University of Iowa. Local tumor control was achieved in 78% of the patients, 5% manifested complications, and 46% survived 5 years ("uncorrected" 5-year survival rate). Intercurrent disease was the major cause of death (54%), and intrauterine recurrence (22%) was the most frequent recurrence. Intraperitoneal spread (12%) occurred as commonly as hematogenous metastases (12%). Three of nine local failures occurred after 5 years. Local control rates correlated well with clinical stage, and the survival rates correlated well with the stage and grade of the tumor. Local tumor control was achieved in 95% of patients who received greater than 7,000 mg-h intracavitary radium, compared with 63% of patients treated with less than 7,000 mg-h.

The use of interstitial radiation therapy in the treatment of persistent, localized, and unresectable cancer in children.

Two children with cancer that persisted after multiple exploratory laparotomies, external beam radiation therapy, and multidrug chemotherapy had gold 198 (198Au) seeds implanted into their localized but unresectable tumor. Both children are alive, are receiving no therapy, and are disease-free more than 2 years later. These two cases indicate the value of interstitial implant therapy in the treatment of some children with cancer.

Radiotherapy for pure seminoma of the testis.

Testicular tumors initially diagnosed as pure seminoma were irradiated following orchiectomy in 141 patients. Analysis of treatment failures reveals that (a) 2500 rads is adequate for elective irradiation and 3500 rads for small to moderate-size metastases; (b) elective irradiation of the mediastinum and left supraclavicular area is not indicated for Stage I, but is for Stage II; (c) patient with bulky retroperitoneal disease should be treated initially through total abdominal portais followed by additional treatment through reduced fields; and (d) presence of embryonal carcinoma, teratocarcinoma, or choricarconoma should be considered when regression is poor.