B-Chen Wen

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.

Hemangiopericytoma--the role of radiotherapy.

Between 1955 and 1987, 15 patients with hemangiopericytomas were seen at the University of Iowa Hospitals and Clinics. Twelve of these were thought to have localized tumors and three had metastatic disease at diagnosis. Seven of the 12 patients with localized disease were treated with surgery alone, four were treated with surgery and postoperative radiation therapy, and one was treated with surgery and chemotherapy. Only one of the seven patients initially treated with surgery alone has remained continuously free of disease, although two others were salvaged with radiation therapy. In contrast, all four patients initially treated with surgery and postoperative radiation therapy have remained alive with no evidence of disease in spite of the fact that three of these patients had gross residual tumor at the time of irradiation. Ten patients received radiation therapy at some stage of their management. Local tumor control was achieved at all sites receiving greater than 5500 cGy. Six patients received chemotherapy sometime during the course of their management, although no complete or partial responses were observed. In this small series, mitotic activity was not an accurate predictor of biologic behavior.

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.

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.

The significance of radiotherapy treatment duration in intracranial ependymoma

PURPOSE To determine if radiation therapy treatment duration has an impact on the outcome of intracranial ependymoma. METHODS AND MATERIALS From 1965 to 1997, 34 patients with intracranial ependymoma were seen and treated with postoperative radiotherapy (RT). There were 26 male and 8 female patients with a median age of 14 years (range, 18 months to 60 years). Tumor location was infratentorial in 23 (67.6%) and supratentorial in 11 (32.4%). Pathology was low-grade in 25 (73.5%) and high-grade in 9 (26.5%). Two (5.9%) patients had M+ disease at initial diagnosis. Gross total resection was achieved in 12 (35.3%), subtotal resection in 19 (55. 9%), and biopsy alone in 3 (8.8%). Median RT dose to the primary site was 5400 cGy (range, 4500 cGy to 6600 cGy). The entire neuraxis was treated in 14 (41.2%), whole brain in 9 (26.5%), and the primary site alone in 11 (32.4%). Median radiotherapy treatment duration was 43 days (range, 26 to 122 days). Patients treated with craniospinal RT were more likely to have treatment duration of > or =50 days. Median follow-up was 108 months (range, 24 to 252 months). RESULTS The 5-, 10-, and 15-year overall survival rates were 71.5%, 63.3%, and 55.4%. Local control rates at 5, 10, and 15 years were 61.8%, 57.7%, and 57.7%. For patients with RT treatment duration <50 days, the 5-, 10-, and 15-year overall survivals were 85.5%, 78.9%, and 65.7% whereas for those with treatment duration > or = 50 days, the corresponding rates were 45.5%, 36.4%, and 36.4% (p = 0.01, log-rank test). Local control rate at 5, 10, and 15 years was 70.6% for patients with RT treatment duration <50 days and 45.5%, 36.4%, and 36.4% for patients with RT treatment duration > or =50 days (p = 0.05, log-rank test). Age, gender, tumor location, tumor grade, degree of surgical resection, RT volume, and RT dose (4500-5399 cGy vs. 5400-6600 cGy) were not found to have a statistically significant impact on overall survival, disease-free survival, or local control. The most common site of failure was local, found in 13 (38.2%) patients. Three patients also had spinal failure in addition to a primary site failure. There were no isolated nonprimary site brain or spine failures. CONCLUSIONS Radiation therapy treatment duration is an important prognostic factor for survival and local control with patients having treatment duration <50 days having a better outcome than those with treatment duration > or =50 days. Because the overwhelming site of failure was local, we recommend local field irradiation in patients with M0 disease.

RADIATION THERAPY DURING PREGNANCY

Malignant disease requiring radiation therapy during pregnancy presents an enormous challenge for the clinician. The optimal radiotherapeutic management of the patient and the optimal management of the pregnancy involve directly opposing demands. Ionizing radiation should be avoided during pregnancy whenever possible. Doses in excess of 0.1 Gy (10 rad) delivered during gestation have been associated with various detrimental effects, and therapeutic abortion has been recommended. If radiation is unavoidable, such as in the treatment of some gynecologic tumors, lymphomatous diseases, or other advanced solid tumors, it must be performed with extreme caution and maximal effort to reduce the dose to the fetus by special shielding techniques. Decisions regarding the use of radiation therapy during pregnancy, the delay of therapy, or pregnancy termination should be made by a multidisciplinary team and be guided by the prognosis of the disease, the stage of gestation, the risk to the fetus from the expected fetal radiation dose, and the patients ethical and religious beliefs.

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.

Donor T-lymphocyte infusion for unrelated allogeneic bone marrow transplantation with CD3+ T-cell-depleted graft

Summary:In T-cell-depleted allogeneic bone marrow transplantation (TCD-BMT) using unrelated donors, the role of donor lymphocyte infusion (DLI) for survival and disease control has not been defined. In a study of 116 patients (92 matched, 24 mismatched) who received CD3+ T-cell-depleted marrow graft, sequential infusions of escalated doses of donor T lymphocytes up to 1×106 CD3+ cells/kg were prospectively investigated. T cells were administered while patients were on cyclosporine, provided ≥grade II acute graft-versus-host-disease (GVHD) had not occurred. Acute GVHD of ≥grade II occurred in 27 of 110 (25%) patients before DLI and in 39 of 79 (49%) patients after DLI. In total, 12 of 27 (44%) patients without DLI and 44 of 72 (61%) patients who received DLI developed chronic GVHD. A total of 19 patients died of GVHD, with 17 of acute and two of chronic GVHD. Overall survival (OS) and event-free survival (EFS) at 5 years were 27 and 21%, respectively. The 2-year incidence of relapse was 14%. In multivariate analysis, only chronic GVHD was a good prognostic factor for both OS: hazard ratio (HR) 1.4, P=0.04, and EFS: HR 1.6, P=0.01. Both acute and chronic GVHD were favorable prognostic factors for relapse probability: HR 1.9 for both, P=0.02, 0.01, respectively. The 1-year cumulative incidence of transplant-related mortality (TRM), excluding cases of GVHD, was 42%. The two most common causes of 1-year non-GVHD death were viral infection (9%) and idiopathic pneumonia syndrome (12%). Although the incidence of relapse was low, the study suggests that the current scheme of DLI in unrelated TCD-BMT would not improve survival unless TRM decreases significantly.

Prophylactic T cell infusion after T cell-depleted bone marrow transplantation in patients with refractory lymphoma.

Fifty-two patients with refractory lymphoma were prospectively treated with prophylactic T lymphocyte infusion after T cell-depleted allogeneic bone marrow transplantation, to induce graft-versus-lymphoma effect. Thirty-three patients had related donors; 19 had unrelated donors. After transplantation with marrow that had 0.8 ± 0.4 × 105CD3+ cells/kg, T cells up to 1.75 × 106 CD3+ cells/kg were given over 3 months provided ⩾ grade II acute graft-versus-host disease (GVHD) was not seen. The cumulative incidence of grades II–IV acute GVHD was 69%. Twenty of 32 evaluable patients (63%) developed chronic GVHD. Ten patients (19%) died of GVHD. The Kaplan–Meier 5-year overall survival of all patients was 34%. On multivariate analyses, chronic GVHD was significant for relapse (hazard ratio of 1.7, P < 0.05), and for overall survival (hazard ratio 1.4, P < 0.001). Chemosensitivity was significant for relapse only on univariate analysis. Patients who developed chronic GVHD had 4 years median survival, compared with 9 months in patients without chronic GVHD, P < 0.001. The study shows that patients with chronic GVHD have superior survivals, most probably related to a graft-versus-lymphoma effect, which could be modulated by prophylactic T cell infusion.