John J. Staples

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.

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.

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.

Morphometric studies in intraductal breast carcinoma using computerized image analysis

A morphometric study was performed using computerized image analysis on the histologic specimens of 26 patients with intraductal carcinoma of the breast and 26 normal control patients. A significant incidence of necrosis (56%) was observed in the breast ducts containing intraductal carcinoma. This was characterized by one or more areas of necrosis surrounded by a rim of viable tumor cells. The mean diameter of the ducts containing intraductal carcinoma was 349 μm compared with a mean diameter of 90 μm for the normal ducts. The mean diameter of the ducts containing necrosis was 470 μm compared with a mean diameter of 192 μm for the ducts containing a solid pattern of intraductal carcinoma. Central necrosis occurred in 94% of the ducts more than 180 μm in radius, whereas only 34% of the ducts less than 180 μm in size contained necrosis. The width of the viable neoplastic tissue was less than 180 μm in 91% of the ducts. These results are analogous to the findings of Thomlinson and Gray in human lung tumor cords and provide indirect evidence for the existence of a hypoxic compartment in intraductal carcinoma of the breast. This could be an explanation for the higher local failure rate after conservative surgery and irradiation for infiltrating cancers containing an extensive intraductal component.

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.

Intraductal Breast Carcinoma: Initial Results of a Morphometric Study Using Computerized Digital Image Analysis

Extensive ductal carcinoma in situ (DCIS) and necrosis in breast carcinoma have been correlated with a higher incidence of local recurrence in patients treated with breast-conserving surgery and radiotherapy. In an attempt quantitatively to assess duct size distribution and necrosis in DCIS, the authors devised a method utilizing computerized digital image analysis. The method and results of a pilot study comparing 21 patients with DCIS, and 21 normal breast specimens are presented. Normal breast tissue from autopsy material revealed a mean duct diameter of 90 microns, whereas the mean diameter of ducts in patients with DCIS was 359 microns (P less than 0.001). The presence of necrosis in DCIS correlated strongly with average duct size. Of the ducts larger than 360 microns in diameter 94% exhibited intraductal necrosis, whereas ducts less than 360 microns showed necrosis in only 30% of the measurements. Ducts with necrosis revealed a mean diameter of 498 microns versus 198 microns in ducts without necrosis (P less than 0.001). The authors suggest that necrosis develops in response to tumour cell hypoxia associated with cross-sectional duct expansion in DCIS. This growth pattern predisposing to tumour cell hypoxia could be a factor contributing to radioresistance and increased local recurrence.

A Simple Method for Reducing Ovarian Dose During Megavoltage Irradiation of the Breast

Breast cancer in its early stages can be effectively treated with conservative surgery and irradiation. In young women who wish to subsequently bear children, reduction of ovarian dose during irradiation could be of great emotional significance. We describe a simple, convenient, cost-effective method by which ovarian dose was reduced from 18 cGy to 8 cGy during tangential irradiation of the intact breast with 6 MV photons.