Mary Ann Hederman

Radiation therapy alone in the treatment of carcinoma of the uterine cervix: A 20-year experience

A retrospective analysis is reported on the results of irradiation alone in the treatment of 970 patients with histologically proven invasive carcinoma of the uterine cervix. The development of the radiation therapy techniques, survival, pelvic tumor control, and major sequelae of therapy are described in detail. The tumor-free 5-year survival rate was 100% in 29 patients with stage IA, 85% in 312 cases with stage IB, 70% in 98 patients with stage IIA, 68% in 276 patients with stage IIB, 45% in 237 stage III cases, and one survivor in 18 stage IV patients. No pelvic recurrences or distant metastases were observed in stage IA patients. In stage IB the overall incidence of pelvic recurrences was 7.3%, in stages IIA and IIB 14%, and in stage III 37%. Distant metastases were noted in 13% of the patients with stage IB, 22% of those with stages IIA and IIB, and 32% of patients with stage III tumors. Higher doses of irradiation delivered with intracavitary insertions and extenal beam were correlated with a lower incidence of pelvic recurrences in stages IIA, IIB, and III. However, doses to point A over 7000 cGy did not improve pelvic tumor control in stage IB. Grade 2 treatment sequelae were observed in about 10% of all patients and grade 3 complications in approximately 4% of the patients with stage I and 8% in those with more advanced tumors (IIA and beyond). The need is emphasized to carefully evaluate the dosimetric aspects of new techniques, including phantom studies before they are applied to patients. A close integration of external and intracavitary irradiation will result in better tumor control and fewer complications.

Role of irradiation in the management of superior vena cava syndrome

The records of 125 patients treated for superior vena cava syndrome secondary to malignant disease were reviewed retrospectively. The mean age of patients was 55 years. Bronchogenic carcinoma was the cause of the syndrome in 79% of cases, malignant lymphoma 18%, and other tumors 6%. Approximately 80% of the patients obtained good to excellent symptomatic relief. High initial dose radiation therapy (300-400 cGy daily for three fractions) yielded good symptomatic relief in less than 2 weeks in 70% of patients; conventional dose radiation therapy (200 cGy daily, five weekly fractions) yielded the same response in 56% of patients (p = 0.09). Lymphoma patients displayed a 1 year survival of 41%, small cell carcinoma 24%, and other types of bronchogenic carcinoma 17%. Combination of radiation and chemotherapy did not improve response rate, degree of symptomatic relief or long-term survival. Patients exhibiting symptomatic relief within 30 days had a significantly better survival rate than those who did not (p = 0.002). Thirteen percent of patients showed a recurrence of superior vena cava syndrome. There was no correlation between tumor regression and symptomatic relief. Side effects of therapy were minimal; dysphagia was the most common complaint (26% of patients).

Analysis of pelvic tumor control and impact on survival in carcinoma of the uterine cervix treated with radiation therapy alone.

A total of 1054 patients with histologically confirmed invasive carcinoma of the uterine cervix were treated with radiation therapy alone between 1959 and 1982. All patients are available for a minimum of 3 years follow-up. Radiation therapy consisted of external irradiation to the whole pelvis (1000-2000 cGy) and parametria (for a total of 4000-6000 cGy) combined with two intracavitary radioactive source insertions (6000-7500 cGy to point A). Patients with Stage IIB, III, and IVA have been consistently treated with somewhat higher doses of external irradiation and intracavitary insertions. A small group of 54 patients with Stage IIB or IIIB had pelvic lymphadenectomy following the irradiation (1960-1964). There was a strong correlation between the tumor regression within 30 days from completion of radiotherapy and the incidence of pelvic recurrences or distant metastases for each of the anatomical stages. The 10-year survival rate for Stage IB was 76%, Stage IIA 60%, Stage IIB 45%, and Stage III 25%. Many of the deaths were due to intercurrent disease. Thus, the 10-year tumor-free survival was 80% for Stage IB, 60% for Stages IIA and IIB and 35% for Stage III. In Stage IB total doses of 6000 cGy or higher to point A resulted in 94% pelvic tumor control. In Stage IIA, the pelvic tumor control was 87% with doses of 6000 cGy to point A or higher. However, in Stage IIB the pelvic tumor control was 58% with doses below 6000 cGy, 78% with 6001-7500 cGy and 82% with higher doses. In Stage IIIB the pelvic tumor control was 42% with doses below 6000 cGy, 57% with 6001-7500 cGy and 68% with higher doses. Tumor control in the pelvis was correlated with the following 5 year survivals: Stage IB-95% (353 patients); Stage IIA-84% (116 patients); Stage IIB-84% (308 patients); Stage IIIB-74% (245 patients). The 5-year survival for patients that recurred in the pelvis was 30% for Stage IB, about 15% for Stages IIA-B and only 5% in Stage III. Patients with tumor control in the pelvis had a significantly lower incidence of distant metastases than patients who initially failed in the pelvis (9.3% vs. 58.6% in Stage IB, 21.6% vs 52.6% in Stage IIA, 19.8% vs 16.7% in Stage IIB, and 31.2% vs 50% in Stage III). In Stage IIB the figures were 19.8% and 16.7% because the initial pelvic recurrence was frequently concurrent with distant metastases.(ABSTRACT TRUNCATED AT 400 WORDS)

Definitive irradiation in carcinoma of the vagina: Long-term evaluation of results

A retrospective analysis of 165 patients with histologically confirmed carcinoma of the vagina is reported. Actuarial disease-free 10-year survival was: Stage 0 (16 patients)--94%, Stage I (50 patients)--75%, Stage IIA (49 patients)--55%, Stage IIB (26 patients)--43%, Stage III (16 patients)--32%, Stage IV (8 patients)--0%. All but one of the in situ lesions were controlled with intracavitary therapy. Of the patients with Stage I disease, 86% showed no evidence of vaginal or pelvic recurrence. Most of them received interstitial or intracavitary therapy or both; the addition of external beam irradiation did not significantly increase survival or tumor control. In Stage IIA (paravaginal extension) 61% of the tumors were controlled with a combination of brachytherapy and external beam irradiation. Ten of 16 Stage III tumors were controlled in the pelvis. Two of the patients with Stage IV disease had no recurrence in the pelvis with relatively high doses of irradiation. The total incidence of distant metastases was 16% in Stage I, 30.6% in Stage IIA, 46.1% in Stage IIB, 62% in Stage III, and 50% in Stage IV. The dose of irradiation delivered to the primary tumor or the parametrial extension was critical in achieving successful results. The incidence of grade 2-3 complications (12%) is correlated with the stage of the tumor and type of treatment given. More effective irradiation techniques including the optimization of dose distribution by judicious combination of external irradiation and interstitial brachytherapy will be necessary to enhance loco-regional tumor control. The high incidence of distant metastases underscores the need for earlier diagnosis and effective systemic cytotoxic agents if survival is to be significantly improved in these patients.

Adenocarcinoma of the uterine cervix: Lack of evidence for a poor prognosis

A retrospective analysis was performed to evaluate the prognostic significance of histologic type (epidermoid carcinoma versus adenocarcinoma) on local control of disease and on the development of distant metastatic disease in 1239 patients with carcinoma of the uterine cervix treated with radiation therapy alone or surgery and irradiation at the Radiation Oncology Center, Mallinckrodt Institute of Radiology (MIR), Washington University Medical Center, between 1959 and 1982. The 5-year disease-free survival (all stages combined) was 68.0% for 925 patients with epidermoid carcinoma compared to 64.9% for 79 patients with adenocarcinoma treated with irradiation alone (p = 0.34). There was no significant difference in the survival rate when epidermoid carcinoma and adenocarcinoma were compared after stratification by clinical stage except for stage III. The 5-year disease-free survival (all stages combined) was 73.4% for 213 patients with epidermoid carcinoma and 77.0% for 22 patients with adenocarcinoma treated with irradiation plus surgery (p= 0.74). Prognostic variables analyzed by multivariate analysis included age at diagnosis, histology, size of lesion, endometrial extension, lymph node status (as evaluated by lymphangiogram), dose to point A, and surgery. Prognostic variables that were significant (p less than 0.05) for the development of recurrent disease in the pelvis were size of the primary lesion and dose of irradiation to point A. Significant (p less than 0.05) factors for the development of distant metastatic disease were size of the primary lesion and metastatic lymph nodes at the time of diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Randomized study of preoperative radiation and surgery or irradiation alone in the treatment of Stage IB and IIA carcinoma of the uterine cervix: Final report

Abstract A prospective randomized study in selected patients with Stage IB and IIA carcinoma of the uterine cervix was carried out at Washington University between January 1966 and December 1979. Patients were randomized to be treated with (1) irradiation alone consisting of 1000 cGy whole pelvis, additional 4000 cGy to the parametria with a step wedge midline block, and two intracavitary insertions for 7500 mgh; or (2) irradiation and surgery, consisting of 2000 cGy whole pelvis irradiation, one intracavitary insertion for 5000–6000 mgh followed 2 to 6 weeks later by a radical hysterectomy with pelvic lymphadenectomy. A total of 40 patients with Stage IB and 16 with Stage IIA were randomized to be treated with irradiation alone. A similar group of 48 patients with Stage IB and 14 with IIA were randomized to the preoperative radiation and surgery group. The 5-year, tumor-free actuarial survival for Stage IB patients treated with radiation was 89% and with preoperative radiation and surgery 80%. In Stage IIA, the tumor-free actuarial 5-year survival was 56% for the irradiation alone group and 79% for the patients treated with preoperative radiation and radical hysterectomy. In the patients with Stage IB treated by irradiation alone only one pelvic failure combined with distant metastasis occurred, and 3 patients developed distant metastasis. In the 48 patients treated with combined therapy, there were six pelvic failures (12.5%) all combined with distant metastases and two distant metastases alone. In the 16 patients with Stage IIA treated with radiotherapy alone, there were four pelvic failures (all parametrial), three of them combined with distant metastasis. In the 14 patients treated with irradiation and surgery, two developed a pelvic recurrence, and one distant metastasis. In the preoperative radiation group, the incidence of metastatic pelvic lymph nodes was 6.3% in Stage IB and 7.1% in Stage IIA. Major complications of therapy in the patients treated with radiation alone (10%) consisted of one rectovaginal fistula, two vesicovaginal fistulas, and one rectal stricture. In the preoperative radiation group, three ureteral strictures and two severe proctitis-rectal strictures were noted (8%). The present study shows no significant difference in therapeutic results or morbidity for invasive carcinoma of the uterine cervix Stage IB or IIA treated with irradiation alone or combined with a radical hysterectomy and lymphadenectomy.

Thermoradiotherapy of malignant melanoma

From 1978 through February 1986, 49 measurable lesions in 18 patients with recurrent primary or metastatic malignant melanomas were treated with a combination of radiation therapy and hyperthermia. The primary sites were head and neck (eight), chest wall (two), pelvis (one), upper extremities (three), and lower extremities (35). Because of the length of the study, the dose and fractionation of radiation therapy varied (dose per fraction from less than 400 cGy to 800 cGy and a total dose of 2000 cGy to 6000 cGy). This variation was mostly dependent on the prior course of radiation therapy of these lesions. The hyperthermia technique used in these patients was superficial local microwave hyperthermia; a minority of patients were treated with ultrasound. Complete response was achieved in 29 lesions (59.2 per cent) and partial response in six lesions (12 per cent). In a separate analysis of 67 lesions with superficial malignant melanoma who were treated by radiation therapy alone, a 24 per cent complete response and a 34 per cent partial response were achieved. Detailed analyses are presented in regard to dose per fraction, total radiation dose, and the size of lesions.

Phase I/II study of treatment of locally advanced (T3T4) non-oat cell lung cancer with high dose radiotherapy (rapid fractionation): Radiation therapy oncology group study

The Radiation Therapy Oncology Group (RTOG) completed a pilot study to test the feasibility of high dose of radiation therapy and its impact on tumor control and survival. From April 1, 1983 through May 1985, a total of 56 patients were treated on this protocol. All patients had locally advanced disease without distant metastases. The treatment regimen consisted of delivering 7500 cGy in 28 fractions over 5.5 weeks to the tumor, while the nodal bearing areas received 5040 cGy in the same period (daily dose to the mediastinum was 180 cGy; daily dose to gross tumor was 268 cGy). This is a considerably higher dose, with a TDF of 142 compared with a TDF of 92 (conventional fractionation of 6000 cGy in 6 weeks), which is the highest dose used in previous RTOG studies. Doses in this protocol (7500 cGy) was corrected for lung transmission whereas doses in prior RTOG protocols (6000 cGy) were uncorrected. Thus, after correction dose of 6600 cGy was calculated and coded for comparison. All short-term toxicities were acceptable, and the only major toxicity was one third-degree esophagitis in a patient with a follow-up of 12 months. Forty-four out of fifty-six patients received prescribed dose of irradiation. There were 17 complete responders and 15 partial responders, with an overall response rate of 32 out of 44 (72.7%). At the time of this report, there were 9 patients alive (NED); 5 died without tumor; and the remainder died of tumor or unknown.

Mini-colpostats in the treatment of carcinoma of the uterine cervix.

Between 1976 and 1982, 293 patients were treated for carcinoma of the uterine cervix at Washington University by definitive radiotherapy consisting of external beam therapy and two standard Fletcher-Suit applications (tandem plus vaginal colpostats). In ninety-nine patients (34%) mini-colpostats (MC) were used for one or both of their intracavitary insertions while 194 (66%) patients were treated twice with regular Fletcher-Suit colpostats (RC). The frequency of MC use was related to the age and parity of the patients. The distribution by stage of MC and RC groups was not significantly different. Pelvic failure in the MC group was similar to that of the RC group (21% vs 24%). Five-year disease-free survival was also similar between the two groups: 86% vs 80% Stage IB, 57% vs 61% Stage IIA, 47% vs 52% Stage IIB, and 27% vs 45% Stage III for MC and RC groups, respectively. The rate of major complications (grade 3) was 15% in the MC group and 8% in the RC group (p = 0.08). Careful phantom dosimetric studies in both types of colpostats and correlations of dose distributions at various points in the pelvis with frequency of rectal and bladder complications were carried out. The bladder and rectum received a 5-10% higher mean radiation dose (Gy) in the MC group than in the RC group despite lower overall exposure (milligram-hours). Thermoluminescent dosimetry in a polystyrene phantom demonstrates that approximately 10% higher doses are delivered to the bladder, rectum, and point A with an MC system as compared to an RC system, for constant exposure in mgh. Phantom measurements of a newer MC with bladder and rectal shielding demonstrate no influence on the bladder and rectal point dose at a source separation of 3 cm; midline points of the bladder and rectum are not within the full shadow of the shields even if the colpostats are flush with the tandem. Implications for therapy are discussed.

Randomized Study of Preoperative Radiation and Surgery or Irradiation Alone in the Treatment of Stage IB and IIA Carcinoma of the Uterine Cervix: Final Report

A prospective randomized study in selected patients with Stage IB and IIA carcinoma of the uterine cervix was carried out at Washington University between January 1966 and December 1979. Patients were randomized to be treated with irradiation alone consisting of 1000 cGy whole pelvis, additional 4000 cGy to the parametria with a step wedge midline block, and two intracavitary insertions for 7500 mgh; or irradiation and surgery, consisting of 2000 cGy whole pelvis irradiation, one intracavitary insertion for 5000-6000 mgh followed 2 to 6 weeks later by a radical hysterectomy with pelvic lymphadenectomy. A total of 40 patients with Stage IB and 16 with Stage IIA were randomized to be treated with irradiation alone. A similar group of 48 patients with Stage IB and 14 with IIA were randomized to the preoperative radiation and surgery group. The 5-year, tumor-free actuarial survival for Stage IB patients treated with radiation was 89% and with preoperative radiation and surgery 80%. In Stage IIA, the tumor-free actuarial 5-year survival was 56% for the irradiation alone group and 79% for the patients treated with preoperative radiation and radical hysterectomy. In the patients with Stage IB treated by irradiation alone only one pelvic failure combined with distant metastasis occurred, and 3 patients developed distant metastasis. In the 48 patients treated with combined therapy, there were six pelvic failures (12.5%) all combined with distant metastases and two distant metastases alone. In the 16 patients with Stage IIA treated with radiotherapy alone, there were four pelvic failures (all parametrial), three of them combined with distant metastasis. In the 14 patients treated with irradiation and surgery, two developed a pelvic recurrence, and one distant metastasis. In the preoperative radiation group, the incidence of metastatic pelvic lymph nodes was 6.3% in Stage IB and 7.1% in Stage IIA. Major complications of therapy in the patients treated with radiation alone (10%) consisted of one rectovaginal fistula, two vesicovaginal fistulas, and one rectal stricture. In the preoperative radiation group, three ureteral strictures and two severe proctitis-rectal strictures were noted (8%). The present study shows no significant difference in therapeutic results or morbidity for invasive carcinoma of the uterine cervix Stage IB or IIA treated with irradiation alone or combined with a radical hysterectomy and lymphadenectomy.