John A. Stryker

Analysis of factors contributing to treatment failures in Stages IB and IIA carcinoma of the cervix

Between April, 1971, and September, 1977, 98 patients with Stages IB and IIA cervical cancer who underwent surgical exploration prior to treatment at Hershey Medical Center were studied. Those who had bulky primary tumor (greater than or equal to 4 cm) had a higher incidence of nodal metastases (80% vs. 16%), local recurrences (40% vs. 5%), and distant metastases (40% vs. 1%). Patients who had positive nodes had more local recurrences (24% vs. 6%) and distant metastases (28% vs. 0%). Those with grossly positive nodes had more distant metastases (60% vs. 7%) than those with microscopically positive nodes. Those who had positive nodes, vascular invasion, and/or deep invasion of the cervix (greater than or equal to 70% of thickness) in the radical hysterectomy specimen had more nodal metastases and local recurrences. Postoperative radiation seemed to prevent local recurrences (40% vs. 6%) and improve the 2-year tumor-free survival rate (94% vs. 55%). Patients who had bulky primary tumors and/or grossly positive nodes at laparatomy may require systemic therapy in view of the high incidence of distant failures.

Detection and patterns of treatment failure in 300 consecutive cases of “early” endometrial cancer after primary surgery

From November 1977 to July 1987, 300 consecutive patients with endometrial carcinoma clinically confined to the uterine corpus underwent primary surgery consisting of at least abdominal hysterectomy and adnexectomy. Patients with aggressive disease characteristics received postoperative radiotherapy. Forty-seven patients (16%) demonstrated recurrent disease from 2 to 125 (median of 12.8) months after surgery. Forty-seven percent of the recurrences were detected within the first year following surgery and 70% by 2 years after hysterectomy. Of the 47 recurrences, 29 were at distant sites, 16 were within the pelvis, and 2 consisted of both local and distant recurrences. Patients treated with pelvic radiotherapy after hysterectomy were more likely to experience distant, rather than local recurrences. Only 7 of the 148 patients (5%) treated with postoperative radiotherapy recurred in the pelvis. Approximately half of the recurrences were detected in asymptomatic individuals; physical examination and chest X-ray were the most useful means to detect disease in patients without symptoms. The combination of history, physical examination, pap smear, and chest X ray detected all of the recurrences. Actuarial survivals at 12, 24, and 36 months after recurrence were 42, 24, and 17%, respectively. The site of recurrence, time interval of surgery to recurrence, and use of postoperative pelvic radiotherapy were statistically related to patient prognosis. The identification of patients at risk of recurrence and more effective adjuvant therapy need to be developed in order to decrease the frequency of recurrence. In order to substantially improve the survival of patients with recurrent disease, more sensitive methods of detection, as well as more effective salvage therapy, will be required.

Bladder and rectal complications following radiotherapy for cervix cancer

One-hundred and thirty-two patients with cervix carcinoma who were treated with whole pelvis irradiation and two intracavitary applications had bladder and rectal dosimetry during brachytherapy with contrast agents placed into the bladder and rectum prior to orthogonal simulator radiographs. Doses were computer calculated at points A and B, F (bladder), R1 (rectum), and R2 (rectosigmoid). Late occurring bladder and rectal complications were graded on a severity scale of 1 to 3, and 14% had grade 2 or 3 injuries (9% developed fistulas). Statistical evaluation of the data showed that severe bladder and rectal injuries occur more commonly in stage IIIA and IIIB disease and in those receiving high external beam doses (5000 rad +). Analysis of variance tests revealed a significant correlation of brachytherapy dose to points R1 and R2 with severe rectal injuries but there was not a correlation of dose to F with bladder injuries. Nor was there correlation of injuries with dose to point A or the milligram-hour dose. We conclude that our technique for rectal dosimetry is adequate but that an improved technique of bladder dosimetry is needed. Also, when combining whole pelvis irradiation with two intracavitary applications (4000 rad to point A), the whole pelvis dose should probably not exceed 4000-4500 rad.

Glioblastoma multiforme following prophylactic cranial irradiation and intrathecal methotrexate in a child with acute lymphocytic leukemia.

Cases of radiation‐induced glioma in humans are extremely rare. A 2‐year‐old boy with acute lymphocytic leukemia had received prophylactic cranial irradiation (2400 rad/2 1/2 weeks) and intrathecal methotrexate. Five years later he developed a glioblastoma multiforme on the left cerebral hemisphere while the leukemia was in remission. This is the first reported association of these disorders. It is possible that the glioma may have been induced by radiation and/or chemotherapy.

Routine clinical estimation of rectal, rectosigmoidal, and bladder doses from intracavitary brachytherapy in the treatment of carcinoma of the cervix☆

Abstract An evaluation of rectal, rectosigmoidal, and bladder doses from intracavitary brachytherapy in carcinoma of the cervix has been initiated on a routine basis in an effort to obtain the optimum radiotherapeutic dose. Contrast radiography on a radiotherapy simulator is used to image the rectum and bladder, and dose rates are determined at predesignated reference points with the aid of computer calculated dose distributions. Forty-three patients have been reviewed in order to ascertain the correlation between radiation injury and dose at reference points in the rectum and bladder. The variability in the incidence of injury and the importance of predisposing factors suggests that a single tolerance dose for the reference points is not satisfactory. However, the reference doses are an important addition to other clinical factors in evaluating the treatment plan. Further, the reference doses can alert the therapist to the presence of hot spots resulting from unusual anatomy or perforation of the uterus. Finally, they serve as documentation of the doses to normal structures within the treatment volume. This is an important aspect of current radiotherapy. In a related study involving 77 patients, the doses at points A and B and the prescription in mghr were analyzed in relation to radiation injury. There was no apparent association between the incidence of radiation injury in either the mghr prescription or the doses at points A or B. Computer calculations were supplemented with in vivo and in vitro thermoluminescent dosimeter (TLD) measurements. The in vivo rectal measurements are of little value on a routine basis because of the difficulties in obtaining the measurements and the uncertainties in the measured values. We conclude that routine contrast radiography of the rectum and the bladder with dose calculations at selected reference points provides important information for optimizing radiotherapy in carcinoma of the cervix without a significant increase in treatment planning effort or patient discomfort.

Carcinoma of the Lung: Evaluation of Histological Grade and Factors Influencing Prognosis

The results in 96 patients with lung cancer who underwent lobectomy or pneumonectomy were analyzed. In reviewing the case histories of these patients, it became apparent that those with poorly differentiated tumor (grade 3) have an increased likelihood of positive lymph node metastases compared with those with well-differentiated (grade 1) or moderately differentiated (grade 2) tumor. Poor differentiation of the tumor, vascular invasion, and lymph node metastases appear to represent poor prognostic indices in patients undergoing operation. Compared with patients with grade 1 and grade 2 tumors, patients with a grade 3 adenocarcinoma had more local recurrences, while those with grade 3 squamous cell carcinoma had more distant metastases. The findings suggest that histological grading is an important adjunct to the clinical evaluation of and planning of treatment for patients with lung cancer.

Extended‐field radiation therapy for carcinoma of the cervix

The survival of cervical carcinoma patients with paraaortic/high common iliac nodal metastases was evaluated by retrospective chart review during a 13‐year interval. Thirty‐three patients with cervical carcinoma and surgically documented nodal metastases received primary, extended‐field radiation therapy. Overall 2‐year and 5‐year actuarial survival rates after diagnosis were 37% and 31%, respectively. Survival was analyzed in terms of the variables patient age, clinical stage, tumor histologic type, the presence of enlarged paraaortic/high common iliac lymph nodes, the extent of nodal involvement (microscopic versus macroscopic), the presence of intraperitoneal disease, and whether intracavitary brachytherapy was administered. The use of intracavitary radiation therapy was associated with improved local control and survival (P = 0.017). None of the other variables were statistically related to patient survival. Twenty‐two of the patients died of cervical cancer and five are surviving without evidence of cancer. Four patients died of intercurrent disease. Two patients developed bowel‐related radiation complications; both patients received chemotherapy concurrent with the radiation therapy. One of the two patients died of radiation enteritis. The use of extended‐field radiation therapy does benefit a small group of patients and may result in extended patient survival.

Evaluation of adjuvant postoperative radiotherapy lung cancer

One hundred eighteen patients with lung cancer were retrospectively analyzed to determine whether postoperative radiotherapy (RT) improves survival. Patterns of treatment failure and three year NED (no evidence of disease) survival rates were assessed according to extent of tumor spread, histology, and treatment method. Patients with hilar or mediastinal node metastases were at higher risk of local failure compared to those with negative nodes. Postoperative RT reduced local recurrence and improved 3 year survival among patients with positive nodes. However, postoperative RT did not improve survival among those with negative nodes. Our data indicated that patients with positive hilar or mediastinal nodes may require postoperative RT to improve survival.

Histologic grade and lymph node metastasis in squamous cell carcinoma of the cervix

One hundred fifty-nine patients with squamous cell carcinoma of the cervix who underwent laparotomy were evaluated with regard to histologic grade, clinical stage, and surgical stage. Pelvic and/or paraaortic node metastases were also studied. Patients with poorly differentiated tumors, regardless of clinical stage, demonstrated pelvic and/or paraaortic nodal metastases more frequently than patients with better differentiated tumors. In patients with poorly differentiated tumors, staging discrepancies were more common. These findings suggest that histologic grading should be taken into consideration in the treatment planning of patients with cervical carcinoma.

The Effect of Pelvic Irradiation on Ileal Function

Thirty-three patients with gynecological neoplasms undergoing radiotherapy to the pelvis had cholyl[1-14C]glycine breath tests to assess ileal function. Breath tests were performed on each patient in the first and fifth weeks of treatment and 19 of the patients had a third test three months post-treatment. In the first test, 29.9+/-16.8% (mean+/-SD) of the administered dose was excreted in breath 14C in 24 hours. This rose to 47.3+/-15.9% (t=6.08; p less than .001) in the fifth week and fell to 36.6+/-16% (t=2.29; p less than .05) at three months post-treatment. Eight patients had breath tests performed one year post-treatment and the test percentages were 32.7+/-7.8% (t=1.19; p less than .10). The increase in 14CO2 excretion in the fifth week of treatment occurred at a time when most patients were having diarrhea. The data suggest that bile acid malabsorption due to ileal dysfunction may be a factor in radiation-induced diarrhea which occurs in nearly all patients during pelvic irradiation.