Sherry Breaux

Radiation therapy alone in the treatment of carcinoma of the uterine cervix. II. Analysis of complications

A retrospective analysis was carried out on 811 patients with histologically proven invasive carcinoma of the uterine cervix treated with irradiation alone. A correlation was made of the doses of irradiation delivered to the pelvic organs with external beam and intracavitary insertions. Approximately 3% of the patients exhibited grade 2 gastrointestinal complications, and 2% developed grade 2 urinary complications; 5% of the patients developed grade 3 gastrointestinal complications, and 3% developed grade 3 urinary complications. Other types of complications, primarily grade 2, such as vaginal necrosis, pelivic abscess, thrombophlebitis, etc, were seen in approximately 5% of the patients. Thus, the total percentage of patients developing grade 2 complicatins was 10% and grade 3 complications, approximately 8%. About 25% of the patients who had complications showed more than one sequela. The most frequently observed grade 2 complications were proctitis, cystitis, vaginal stenosis, and partial small bowel obstruction which were treated with conservative management. Grade 3 complications required surgical treatment and consisted most frequently of ureteral stricture, vesicovaginal fistula, rectovaginal fistula, sigmoid stricture, small bowel obstruction, proctitis, and large rectal ulcers. The most significant factor affecting the appearance of complications was the total dose of irradiation delivered to the pelvic organs by the whole pelvis external irradiation and intracavitary insertions. With maximum total doses up to 8000 rad the incidence of grade 2 and 3 complications was less than 5%. However, with higher doses the incidence of complications increased to 10% to 15%. In patients receiving total doses of 6000 rad to the bladder or rectum, more complications were noted when only one intracavitary insertion was performed, as compared with two or three. Eighty percent of the rectosigmoid complications occurred within 30 months of initial therapy, in contrast to 48 months for the urinary complications. Patients who developed complications had survival rates comparable to those without complications. This underscores the need to rapidly institute treatment on patients who have severe injury after radiation therapy. Even though it is difficult to determine the exact total dose delivered to a specific volume within the pelvis, the current study strongly indicates that dose calculations to specific anatomical points may be reliable parameters to use in modifying treatment techniques to deliver doses of irradiation that will not exceed tolerance limits for the pelvic structures, when treating patients with carcinoma of the uterine cervix with irradiation alone.

Radiation therapy alone in the treatment of carcinoma of uterine cervix I. Analysis of tumor recurrence

This is a retrospective analysis with emphasis on the patterns of failure in 849 patients with histologically proven invasive carcinoma of the uterine cervix treated with irradiation alone. In 281 patients with Stage IB tumors, the total incidence of pelvic failure was 6.4% (two without and 16 combined with distant metastasis). In 88 patients with Stage IIA, 12.5% failed in the pelvis (one without and ten combined with distant metastasis). The total pelvic failure rate in Stage IIB was 17.4% (22 without and 22 combined with distant metastasis). In 212 patients with Stage III, the overall pelvic failure rate was 35.8% (31 without and 45 combined with distant metastasis). Approximately 25% of the pelvic recurrences were central (cervix or vagina) and 75% parametrial. The overall incidence of distant metastasis was 13.5% for Stage IB, 27.3% for Stage IIA, 23.8% for Stage IIB, and 39.6% in Stage III. Higher doses of irradiation delivered to the medial and lateral parametrium with external beam irradiation and intracavitary insertions were correlated with a lower incidence of parametrial failures in all stages, except IB. In Stage IIA, medial parametrial doses below 9000 rad resulted in 10/78 = 12.8% pelvic failures, in contrast to one recurrence in 10 patients treated with doses over 9000 rad. In Stage IIB, doses below 9000 rad yielded a pelvic recurrence rate of 36/203 (17.7%) compared to 5/49 (10.2%) with higher doses. In Stage III there were 66/167 (39.5%) recurrences with doses below 9000 rad and 10/44 (22.7%) with larger doses. Statistically significant differences were observed among the Stage IIB (P = 0.02) and III patients (P = 0.005) respectively. The lateral parametrial dose also showed some correlation with tumor control, although the differences were not statistically significant. The survival in patients with Stage IIB and III was 10% higher in the patients treated with higher parametrial doses. However, the differences are not statistically significant. These results strongly suggest that higher doses of irradiation must be delivered to patients with Stage IIB and III, but improvement in tumor control must be weighed against an increasing number of complications. Factors other than the total doses of irradiation, such as the characteristics of the tumor and the quality of the intracavitary insertion influence the therapeutic results in irradiation of carcinoma of the uterine cervix. Other therapeutic approaches must be designed to improve the effect of irradiation in the tumor without further injury to the normal tissues. Hypoxic cell sensitizers, hyperthermia and high LET particles are under investigation.

Carcinoma of the tonsillar fossa. A nonrandomized comparison of preoperative radiation and surgery or irradiation alone: Long-term results

The characteristics and results of therapy in 218 patients with histologically proven epidermoid carcinoma of the tonsillar fossa are reported. Ninety‐eight patients were treated with irradiation alone (5500–7000 rad). One hundred twenty patients were treated with preoperative radiation (2000–3000 rad) and en bloc radical tonsillectomy with ipsilateral lymph node dissection. The actuarial three year survival on patients with T1 tumors was 76%; T2, 40%; T3, 42%; and T4, 25%. The patients with no cervical lymphadenopathy or with a small metastatic lymph node (N1,N2) had better survival (50% at five years) than those with fixed lymph nodes (20%–30%). The primary tumor recurrence rate in the T1–T2 groups was about 20% in the patients treated with preoperative radiation and surgery in contrast to 35% to 40% for those treated with radiation alone. This difference is not statistically significant. The local recurrences in the patients with T3 lesions were 30% with both treatment groups; with T4 lesions recurrences noted in 50% of the patients receiving irradiation alone and 75% in the patients treated with preoperative radiation and surgery. The local recurrence rate in the neck was about 10% for the NO patients, 30% for N1, and 30% for the patients with N2 and N3 cervical lymph nodes. The incidence of contralateral recurrences was about 10% in the various primary tumor or lymph node stage groups. There was no significant difference in the survival or in the frequency of recurrences in the primary or neck in the patients treated with radiation alone or preoperative radiation and surgery. Fatal major complications were noted in eight of the 120 patients treated with preoperative radiation and surgery (6.6%) in contrast to only one in the 98 patients treated with radiation alone. Other less severe complications were noted in 40% of the patients treated with preoperative radiation and surgery and in 32.6% of those treated with radiation therapy alone. Radiation therapy remains the treatment of choice for patients with carcinoma of the tonsillar fossa. In selected cases a combination of both modalities may offer better tumor control, but the possibility of a higher complication rate must be considered.

Correlation between radiation dose and tumor recurrence and complications in carcinoma of the uterine cervix: Stages I and IIA

Abstract A retrospective analysis is reported on 330 patients with carcinoma of the uterine cervix, 23 with Stage IA, 233 with Stage IB and 74 with Stage IIA disease treated with irradiation alone. The dose of irradiation delivered to the cervix, paracervical tissues or the pelvic lymph nodes was correlated with tumor control. There were no central or parametrial failures in patients with Stage IA disease. There were 4 local or marginal (central) recurrences (1.6%) and 15 (6.5%) parametrial failures in the patients with Stage IB disease. Of 74 patients with Stage IIA disease, 3 developed cervical failures (3.9%) and 4 had both central and parametrial recurrences (5.2%). A definite correlation was found between the dose of irradiation delivered to the pelvic lymph nodes and the incidence of recurrences in the patients with Stage IB disease, (about 20%) parametrial failures with doses below 4000 rad in contrast to about 5% with 4000–5000 rad and 2% with doses over 6000 rad). Among patients with Stages IB and IIA disease, the survival of those who were treated with radiation alone and who received doses less than 4000 rad was about 10% less than patients who were treated with higher doses. This difference is not statistically significant; however, it suggests strongly that higher doses of irradiation to the parametria correlate with better tumor control in the pelvis and survival. Complications were slightly higher with doses to the bladder or rectum over 8000 rad. Although it was not statistically significant, patients who had non-standard intracavitary insertions had approximately 18% complications in contrast to only 6.6% in 135 patients with adequate insertions. Factors other than total dose of irradiation, such as geometry of the pelvis, characteristics of the tumor, position of the applicator, type of applicators used, loading and dose rate are important in evaluating the effects of irradiation in tumor control and complications of carcinoma of the uterine cervix.

Accrual of radiotherapy patients to clinical trials

Recruitment of patients to clinical trials is a multi‐stage process. To participate in a protocol, a patient must meet all the eligibility requirements; the physicians managing the patient must be amenable to enrolling the patient on protocol; and finally, the patient must consent to participate. In 1979, 64 clinical trials were open to patient accrual in the Division of Radiation Oncology, Mallinckrodt Institute of Radiology, St. Louis, Missouri. A total of 1103 cases were reviewed. Two hundred sixty‐three patients were eligible for one of the protocols, of whom 124 were successfully recruited. The reasons for ineligibility and nonparticipation are discussed.

Endometrial extension of carcinoma of the uterine cervix: A prognostic factor that may modify staging

A retrospective review was done of 473 patients with histologically proven primary carcinoma of the uterine cervix on whom a dilatation and curettage (D & C) was performed during the initial workup. The pathologic features of the D & C specimens were classified as: (1) endometrial stromal invasion of cervical carcinoma; (2) tumor only, cervical carcinoma in D & C, normal endometrium absent; (3) admixture of normal endometrium and cervical carcinoma (contamination); (4) D & C negative for tumor. The patients were staged according to the FIGO classification. Eighty‐two percent (388) of the patients were treated with radiation alone and the rest with a combination including surgical procedures (usually radical hysterectomy with lymphadenectomy). The three‐ and five‐year survival rates were 10% to 20% lower for patients with D & C showing stromal invasion or tumor only than in patients with admixture or negative D & C. These results were coupled with an appreciably higher number of distant metastases in the patients with positive D & C and a lower incidence in patients with negative D & C. The authors suggest that endometrial extension of carcinoma of the uterine cervix may be an important factor in the staging classification of these patients and recommend that D & C always be done in the initial evaluation. Because of the high incidence of distant metastasis, effective adjuvant therapy must be developed to improve the present therapeutic results.

Irradiation alone or in combination with surgery in stage IB and IIA carcinoma of the uterine cervix: A nonrandomized comparison.

This is a report of a nonrandomized comparison of treatment results of 244 patients with stage IB carcinoma of the uterine cervix treated by radiation alone and 92 treated with preoperative radiation and surgery and 77 patients with stage IIA treated by radiation alone and 24 treated with a combination of radiation and surgery. The techniques of irradiation and types of operation are described in detail. The five‐year tumor free actuarial survival for the patients with stage IB treated either with irradiation alone or combined with surgery was approximately 85% and the ten‐year survival, 78%. For stage IIA the tumor free actuarial five‐year survival without tumor was 73% and for ten years, 60%. In the 244 patients treated with radiation alone, there were ten central failures (4%) usually combined with distant metastasis. Further, 16 of these patients (6.5%) developed parametrial recurrence, in all but one instance associated with distant metastasis. In the 92 patients with stage IB treated with combined therapy, there were three local recurrences (3.8%), two of them combined with parametrial failures and six parametrial recurrences (6.5%), all of them concomitant with distant metastasis. Of the 77 patients with stage IIA treated by irradiation alone, there was one central recurrence alone and five local and parametrial recurrences, all of them associated with periaortic nodes or distant metastasis. Four additional patients had parametrial recurrences only concurrent with distant metastasis. Of the 24 patients treated with irradiation and surgery, there were two parametrial recurrences combined with distant metastasis (8.2%). There was no significant difference in the survival or recurrence rate of the patients treated with either method. In the group treated with combined therapy, patients with stage IB who showed evidence of microscopic residual tumor after irradiation had a failure rate of approximately 42% (8/18) in contrast to only 8.6% (6/70) in those with negative specimens. In stage IIA there were three failures in eight patients with residual tumor in the specimen in contrast to only two of 16 with negative specimens (12.5%). Major complications were comparable in both groups (radiation alone approximately 8.7% and irradiation combined with surgery approximately 14%), the difference is not statistically significant. The most frequent minor complication in patients treated with radiation alone was vaginal fibrosis (30 patients—9%) or vaginal vault necrosis (10 patients—3%). Cancer 43:1062–1072, 1979.

Pitfalls in the use of death certificates for assessing cause of death: a study of tonsil carcinoma patients.

A STUDY WAS UNDERTAKEN TO DETERMINE THE accuracy of underlying cause of death as stated on the death certificate for patients treated at Mallinckrodt Institute of Radiology (MIR) for carcinoma of the tonsil. The sample consisted of 110 patients who were treated between 1953 and 1976 and who subsequently died; all patients were seen by a physician within 3 months of their death. Death certificate cause of death was compared with the cause of death as stated in the MIR patient record. Death certificates detected 42.5% of the deaths due to tonsil carcinoma recorded in the hospital record, and detection was found to correlate with time between treatment and death. Of the deaths reported on the death certificate as due to tonsil carcinoma, 91% were confirmed by the hospital record to be correctly reported. Overall agreement in assignment of cause of death between the hospital record and the death certificate was 59%, and was significantly affected by stage of disease at diagnosis. This review underscores the low reliability of death certificates and raises a serious question concerning the use of this information for patients who are registered in clinical trials without additional documentation of tumor extent and cause of death.

34. The Need for Elective Irradiation of Occult Lymphatic Metastases from Cancers of the Larynx and Pyriform Sinus

The incidence of palpable and occult cancer and the absence of cancer in lymph nodes were determined for individual sites in the larynx and pharynx of 540 patients who underwent neck dissection. The incidence of palpable cancer in lymph nodes was lowest for cancers of the central supraglottis and transglottis (32-41%), intermediate for cancers of the marginal supraglottis and glossoepiglottis (48-57%), and highest for cancers of the pyriform sinus (69%). The incidence of occult cancer in lymph nodes for individual sites in the larynx and pharynx was determined by pathologic study of neck dissection specimens from 253 patients without palpable lymph nodes (NO neck). The incidence of occult lymphatic metastases in the NO neck and the need for elective neck irradiation were least for cancers of the transglottis and central supraglottis (14-16%), intermediate for cancers of the glossoepiglottis and the marginal supraglottis (20-38%), and greatest for cancers of the pyriform sinus (47%). The risk of nodal recurrence increased from 8% for those without cancer in lymph nodes to 38% for those with occult or palpable cancer in lymph nodes. A policy of observing the NO neck in patients with a low incidence of occult lymphatic metastases and a low risk of neck recurrence to avoid the unnecessary irradiation of many to benefit a few is discussed.

The relationship of complication rate to external and intracavitary dose in one thousand patients with carcinoma of the cervix stages IB-IVA

Between 1959 and 1976, approximately one thousand patients with stages 1B through IVA invasive carcinoma of the cervix were treated at the Malliric,krodt Institute of Radiology. Most of the patients were treated with a combination of external photon beam therapy and intracavitary implants. Part of the external treatment uses a blocking system in the midline to protect the area receiving a high dose from the implant. Before 1963, this blocking system was defective and resulted in a high dose of irradiation to the bladder and rectum. After 1963, this problem was corrected and the bladder and rectum were properly blocked when the external irradiation was directed mainly to the parametrial areas. For those patients treated with external radiation using the defective blocking system before 1963, the external dose to the bladder and rectum was calculated by adding the total external dose; that is, both whole pelvis and paras metrial external radiation. For those patients treated after 1963, when the bladder and rectum were properly blocked at the time of parametrial irradiation, the external dose to the bladder and rectum was taken as the whole pelvis dose, omitting any external dose to the parametrium. These external doses to the bladder and rectum were then added together with the intracavitary doses calculated at arbitrary points defined on the bladder and rectum, respectively, using the implant films and computerized isodose curves. (The dose rate for intracavitary irradiation is, of course, different from that for external irradiation. However, as a first approximation, we have simply added them together). The severe gastrointestinal and genito-urinary complication rates are plotted against the dose to the rectum and bladder, respectively. A clear-cut correlation between the complication rates and the dose of irradiation is demonstrated. These complications will also be correlated separately with the total dose delivered to the lateral parametrium.