John M. Bedwinek

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.

Prognostic indicators in patients with isolated local–regional recurrence of breast cancer

A retrospective review was undertaken of 129 patients with isolated local‐regional recurrence of breast cancer following radical or modified radical mastectomy. The overall survival and disease‐free survival for these patients five years from the time of local‐regional recurrence was 36 and 13%, respectively. The clinical stage at initial diagnosis, the number of histologically positive nodes at mastectomy, menopauseal status, and the location of the recurrence (chest wall vs. nodal) were all found to have no significant effect on survival or disease‐free survival. On the other hand, the number of recurrences, the size of the largest recurrence, and the time interval between mastectomy and recurrence (disease‐free interval) had definite prognostic significance. A single recurrence, the size of the largest recurrence being ≥ 1 cm, and a disease‐free interval of longer than 24 months predicted a good prognosis; on the other hand, multiple recurrences, the size of the largest recurrence being <1 cm, and a disease‐free interval of less than 24 months predicted a bad prognosis. Eighty‐one percent of the patients ultimately developed distant metastases; the incidence of distant metastases was the same for patients with factors predicting a good prognosis as it was for those with factors predicting a bad prognosis. The time to appearance of distant metastases, however, was significantly longer in the former group of patients than in the latter. The information from this analysis should be useful in designing future clinical trials involving patients with isolated local‐regional recurrence of breast cancer.

Analysis of failures after definitive irradiation for epidermoid carcinoma of the nasopharynx.

From 1955 to 1976, 111 patients were treated with definitive radiotherapy for epidermoid carcinoma of the nasopharynx. There was a definite correlation between recurrence at the primary site and T‐stage; 9.5% of T1–2 patients, 38.1% of T3 patients and 54.1% of T4 patients had local recurrences. Similarly, failure in the neck correlated with N‐stage, being negligible for N0 and N1 but 28.6% for N2 and 36.1% for N3. The incidence of distant metastases had no correlation with T‐stage but correlated very closely with N‐stage.

Analysis of failures following local treatment of isolated local-regional recurrence of breast cancer

Abstract Obe hundred fifty-seven patients with local-regional recurrence of breast cancer but without co-existing distant metastases were reviewed. The incidence of failure to control the local-regional recurrence was essentially the same whether the recurrence was treated with radiotherapy alone (62% ), surgery alone (76% ), or with a combination of the two (60 % ). A detailed analysis of the failures occurring in the patients treated with radiotherapy, with or without surgery, showed that most of the failures were because of a) inadequate doses of irradiation, b) the use of fields that were too small, and c) the lack of elective irradiation to the chest wall and supraclavicular fossa. Of the 100 patients with uncontrolled local-regional disease, 62% developed clinical symptoms that markedly impaired the quality of life. All of these symptoms were directly caused by the uncontrolled local-regional disease. Specific recommendations for the treatment of isolated local-regional recurrence are made.

Dose-response analysis for nasopharyngeal carcinoma: an historical perspective.

Historical review of 118 patients with nasopharyngeal cancer treated in our institution from 1950–1978 showed a 20% improvement in tumor control for patients irradiated during the most recent period (1974–1978). This improvement was attributed to prescription of higher doses of radiation as well as improvements in technical accuracy and dose delivery to the tumor during that period. Rates of severe and mild complications were comparable and survival was not significantly altered over time despite improved tumor control. Within the range of doses delivered, there was no improvement in tumor control with increasing doses of radiation for small or large nasopharyngeal carcinomas. The dose—response analysis for tumor control was less than ideal because a number of prerequisites were lacking and because the study extended over a 28‐year span during which there were significant changes in technology and physician orientation.

Gestational carcinoma of the female breast

Few neoplastic diseases can equal the amazing complexity and sheer perversity of carcinoma of the breast. No doubt as many decades of research lie ahead in its study as already have passed. Clinicians have long appreciated the special relationship of the disease to gestation. Diagnosis and treatment of breast cancer during pregnancy represent only a small part of this fascinating relationship. Although indispensable as research tools, animal models pertain to the human disease only in limited, ill-defined ways. The etiology of human breast cancer remains unclear; chemical, viral, hormonal, genetic, and immunologic theories have all been put forward as possibilities. Although gestation clearly alters both the initiation and growth of mammary tumors, its exact role in the various theoretical considerations remains a mystery. The obstetrician-gynecologist holds an important front-line position in the war against breast cancer, as does any provider of primary care to women, and, indeed, as do women themselves. Rather than decrease vigilance during pregnancy, the physician should pursue with extra vigor any breast mass discovered in the gravid patient, when the clinical examination is even less reliable than usual. The finding of a breast mass usually necessitates biopsy. Except for the inclusion of specific pregnancy-related problems, such as galactocele, the diagnostic spectrum of breast masses removed during pregnancy does not differ from that in nonpregnant women. The discovery of a highly suspicious breast mass, or the confirmed biopsy diagnosis of malignancy, in a pregnant patient should indicate the need for referral to a surgical oncologist versed in this unusual problem. The best approach to gestational breast cancer continues to be the team approach, with consultation from specialists in obstetrics, surgical oncology, anesthesiology, nuclear medicine, radiology, radiation oncology, pathology, and medical oncology. The age and general condition of the patient, the extent of the tumor, the stage of gestation, and the informed opinions of the patient and her spouse help to determine the therapeutic strategy. Careful staging not only guides present therapy but also the therapy of future victims through continued investigation. Most surgeons favor operation without delay if cure seems within reach. Mastectomy, with or without cesarean section, can be accomplished without detriment in the hands of a knowledgeable surgeon-anesthesiologist team. By following certain guidelines, the search for metastasis can be conducted safely and appropriately. The clinical situation occasionally may require the initiation of adjuvant radiotherapy or chemotherapy during pregnancy, by experienced consultants. Ongoing studies of tissue hormone receptors and cell kinetics will continue to give insight into the effects of gestational hormones on breast cancer and can aid in the selection of treatment options for the individual patient...

Stage III and localized stage IV breast cancer: Irradiation alone vs irradiation plus surgery

One hundred forty-seven patients with non-inflammatory, Stage III and IV cancer were treated with irradiation alone (54 patients) or with a combination of irradiation and mastectomy (93 patients). In the T3 category, the local failure rate was 45% (5/11) for the irradiation alone patients vs 12% (3/25 for the irradiation plus surgery patients; in the T4 category these figures were 65% (28/43) vs 13% (9/68), respectively. Corresponding local failure rates by size of primary tumor were 50% (2/4) vs 15% (5/29 for tumors 0-5 cm, 43% (9/21) vs 14% (6/45) for 5-8 cm tumors, and 75% (22/29) vs 5% (1/20 for tumors greater than or equal to 8 cm. The rates of regional failure for the two treatment methods were compared according to N stage; they were 9% (2/23) for irradiation alone vs 11% (8/76) for irradiation plus surgery in the N0-1 category, and 58% (18/31) vs 18% (3/17), respectively, for the N2-3 category. A dose response analysis for patients with tumors greater than 5 cm treated with irradiation alone did not show a decrease in local failure rate with increasing total tumor dose over a range of 4000 to 7000 rad, suggesting that doses in this range are too low for these large tumors. Since a significant late complication rate has been reported with doses higher than this, patients with non-inflammatory, but large (greater than 5 cm) tumors, should be treated with a combination of surgery and irradiation whenever possible to achieve maximum local-regional control with a minimum probability of complications. In 36 patients with inflammatory carcinoma, the rates of local and regional failure were 52% (15/29) and 38% (11/29), respectively, for patients treated with irradiation alone, and 14% (1/7) and 29% (2/7), respectively, for patients receiving irradiation plus surgery. Since none of these differences were statistically significant, one cannot conclude that surgery should necessarily play a role in the treatment of inflammatory carcinoma.

Failure patterns in gynecologic cancer

In reviewing the literature on the patterns of failure in gynecologic malignancies, it is essential to define the type of recurrence resulting from the treatment program pursued. Categorizing them into local recurrences, marginal recurrences, parametrial recurrences, periaortic lymph node recurrences, abdominal recurrences, and distant metastatic disease become an important part in the design of new treatment programs in management. Most recurrences are actually the result of persistent disease. Therefore, the full extent of disease at the time of initial presentation should be determined. Pre-treatment surgical exploration obviously defines more precisely the tumor extent than does clinical stage alone. Samples of retroperitoneal abdominal lymph nodes in cervical, endometrial and ovarian cancer have shown more frequent involvement than previously suspected.

Treatment of stage I and II adenocarcinoma of the breast by tumor excision and irradiation

Abstract In recent years there has been an increase in the number of women with breast cancer seeking an alternative to mastectomy. When seeing these patients in consultation, radiation oncologists should make an effort to enter them into one of the two current United States clinical trials involving breast-conserving surgery and irradiation. If a patient cannot or will not be entered into one of these trials, then her management should be based on careful consideration of the various factors involved in the selection of patients for breast-conserving surgery and irradiation, particularly tumor size, breast size and patient attitude. In addition to a discussion of these selection factors, this communication includes a description of the different types of breast-conserving surgery and the technical details involved in irradiating the intact breast.