Silvio A. Aristizabal

The relationship of time-dose fractionation factors to complications in the treatment of pituitary tumors by irradiation☆

Abstract The records of the Radiotherapy Division of the Radiology Department of Vanderbilt University Hospital were reviewed for the years 1952-71. During that period of time, 122 patients with diagnosis of pituitary adenomas were treated by external irradiation. A variety of techniques (2 or 3 stationary fields, 180° rotational fields), equipment ( 60 Co, 6 MeV Linac) and fractionation schedules (treating 4, 5 or 6 days per week, doses ranging between 150 and 280 rad per fraction), were used. Five patients developed severe complications: 1 with brain necrosis and 4 with blindness related radiation damage to optic pathways. From analysis of time-dose factors (TDF), it is evident that the risk of complications increases from 0% to 25% as the dose exceeds a TDF of 80. Although a significant increase in success rate has resulted from doses in excess of 3500 rad, there is little support for believing that doses in excess of 5000 rad (TDF 80) achieve improved results.

Second-look laparotomy in epithelial ovarian carcinoma. Prognostic factors associated with survival duration

This article that reports on 70 consecutive patients is one of only a few studies of advanced ovarian cancer that have attempted to define predictive factors associated with survival duration after second‐look laparotomy. As in many other investigations, several factors have been analyzed for predicting second‐look outcome. The prognostic variables analyzed in this study included age, stage, histologic grade, residual disease status after initial surgery, and type (cisplatin versus no cisplatin) and number of cycles of chemotherapy. Only stage (P = 0.002) and optimal disease (less than 2 cm residual tumor size) after initial surgery (P < 0.001) were significantly associated with the absence of disease at second‐look laparotomy, and both were significant predictors of second‐look outcome in a multivariate logistic regression model. Their impact on actuarial survival after second‐look laparotomy diminished, however. Actuarial survival after second‐look laparotomy was associated with residual tumor size at second‐look surgery (P = 0.02). According to second‐look findings, the 3‐year actuarial survival rates and standard errors were as follows: no pathologic evidence of disease, 80.7% ± 13.4% 3‐year survival; microscopic disease plus less than or equal to 2 cm residual disease, 49.1% ± 13.1% survival; and gross residual disease (i.e., greater than 2 cm maximum tumor diameter), 29.5% ± 11.4% survival. We also examined the effect of extensive tumor resection at second‐look laparotomy on survival for patients with greater than 2 cm gross residual disease. Optimum resection (less than 2 cm residual tumor mass) resulted in significantly greater survival than suboptimum resection (P < 0.001). This strongly suggests that there is a survival advantage associated with optimum resection at second‐look laparotomy.

Prognostic variables in the treatment of squamous cell carcinoma of the vulva

Abstract Records of 98 patients undergoing surgery for squamous cell carcinoma of the vulva between 1960 and 1982 were analyzed to evaluate and develop treatment policy. There were 32, 34, 26, and 6 patients in FIGO stages I–IV, respectively. Eighty-six patients underwent radical vulvectomy, 8 patients underwent less extensive procedures, and 4 underwent more extensive procedures. Eighty-seven patients underwent inguinal node dissection, and 40 underwent pelvic node dissection as well. Eight patients received external beam irradiation. Actuarial 5-year survival was 57%. Age, tumor size, FIGO (clinical) stage, surgically determined T and N stages, tumor differentiation, lymph vessel invasion, extent of surgical procedure, and adjuvant irradiation were analyzed to determine their effects on local control, freedom from distant metastases, and survival, using single variable and multivariate analysis. Local control was significantly related to FIGO stage; freedom from distant metastasis was significantly related to surgical N stage, tumor size, and surgical T stage; survival was significantly related to surgical N stage, tumor size, surgical T stage, age, and lymph vessel invasion. Metastatic involvement of inguinal lymph nodes was significantly correlated with tumor size and differentiation. Of 87 evaluable patients, 33 had inguinal node involvement, and of these, 17 developed recurrent disease. All 7 patients with pelvic node metastases had positive inguinal nodes, and all died; the cause of death could be determined in 5, of whom 4 manifested distant metastases. Pelvic lymphadenectomy conferred no survival benefit in this series, even in the presence of positive inguinal nodes. Local vulvar recurrence is a significant problem in patients with positive inguinal nodes, and postoperative irradiation should be directed to this area in these patients. Patients with vulvar recurrences, esepcially those occurring at least 2 years after surgery, can be successfully salvaged, and should therefore be treated aggressively.

Bilateral primary germ cell testicular tumors: report of four cases and review of the literature.

Bilateral primary germ cell tumors of the testicle are rare. The last comprehensive review of the literature (1955) revealed a 1.6% incidence. However, during the past twenty years, cases have been reported more often, raising the questions of increased frequency due to prolonged survival following surgery and/or roentgen therapy for unilateral tumors. A search of the medical journals during the past two decades fails to show any increased frequency of bilaterality (1.56%). All general combinations of cell types may occur and the tumors may appear simultaneously or sequentially. Successive seminomas are seen more often followed in frequency by concurrent seminomas. Although 50% of the second primaries were diagnosed within five years, 3% of the patients developed the second tumor after 20 years, stressing the need for extended follow‐up. Factors affecting the diagnosis, management and prognosis of bilateral testicular tumors are discussed. Four additional cases of bilateral germ cell tumors are described.

External beam radiotherapy in cancer of the prostate: The university of arizona experience

Between 1973 and 1979, 218 patients with adenocarcinoma of the prostate stage A2 through D1 were treated with primary external beam radiotherapy. The majority of the patients (211) received 6000-7000 rad to the prostate using a small (160) or large (58) volume technique. With a minimum follow-up of 36 months and a maximum of 120 months, the control rates of the local tumor were 96%, 95%, 88% and 81% for stage A2, B, C and D1. The corresponding 5-year survivals were 100%, 82%, 60% and 42%. Mild to severe complications were documented in 35 cases (16%). The frequency and severity of the complications correlated with the size of the irradiated volume and history of previous surgery. The use of large fields, to encompass the regional lymphatics, is not associated with improved survival.

Complications of irradiation related to apparent drug potentiation by adriamycin

Abstract Clinical observations were made on 18 patients who were treated with combined irradiation and chemotherapy. A total of 21 irradiation reactions were noted, remarkable for their severity and persistence. Adriamycin (ADM) was the one drug common to all chemotherapeutic regimens. The reactions involved skin, esophagus, heart, lung and oral mucosa. No consistent pattern was established between the type or severity of reaction and the dose of drug or irradiation, nor of the temporal relationship of one to the other. It appears that ADM toxicity may potentiate irradiation reactions and that a “standard” total dose may be equivalent to a dose of irradiation on the order of 1000 rad. Since ADM persists in body tissues for prolonged periods of time, irradiation reactions may occur unexpectedly. All reactions improved, but eventual long-term effects cannot be determined at this time. A plea is made for controlled observations to determine safe schedules for the combination of these agents.

RELATIONSHIP OF TIME DOSE FACTORS TO TUMOR CONTROL AND COMPLICATIONS IN THE TREATMENT OF CUSHING'S DISEASE BY IRRADIATION?

Abstract The records of the Radiotherapy Division of the Radiology Department of Vanderbilt University Hospital were reviewed for the period 1952–1970. During those 19 years 45 patients with a well-documented diagnosis of Cushings disease were treated initially by external irradiation of the pituitary. All of the patients were treated with megavoltage equipment using photons. When the results of irradiation are compared against total doses of radiation, it is evident that the control rate is unsatisfactory at doses less than 4000 rad and the maximum benefits of irradiation are evident in the 4500–5000 rad dose range. It is also clear that the complication rate increases as the dose exceeds 4800 rad. If the various treatment regimens of irradiation are converted to “equivalent” doses by the Nominal Standard Dose (NSD) or Time-Dose-Fractionation (TDF) methods, the relationship between “dose” and efficacy of therapy and complications is demonstrated. In order to reduce the possibility of treatment-related morbidity, the use of three or more small (4 × 4 cm) treatment portals or rotational techniques is recommended to a pituitary dose of 4600–5000 rad treating 5 days a week for 5–6 weeks.

Adriamycin--irradiation cutaneous complications

Four cases of abnormally severe skin reactions including an instance of skin necrosis occurred in patients with breast cancer who were treated with cyclophosphamide, adriamycin and irradiation concurrently following mastectomy. These unusual skin reactions apparently resulted from the interaction of radiation with adriamycin and prompted us to modify both the radiation dose and the timing of administration of chemotherapy. To date, no unusual or severe skin reactions have been observed in 14 patients who have received chemotherapy with adriamycin plus radiation in accord with this modified treatment plan.

A phase II trial of mitomycin, vincristine, bleomycin, and cisplatin (MOBP) as neoadjuvant therapy in high-risk cervical carcinoma

Twenty patients with locally advanced or metastatic cervical carcinoma were treated with mitomycin, vincristine, bleomycin, and cisplatin (MOBP), prior to radiotherapy (RT) of curative intent. Five patients had stage I disease, 2 stage II, 10 stage III, and 3 stage IV. All but one patient with stage I and II disease had nodal metastases. Patients received two courses of MOBP prior to and cisplatin q 3 weeks during RT. Response rates after completion of MOBP and prior to RT were as follows: 3/18 (16.6%) patients had a complete response (CR), 10/18 (55.5%) had a partial response (PR), 3/18 (16.6%) had improvement, and 2/18 (11.1%) had no response (NR). Five patients developed radiation complications. Of 7 patients with stage I and II disease, 6 (86%) currently have no evidence of disease (NED) (median 27 months). Of 13 patients with advanced disease, 3 (23%) are NED (median 17 months), 8 (61.5%) have expired, and 2 (15.4%) are alive with disease. MOBP is associated with significant response rates in the untreated patient but has not improved survival in patients with advanced disease. Patients with early disease and positive nodes may benefit from this regimen.

Treatment of advanced cancer of the cervix with transperineal interstitial irradiation

A pilot study using transperineal interstitial implantation to the parametrium in patients with locally advanced carcinoma of the cervix or with distorted anatomy is presented. Twenty-one consecutive patients (2 cervical stump Stage IB, 3 Stage IIB, 15 Stage IIIB, 1 Stage IVA) received one (12) or two (9) implants following 40-45 Gy whole pelvis external irradiation. In addition 8 patients underwent staging laparotomies concurrently with the first implant procedure. Control of the pelvic tumor was accomplished in 18 of 21 patients (85%) with a mean follow-up of 26 months (range 15 to 48 months). Seven patients (33%) developed long term complications (fistula 3, superficial necrosis of the vagina 1, severe proctitis or cystitis 3). Six of the complications occurred in 8 patients (75%) who had radioactive sources placed on the surface of the vaginal obturator as a substitute for the lack of tandem. In contrast, only 1 in the remaining 13 patients (8%) who did not have obturator sources placed, developed long term complications.