Gerald E. Hanks

Elective pelvic irradiation in stage A2, B carcinoma of the prostate: analysis of RTOG 77-06☆

From 1978 to 1983 the Radiation Therapy Oncology Group conducted a study to evaluate the role of elective pelvic lymph node irradiation in carcinoma of the prostate. Eligible patients were those with clinical Stage A2 (occult disease with more than 3 positive chips and poorly differentiated tumor) and Stage B without clinical (lymphangiogram) or biopsy evidence of lymph node involvement. The patients were randomized to receive 6.5 weeks of either prostatic bed irradiation only 6500 cGy at 180-200 cGy per treatment or pelvic node irradiation to 4500 cGy with a boost of 2000 cGy to the prostatic bed bringing the total dose to 6500 cGy. As of February, 1988, the median follow up has been 7 years and there were 445 analyzable cases who were evaluated for local control, incidence of distant metastases, ned (no evidence of disease) survival and survival. The results of the study revealed no statistically significant benefit of elective pelvic irradiation.

Conformal static field therapy for low volume low grade prostate cancer with rigid immobilization

The ability to improve existing standards of treating prostate cancer was investigated. To deliver a homogenous dose to the prostate with as little normal tissue margin as practical, seven patients with low volume carcinoma of the prostate were immobilized with alpha cradle body casts prior to using a CT-based 3D treatment planning system and beams eye view (BEV) template. All patients had clinical Stage B-1 prostate cancer of favorable histologic differentiation (Gleason Score 2-5). A four field box technique was used, each beam having a single customized cerrobend block cut-out conforming to the exact contour of the prostate. To assess the accuracy of this process, daily port films were taken for 5 consecutive days and compared to a matched control group who were treated in a similar fashion, but were not casted. Dose volume histograms illustrate an average of 14% of bladder dose and 14% of rectal dose that can be eliminated using this technique when compared to field sizes and block placement in our previous technique. Daily setup variation was markedly improved using the cast, with a median daily variation of 1 mm as compared to 3 mm without the cast. The average range of movement for each of the seven casted patients was 3.3 mm as compared to 8 mm for the seven uncasted patients. Immobilization eliminated the worst 10% of all daily positioning errors. Using CT treatment planning with the patient casted and BEV allows for precise block placement with the prostate gland in its proper orientation during daily treatment. With improved immobilization and precise localization of the prostate gland, margins around the target can be made significantly smaller, and this may translate into a decrease in acute and/or late complications.

Impact of improved irradiation technique, age, and lymph node sampling on the severe complication rate of surgically staged endometrial cancer patients: a multivariate analysis.

PURPOSEnLimited information is available regarding factors that predispose to complications following postoperative pelvic radiotherapy (RT) for endometrial cancer. To address this issue, patients with clinically staged I/II endometrial cancer who received postoperative RT following total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH/BSO) with or without lymph node sampling (LNS) were studied.nnnPATIENTS AND METHODSnFrom 1960 through 1990, 235 patients with adenocarcinoma of the endometrium received postoperative RT after surgical staging. Multiple factors were evaluated to determine associations with severe complications. Pretreatment factors included age, stage, comorbidities. Treatment-related factors consisted of LNS, total RT dose, volume of RT fields, dose per fraction, total number of RT fields, number of RT fields treated per day, machine energy, and addition of vaginal implant.nnnRESULTSnThe 5-year actuarial risk of a severe complication was 5.5%. Factors associated with an increased risk of complications in univariate analysis included age more than 65 years (11% v 2%), use of only one portal per day (40% v 3%), use of anteroposterior/posteroanterior fields (23% v 4%), total dose > or = 50 Gy (8% v 2%), and LNS (11% v 3%). In a multivariate analysis, only older age, LNS, and the use of one field per day were significant. Increased risks associated with a total dose > or 50 Gy and the anteroposterior/posteroanterior technique were entirely attributable to the use of one field per day. A subanalysis among patients who had adequate RT techniques (eg, multiple fields treated per day) showed a significant increase in complications (7% v 1%) for those with and without LNS, respectively.nnnCONCLUSIONSnSevere complications associated with adjuvant RT for endometrial cancer were increased among patients who were older or underwent LNS or received suboptimal RT technique. Pelvic RT using proper methods can be delivered with acceptable risks.

Influence of age, prior abdominal surgery, fraction size, and dose on complications after radiation therapy for squamous cell cancer of the uterine cervix. A patterns of care study

The 1973 and 1978 national surveys conducted by the Patterns of Care Study (PCS) for squamous cell cancer of the uterine cervix were combined to analyze factors associated with complications after radiation therapy (RT). Overall, 1558 patients were reviewed, with a median follow‐up of 43 months. Major complications (defined as necessitating hospitalization for management) were seen in 152 of 1558 (9.8%) patients, with a 5‐year actuarial rate of 14%. A number of pretreatment and treatment factors were analyzed with respect to complications. In univariate analysis, significant pretreatment and treatment factors associated with an increase in complications included young age, prior laparotomy for staging, history of prior abdominal surgery, increasing stage, use of external RT, high fraction size, cesium source, and high para‐central (PCS point A) and lateral (PCS point P) doses. Multivariate analysis showed a history of prior abdominal surgery, paracentral dose greater than 7500 cGy, use of cesium, daily fraction size greater than 200 cGy, and age younger than 40 years to be associated independently with complications. A detailed analysis of the type of and time to complications is presented. The knowledge and skillful management of these pretreatment and treatment factors may improve the therapeutic ratio for RT, which is the most active curative modality against cervical cancer.

Prognostic factors in carcinoma of the prostate— analysis of rtog study 75-06

A total of 566 evaluable patients were accessioned to a phase III RTOG study of extended field irradiation in carcinoma of the prostate from 1976 to 1983. Eligible patients were those with locally advanced disease, either clinical Stage C or clinical Stage A2 or B with pelvic lymph node involvement. The treatment consisted of irradiation of the regional lymphatics followed by a boost to the prostate. The data have been analyzed extensively to identify variables of potential prognostic significance. The assessed factors include tumor size, clinical stage, the degree of histological differentiation, nodal status, serum acid phosphatase status, hormonal management status, age, and race. These factors have been assessed as to their interdependence and correlation with the clinical course (study endpoints) using univariate analyses and Coxs Regression model. Significant interdependence of tumor size and Gleason score and tumor size and acid phosphatase was identified. The population receiving hormonal management either prior to or during radiotherapy had a significantly higher proportion of high grade tumors. Correlation of the assessed variables and the study endpoints (local control, incidence of distant metastases, NED survival, survival) singled out the degree of histological differentiation as the most powerful prognostic factor for all the endpoints. Age proved a useful predictor of local control (younger patients failed at a significantly higher rate), as did tumor size. Elevation of serum acid phosphatase correlated well with the incidence of metastatic disease but was not a useful predictor of survival. Tumor size and hormonal management status correlated well with the incidence of metastatic disease but only when analyzed separately from other factors. Their prognostic value was absent when Cox regression analysis was applied. Nodal status did not correlate well with any of the study endpoints, indicating then that in patients with clinical Stage C disease, treated with definitive radiotherapy to the prostate and regional lymphatics, this parameter may have limited prognostic usefulness. Although patients who received concomitant hormonal management had a significantly higher proportion of high grade lesions, their clinical course fared favorably in comparison with the population not receiving concomitant hormonal management. This may indicate a beneficial effect of adjuvant hormonal treatment which needs to be tested in a prospective study.

Correlation of radiotherapeutic parameters and treatment related morbidity in carcinoma of the prostate--analysis of RTOG study 75-06.

Treatment related morbidity, recorded in patients entered onto a RTOG phase III study (testing the value of periaortic irradiation in locally advanced carcinoma of the prostate), has been correlated with radiotherapeutic parameters to identify and quantify the relationship with treatment volumes, doses, and techniques. Between 1976 and 1983 a total of 526 analyzable cases were entered onto the study. The study design entailed randomization to either pelvic irradiation followed by a prostate boost or pelvic and periaortic irradiation followed by a prostate boost. Periaortic irradiation was not associated with a significantly increased incidence of bowel injuries manifested by diarrhea. No correlation between the total dose to the regional lymphatics (ranging from 4400 to 5100 cGy) and the incidence of bowel and bladder injuries could be established. Doses to the prostate in excess of 7000 cGy have not resulted in a significantly increased incidence of bladder injuries, but have been associated with a significant increase in the incidence of bowel injuries manifested by diarrhea. The techniques of pelvic irradiation did not seem to significantly influence the incidence of bowel or bladder complications. The technique of delivery of the prostatic boost did seem to influence the incidence of bowel injuries. This refers to the lateral boost technique and the perineal boost technique which have been associated with a higher incidence of diarrhea. All of the conclusions based on this analysis are applicable only to treatment volumes and dose ranges used in this study and to conventional fractionation of 180 to 200 cGy per day.

Complications from large field intermediate dose infradiaphragmatic radiation: An analysis of the patterns of care outcome studies for Hodgkin's disease and seminoma☆

There are only infrequent complications from intermediate dose infradiaphragmatic radiation to the para-aortics or para-aortic and iliac nodal regions as given in Hodgkins disease or seminoma. Nonetheless, such complications can cause significant debility and may be lifelong. Treatment related factors associated with such complications should be identified and where possible, avoided. We have analyzed the records of 1,026 patients treated nationwide in the Patterns of Care Outcome. Studies including the Hodgkins national practice survey (387 patients), Hodgkins large facility survey (253 patients), and Seminoma national practice survey (386 patients). There were 883 patients who received infradiaphragmatic radiation to the para-aortics or para-aortic and iliac regions. Complications which occurred in these patients included gastrointestinal injury, hepatitis, nephritis, gonadal injury, hematopoietic injury, second malignancy, and miscellaneous others. There were 139 complications of any severity and 35 major complications requiring hospitalization for management. The 3-year actuarial complication rates were 14% and 4% for any and major complications, respectively. There was a statistically significant increase in both any complications and major complications with dose (p less than .01). The most frequent complications were those related to gastrointestinal injury such as peptic ulceration, hemorrhage, chronic diarrhea, and intestinal obstruction. Major bowel complications comprised 60% (21/35) of major complications and increased with dose from 1% for doses less than 3,500 cGy to 3% for doses greater than or equal to 3,500 cGy (p = .03). This study indicates that total dose is an important factor in determining complications, particularly gastrointestinal injury, in patients receiving infradiaphragmatic radiation in Hodgkins disease and seminoma and that prior G.I. disease is associated with an increased risk of radiation related bowel complication. The radiotherapist should seek to optimize the therapeutic ratio in these diseases where gross disease can be controlled with 3500 cGy or less with few exceptions.

Prognostic factors in patients with bladder carcinoma treated with definitive irradiation

An analysis was performed of 116 patients with bladder carcinoma who completed definitive radiotherapy at a single institution. Patients were analyzed for survival and local control. The overall 5‐year survival rate was 34%. A multivariate analysis of survival showed disease stage, hemoglobin level, histologic grade, and total dose to be significant factors in outcome. The local control rates for Stage A, B, C, and D patients were 26%, 36%, 18%, and 0%, respectively. The multivariate analysis revealed disease stage and pretreatment hemoglobin level to be significant predictors of local control. In patients unsuitable for surgery or current combined technique protocols, high‐dose irradiation may offer some patients survival and local control. Furthermore, prognostic factors in this study may aid in the stratification necessary for current protocol designs.

The effect of overall treatment time on the outcome of definitive radiotherapy for localized prostate carcinoma: The radiation therapy oncology group 75-06 and 77-06 experience

From 1976 to 1983, 1091 patients were entered into RTOG protocols 75-06 and 77-06. Of these, 780 patients complied with protocol requirements, received a minimum tumor dose of greater than or equal to 6500 cGy, and received no endocrine therapy. There were 78, 342, and 360 patients with localized prostate carcinoma, Stages T1b(A2), T2(B), and T3,4(C), respectively. The potential follow-up period ranges from 6 years 5 months to 13 years 3 months, with a median follow-up of 9 years. This study examines the influence of overall treatment time on the outcome of definitive radiotherapy for localized prostate carcinoma in this patient population. Within each stage, patients were divided into three groups according to the total number of elapsed days while on treatment: within 49 days (less than or equal to 7 weeks); 50 to 63 days (8 to 9 weeks); and greater than or equal to 64 days (greater than 9 weeks). Based on actuarial analysis, within each stage, the overall treatment time did not have any impact on the following: overall survival, NED survival, or local/regional control. When grouped under different histologic grades, that is, Gleason scores 2-5, 6-7, and 8-10, the actuarial local/regional control showed no statistical difference among the three groups. The actual local/regional failures were analyzed and stratified by stage and Gleason scores, and no statistical difference was noted among the three groups for each stratification. The range of local/regional failure rates among the three groups for T1b(A2), T2(B), and T3,4(C) disease were 0%-8%, 16%-23%, and 24%-27%, respectively. The corresponding range of local/regional failure rates for patients with Gleason scores of 2-5, 6-7, and 8-10 were 13%-14%, 18%-22%, and 22%-33%, respectively. The incidence of late complications was not related to the number of elapsed treatment days. Therefore, the overall treatment time does not have an impact on the outcome of definitive radiotherapy for localized prostate carcinoma. It is hypothesized that prostate carcinoma behaves as late-reacting tissue in which there is little, if any, accelerated repopulation of clonogenic tumor cells during the later half of a protracted course of radiotherapy. This observation is in direct contrast to that suggested for head and neck carcinoma and bears important implications in daily radiotherapeutic management of patients with prostate carcinoma.

Palliative radiotherapy for symptomatic adrenal metastases

To evaluate the role of palliative radiotherapy for adrenal metastases, a retrospective review was performed on 16 patients treated between 1972 and 1988 for palliation of symptomatic adrenal metastases. The median patient age was 56 years. In 15 cases lung cancer was the primary site (7 adenocarcinomas, 3 squamous cell carcinomas, 3 large cell carcinomas, and 2 small cell carcinomas) and in 1 case there was an unknown primary (squamous cell carcinoma). Ten of 16 patients were treated with 3000 cGy to opposed anterior and posterior fields (300‐cGy fractions [four patients] and 250‐cGy fractions [six patients]). The remaining six patients were treated with a variety of techniques, with total doses ranging from 2925 cGy to 4500 cGy. The patients were analyzed for response at their first follow‐up visit (2 to 4 weeks after treatment). The overall response rate was 75% (12 of 16 patients). Six patients (38%) had complete pain relief without medication that lasted until death. Two patients had marked pain relief, but still required analgesics. Four patients had marked or moderate pain relief that did not continue through follow‐up. Four patients had minimal to no response. All patients were observed until death, with a median survival time after irradiation of 3 months (range, 0.5 to 11 months). Although the prognosis for patients with adrenal metastases is poor, radiotherapy to symptomatic adrenal metastases can be administered with a high probability of achieving effective palliation.