Four-year Prostate-specific Antigen Response Rate as a Predictive Measure in Intermediate-risk Prostate Cancer Treated With Ablative Therapies: The SPRAT Analysis.

AIMS: There is a lack of early predictive measures of outcome for patients with intermediate-risk prostate cancer (PCa) treated with stereotactic body radiotherapy (SBRT). The aim of the present study was to explore 4-year prostate-specific antigen response rate (4yPSARR) as an early predictive measure. MATERIALS AND METHODS: Individual patient data from six institutions for patients with intermediate-risk PCa treated with SBRT between 2006 and 2016 with a 4-year (42-54 months) PSA available were analysed. Cumulative incidences of biochemical failure and metastasis were calculated using Nelson-Aalen estimates and overall survival was calculated using the Kaplan-Meier method. Biochemical failure-free survival was analysed according to 4yPSARR, with groups dichotomised based on PSA <0.4 ng/ml or ≥0.4 ng/ml and compared using the Log-rank test. A multivariable competing risk analysis was carried out to predict for biochemical failure and the development of metastases. RESULTS: Six hundred and thirty-seven patients were included, including 424 (67%) with favourable and 213 (33%) with unfavourable intermediate-risk disease. The median follow-up was 6.2 years (interquartile range 4.9-7.9). The cumulative incidence of biochemical failure and metastasis was 7 and 0.6%, respectively; overall survival at 6 years was 97%. The cumulative incidence of biochemical failure at 6 years if 4yPSARR <0.4 ng/ml was 1.7% compared with 27% if 4yPSARR ≥0.4 ng/ml (P < 0.0001). On multivariable competing risk analysis, 4yPSARR was a statistically significant predictor of biochemical failure-free survival (subdistribution hazard ratio 15.3, 95% confidence interval 7.5-31.3, P < 0.001) and metastasis-free survival (subdistribution hazard ratio 31.2, 95% confidence interval 3.1-311.6, P = 0.003). CONCLUSION: 4yPSARR is an encouraging early predictor of outcome in patients with intermediate-risk PCa treated with SBRT. Validation in prospective trials is warranted.

Superior sulcus tumors: combined modality.

Twenty-four patients with superior sulcus tumors were seen between 1955 and 1989. Fifteen of these patients received combined-modality therapy. In 2 patients, this consisted of primary operation followed by postoperative radiotherapy, and, in 13, high-dose conventionally fractionated preoperative radiotherapy (5,500 to 6,475 cGy) followed by en bloc resection. Of the 13 patients who received radiotherapy preoperatively, 7 survived free of disease beyond 5 years and 2 others remained without evidence of disease after a shorter follow-up (greater than 2 years). The long-term survival in the combined-modality patients in this small series is superior to that reported for other patients receiving combined-modality therapy, and the morbidity appears to be within accepted limits despite the aggressive preoperative radiotherapy program. One postoperative death occurred in our only octogenarian, but there were no other acute complications. High-dose preoperative radiotherapy using current techniques and fractionation appears to be feasible in conjunction with contemporary surgical techniques. We believe this type of preoperative radiotherapy contributed to the apparent superior survival rate in this series and may also be applicable in the setting of other locally advanced (stage III) bronchogenic carcinomas.

Late effects following central nervous system radiation in a pediatric population.

Between 1970 and 1986, 120 children with central nervous system malignancy were treated with radiation therapy. These included 44 low-grade astrocytomas, 11 high grade astrocytomas, 32 medulloblastomas, 15 ependymomas/ependymoblastomas, 3 primitive neuroectodermal tumors and 8 pineal tumors. Seven children were treated without biopsy. Fifty-one treated children were evaluated for the effects of therapy on growth, endocrine function, IQ and hair regrowth. Mean height was 1.5 standard deviations below the mean height for the patient's age at study (range 0-5.7). Height was significantly less in patients receiving radiation to the pituitary and those with somatomedin-C deficiency. Height was also decreased with whole CNS radiation and spine dose > 20 Gy but not to a significant degree. Pituitary radiation in any dose increased the chance of endocrine deficiency (p = 0.004) and 21 of 51 patients had somatomedin-C deficiency. Mean IQ was 92.7 (+/- 18.8), with a slight trend toward decreased IQ with increasing whole brain dose of radiation. Hair regrowth was complete in 20 of 46 evaluated patients, diminished regrowth occurring with increasing volume and dose of radiation. No difference in the measured late effects could be detected with respect to age at treatment, sex, histology or location of tumor.

Analysis of preoperative intracavitary cesium application versus postoperative external beam radiation in stage I endometrial carcinoma.

Two groups of patients with surgical Stage I endometrial carcinoma treated at the LDS Hospital in Salt Lake City are analyzed. Group 1 comprises 112 patients treated from 1974 through 1976, during which time preoperative intracavitary cesium was routinely used in all patients. Group 2 comprises 117 patients treated 1981 through 1983 under the treatment policy of hysterectomy without preoperative cesium. High risk patients from each group (grade 3 and/or deep myometrial invasion) generally received similar postoperative external beam pelvic radiotherapy (4500-5000 cGy). While 5-year actuarial disease-free survival rates were similar in each group (94% Group 1 vs 91% Group 2), multivariate analysis by the Cox Regression Method revealed that inclusion within treatment Group 2 carried independent adverse prognostic significance (p = 0.018). Other independent predictors of adverse 5-year disease-free survival included deep myometrial invasion and increasing histologic grade. Group 1 patients with grade 3 lesions had a superior 5-year actuarial disease-free survival (76% vs 53%) compared to those from Group 2. Group 1 patients with deep myometrial invasion also had a superior 5-year disease-free survival (84% vs 69%). The remaining low risk patients (grade 1 or 2, less than 1/3 myometrial invasion) had an excellent 5-year disease-free survival with or without preoperative cesium. Immediate preoperative intracavitary cesium was well tolerated, did not obscure pathologic findings and in our experience, reduced the probability of recurrence in high risk Stage I endometrial carcinoma patients.

Radiotherapy for chordoma.

Twenty-five patients with gross residual chordoma after partial excision or biopsy were treated by radical radiotherapy at Royal Marsden Hospital between 1952 and 1981. The median duration of freedom from local progression following radiotherapy was 32 months. Twenty-four of the 25 patients (96%) had stabilization or reduction in symptoms. All 19 patients in whom pain was a major symptom had relief. The overall actuarial 5- and 10-year survival rates were 44% and 17%, respectively. The corresponding progression--free survival rates were 33% and 20%. Permanent cure was unusual with any radiotherapy dose, but doses higher than 55 Gy or a TDF of 90 were associated with a statistically significant improvement in duration of local control. Seven of 17 (41%) patients who received greater than 55 Gy had freedom from local progression for 5 or more years compared with only 1 of 8 patients receiving less than 50 Gy. Subtotal excision prior to radiotherapy did not appear to improve median survival or probability of long-term local control. Distant metastases were seen in 16% of the patients, derived entirely from sacrococcygeal lesions, but only half of these caused significant morbidity or death. Local control is obviously the overwhelming problem. High dose, generous volume radiotherapy is advocated.

Analysis of postoperative radiation therapy in stage I through III epithelial ovarian carcinoma.

A retrospective long-term analysis of the results of primary postoperative radiotherapy in 106 women with invasive epithelial ovarian carcinoma is presented. Forty-two women received open-field total abdominopelvic irradiation, and 64 received treatment by various subtotal abdominopelvic techniques. The mean follow-up of living patients in the two groups is 86 and 116 months, respectively. Women who had Federation International Gynecology and Oncology (FIGO) stages I through III-A with no postoperative residual disease, or less than 0.5-cm abdominal and/or less than 2-cm pelvic residual disease formed a favorable group in whom total abdominopelvic irradiation resulted in a 71% 10-year actuarial relapse-free survival rate compared with 40% for those treated by subtotal abdominopelvic techniques (P less than or equal to .0205). The survival improvement due to the total abdominopelvic technique in favorable patients became even more significant (P less than or equal to 0.003) after adjusting for differences in stage, grade, and postoperative residual disease volume (no, or favorable, gross). Increasing grade appeared to be associated with decreasing survival even among favorable patients treated with the optimal technique, although the differences did not approach statistical significance after adjusting for residual disease volume and stage. Surgical bowel complications were equivalent, 7.1% for total abdominopelvic v 8.1% for subtotal abdominopelvic techniques. The addition of intraperitoneal radioactive chromic phosphate increased the surgical bowel complication rate 33% over external pelvic irradiation alone without improving survival. Patients with unfavorable gross residual disease and/or FIGO stages III-B and IV were incurable by any radiation technique. Those with no, or favorable, gross residual tumor constitute a group in whom we believe open-field total abdominopelvic irradiation represents a potentially curative therapy modality.

Malignant testicular germ cell tumors in a father and two sons. Case report and literature review.

The authors report the 17th case of primary malignant testicular tumors in father-son pairs, the 61st case occurring in male first-degree relatives, and the first case identified in a father and two sons. The father had bilateral seminomas at ages 31 and 44 years. His oldest son developed left testicular teratoma with elements of seminoma and embryonal carcinoma at age 29 years. The second son developed pure seminoma of the right testicle at age 26 years. The father had mumps orchitis at age 17 years. None of the three had a history of cryptorchism, trauma, or hernia. Literature reports of familial testicular neoplasia are becoming more frequent, and evidence is presented that family history may represent a risk factor independent of cryptorchism for the development of testicular cancer. Aggressive follow-up of closely-related male relatives is advocated.

The xylanase system of Coniophora cerebella.

1. The culture filtrate of the fungus Coniophora cerebella grown on poplar 4-O-methylglucuronoxylan as carbon source and enzyme inducer contained an enzyme system that degraded the polysaccharide to xylose, acidic and neutral oligosaccharides and an enzyme-resistant polymer. Free uronic acid was not produced. 2. Cold ethanol fractionation of the culture filtrate yielded two active fractions, one of which had only xylanase (EC 3.2.1.8) and the other both xylanase and xylosidase (EC 3.2.1.37) activities. Further fractionation on DEAE-cellulose resolved the xylanase and xylosidase activities. 3. The xylanase degraded poplar 4-O-methylglucuronoxylan in an essentially random manner, producing oligosaccharides, but some xylose residues in the vicinity of uronic acid side groups were protected from hydrolysis, preventing a truly random attack. The xylosidase attacked the polysaccharide very slowly, releasing xylose, but the oligosaccharides produced by the action of the xylanase were much more susceptible to hydrolysis by the xylosidase. 4. The products of xylanase action were separated into neutral and acidic fractions. The neutral oligosaccharides were separated by chromatography on charcoal-Celite, and the major products were characterized as xylobiose, xylotriose, xylotetraose and xylopentaose. Some of the acidic sugars were branched, having the uronic acid residue attached to a xylose residue other than the terminal non-reducing one. 5. Gel filtration of various xylanase fractions gave values for the molecular weight of the enzyme from 34000 to 38000.