A phase I/II trial of three-dimensionally planned concurrent boost radiotherapy and protracted venous infusion of 5-FU chemotherapy for locally advanced rectal carcinoma.

BACKGROUND: Improving the response to preoperative therapy may increase the likelihood of successful resection of locally advanced rectal cancers. Historically, the pathologic complete response (pCR) rate has been < approximately 10% with preoperative radiation therapy alone and < approximately 20% with concurrent chemotherapy and radiation therapy. METHODS AND MATERIALS: Thirty-seven patients were enrolled on a prospective Phase I/II protocol conducted jointly at Washington University, St. Louis and the Catholic University of the Sacred Heart, Rome evaluating a three-dimensionally (3D) planned boost as part of the preoperative treatment of patients with unresectable or recurrent rectal cancer. Preoperative treatment consisted of 4500 cGy in 25 fractions over 5 weeks to the pelvis, with a 3D planned 90 cGy per fraction boost delivered once or twice a week concurrently (no time delay) with the pelvic radiation. Thus, on days when the boost was treated, the tumor received a dose of 270 cGy in one fraction while the remainder of the pelvis received 180 cGy. When indicated, nonaxial beams were used for the boost. The boost treatment was twice a week (total boost dose 900 cGy) if small bowel could be excluded from the boost volume, otherwise the boost was delivered once a week (total boost dose 450 cGy). Patients also received continuous infusion of 5-fluorouracil (1500 mg/m(2)-week) concurrently with the radiation as well as postoperative 5-FU/leucovorin. RESULTS: All 37 patients completed preoperative radiotherapy as planned within 32--39 elapsed days. Twenty-seven underwent proctectomy; reasons for unresectability included persistent locally advanced disease (6 cases) and progressive distant metastatic disease with stable or smaller local disease (4 cases). Actuarial 3-year survival was 82% for the group as a whole. Among resected cases the 3-year local control and freedom from disease relapse were 86% and 69%, respectively.Twenty-four of the lesions (65%) achieved an objective clinical response by size criteria, including 9 (24%) with pCR at the primary site (documented T0 at surgery). The most important factor for pCR was tumor volume: small lesions with planning target volume (PTV) < 200 cc showed a 50% pCR rate (p = 0.02). There were no treatment associated fatalities. Nine of the 37 patients (24%) experienced Grade 3 or 4 toxicities (usually proctitis) during preoperative treatment. There were an additional 7 perioperative and 2 late toxicities. The most important factors for small bowel toxicity (acute or late) were small bowel volume (> or = 150 cc at doses exceeding 4000 cGy) and large tumor (PTV > or = 800 cc). For rectal toxicity the threshold is PTV > or = 500 cc. CONCLUSION: 3D planned boost therapy is feasible. In addition to permitting the use of nonaxial beams for improved dose distributions, 3D planning provides tumor and normal tissue dose-volume information that is important in interpreting outcome. Every effort should be made to limit the treated small bowel to less than 150 cc. Tumor size is the most important predictor of response, with small lesions of PTV < 200 cc most likely to develop complete responses.

Colorectal cancer: risk factors and recommendations for early detection.

Spurred by mounting evidence that the detection and treatment of early-stage colorectal cancers and adenomatous polyps can reduce mortality, Medicare and some other payors recently authorized reimbursement for colorectal cancer screening in persons at average risk for this malignancy. A collaborative group of experts convened by the U.S. Agency for Health Care Policy and Research has recommended screening for average-risk persons over the age of 50 years using one of the following techniques: fecal occult blood testing each year, flexible sigmoidoscopy every five years, fecal occult blood testing every year combined with flexible sigmoidoscopy every five years, double-contrast barium enema every five to 10 years or colonoscopy every 10 years. Screening of persons with risk factors should begin at an earlier age, depending on the family history of colorectal cancer or polyps. These recommendations augment the colorectal cancer screening guidelines of the American Academy of Family physicians. Recent advances in genetic research have made it possible to identify persons at high risk for colorectal cancer because of an inherited predisposition to develop this malignancy. These patients require aggressive screening, usually by lower endoscopy performed at an early age. In some patients, genetic testing can guide screening and may be cost-effective.

UCH/RNID single channel extracochlear implant: results in thirty profoundly deafened adults.

The University College Hospital/Royal National Institute for the Deaf (UCH/RNID) Cochlear Implant Programme has now given single channel extracochlear implants to forty profoundly deafened adults. Audiological, psychophysical, speech perceptual and subjective results for the first thirty cases are described. The main findings can be summarised as follows: 1. Users of the single channel extracochlear implant gained considerable improvements in their lipreading and communication ability, as assessed by both objective testing and by the patients' own reports. All acquired useful awareness of environmental sounds and an improvement in their quality of life; some also showed improvements in their own speech. A small number were capable of some open-set speech discrimination without lipreading. 2. Extracochlear implantation was not found to destroy residual hearing, although it did cause slight deterioration in hearing thresholds in some cases. 3. Our results so far suggest that patients deafened by meningitis are likely to obtain less benefit from a single channel cochlear implant than those deafened by other causes. Better results were also achieved by younger, more recently deafened patients and those who were good lipreaders. Despite the emergence of these trends we have not yet found a reliable way to predict benefit from an implant on the basis of preoperative variables. 4. Self-reported measures of the benefits of the implant correlated well with the objective test results, but also revealed important information that was not available from the objective tests. In particular, they showed that the improvement in lipreading provided by the implant was reduced in noisy conditions.