Phase III double-blind study of glutamine versus placebo for the prevention of acute diarrhea in patients receiving pelvic radiation therapy.

PURPOSE: A phase III, randomized, double-blind study was conducted by the North Central Cancer Treatment Group to determine the efficacy and toxicity of oral glutamine for the prevention of acute diarrhea in patients receiving pelvic radiation therapy (RT). PATIENTS AND METHODS: All 129 patients enrolled from 14 institutions between February 1998 and October 1999 were eligible. Patients received 4 g of glutamine or placebo orally, twice a day, beginning with the first or second day of RT and continuing for 2 weeks after RT. During treatment, patients were assessed weekly for toxicity, and a bowel function questionnaire was administered. The primary measures of treatment efficacy were diarrhea levels measured by maximum grade of diarrhea, incidence of diarrhea, and average diarrhea score. After completion of RT, the bowel function questionnaire was administered weekly for 4 weeks and at 12 and 24 months. Toxicity was measured by National Cancer Institute common toxicity criteria. RESULTS: The median age of patients was 69 years (range, 34 to 86 years). The two treatment arms were balanced with respect to all baseline factors. There were no significant differences in toxicity by treatment. Quality-of-life scores and the mean number of problems reported on the bowel function questionnaire were virtually identical for both treatment groups. The incidence of grade 3 or higher diarrhea was 20% for the glutamine arm and 19% for the placebo arm (P =.99). The maximum number of stools per day was 5.1 for the glutamine arm and 5.2 for the placebo arm (P =.99). CONCLUSION: There is no evidence of a beneficial effect of glutamine during pelvic RT.

A comparison of permanent prostate brachytherapy techniques: preplan vs. hybrid interactive planning with postimplant analysis.

PURPOSE: To compare preparation time, procedure time in the operating room, equipment needs, and Day 0 postimplant dosimetry between two different Mick implant techniques performed at a single institution. METHODS AND MATERIALS: One hundred consecutive monotherapy patients treated from 1999 to 2000 with 125I transperineal permanent implantation of the prostate using an afterloading Mick applicator were evaluated. The first 40 patients were treated with a preplanned modified peripheral loading Mick technique. The next 60 were treated with a hybrid interactive image-guided Mick technique. The analysis included planning the following: ultrasound volume, time required of preplanning, Day 0 CT volume, number of seeds, number of needles, activity per seed, total activity of the implant, and procedure time. Dosimetric parameters included D(90), V(100), and V(150). RESULTS: Mean planning ultrasound volume (33 vs. 37 cc), Day 0 CT volume (49 vs. 47 cc), mCi/seed (0.30 vs. 0.34 mCi/seed), number of seeds (121 vs. 96), total activity of the implant (36 vs. 32 mCi), D(90) (132 vs. 149 Gy), V(100) (86% vs. 91%), and V(150) (51% vs. 38%) were comparable. Significant differences (p < 0.01) were noted in mean preplan time (30 vs. 7 min), number of needles (32 vs. 19), and procedure time (90 vs. 40 min). CONCLUSIONS: Hybrid interactive Mick prostate brachytherapy consistently reduces preplanning time, procedure time, and number of needles used, reducing patient treatment time and costs while maintaining excellent dosimetric coverage. Use of hybrid interactive Mick prostate brachytherapy results in improved therapeutic ratios, i.e., maintains Day 0 D(90) >140 Gy, V(100) >90%, and V(150) <40%, without the need for sophisticated three-dimensional intraoperative planning technology.

A quality-adjusted reanalysis of a Phase III trial comparing once-daily thoracic radiation vs. twice-daily thoracic radiation in patients with limited-stage small-cell lung cancer(1).

PURPOSE: We undertook an analysis of quality-adjusted survival using the Q-TWiST (Quality Time Without Symptoms or Toxicity) methodology and developed a new graphic representation called a quality-adjusted life-years plot, which presents a complete and concise Q-TWiST analysis on a single plot. METHODS AND MATERIALS: The Q-TWiST plot incorporates the time without symptoms or toxicity and several combinations of utility coefficients for toxicity and relapse days into the same plot. In addition, the plot includes threshold lines, to judge whether a particular combination of utility coefficients reaches a significance level. RESULTS: The differential in toxicity incidence and severity between the two thoracic radiation treatment arms was inconsequential. Sensitivity analyses were run using Q-TWiST plots. For all combinations of the various toxicity definitions and utility coefficients, the median Q-TWiST was greater for the once-daily thoracic radiation treatment arm than for the twice-daily treatment arm, without achieved significance. CONCLUSION: This work refines the results previously reported for this Phase III clinical trial in patients with limited-stage small-cell cancer, and there was no significant difference in survival after adjusting for toxicity and progression. Furthermore, the new methods developed for this trial allow for a more detailed and parsimonious presentation of survival and toxicity data for all oncology clinical trials.

Long-term results of a phase III trial comparing once-daily radiotherapy with twice-daily radiotherapy in limited-stage small-cell lung cancer.

PURPOSE: This Phase III study was performed to determine whether twice-daily (b.i.d.) radiotherapy (RT) resulted in better survival than once-daily (q.d.) RT for patients with limited-stage small-cell lung cancer (LD-SCLC). METHODS AND MATERIALS: A total of 310 patients with LD-SCLC initially received three cycles of etoposide and cisplatin. Subsequently, the 261 patients without significant progression were randomized to two cycles of etoposide and cisplatin plus either q.d. RT (50.4 Gy in 28 fractions) or split-course b.i.d. RT (24 Gy in 16 fractions, a 2.5-week break, and 24 Gy in 16 fractions) to the chest. Patients then received a sixth cycle of etoposide and cisplatin followed by prophylactic cranial RT. RESULTS: Follow-up ranged from 4.6 to 11.9 years (median, 7.4 years). The median survival and 5-year survival rate from randomization was 20.6 months and 21% for patients who received q.d. RT compared with 20.6 months and 22% for those who received b.i.d. RT (p = 0.68), respectively. No statistically significant differences were found in the rates of progression (p = 0.68), intrathoracic failure (p = 0.45), in-field failure (p = 0.62), or distant failure (p = 0.82) between the two treatment arms. No statistically significant difference was found in the overall rate of Grade 3 or worse (p = 0.83) or Grade 4 or worse toxicity (p = 0.95). Grade 3 or worse esophagitis (p = 0.05) was more common in the b.i.d. arm. Grade 5 toxicity occurred in 4 (3%) of 130 patients who received b.i.d. RT compared with 0 (0%) of 131 who received q.d. RT (p = 0.04). CONCLUSION: Although this study did not demonstrate an advantage to split-course b.i.d. RT, the long-term survival was favorable, likely reflecting the positive influences of concurrent combined modality therapy and prophylactic cranial RT.

Image guided I125 prostate brachytherapy with Hybrid Interactive Mick technique in the community setting: How does it compare?

The aim of this study is to evaluate the target coverage, procedural techniques, and merits of Hybrid Interactive Mick (HIM) I125 transperineal permanent implantation (TPPI) of the prostate performed with 10 urologists in a community hospital. Detailed day 0 post-implant dosimetric evaluations of TPPI procedures were performed on 333 consecutive monotherapy patients treated between September 2000 and November 2003 at a single institution. All patients underwent TPPI with HIM. Pelvic and CXR films were obtained for a manual seed count at day 0 and again > day 90 on 175 patients. The HIM-prostate brachytherapy performed in a community hospital provided median D(90), V100, and V150 values of 157Gy, 94%, and 42.3%, respectively. 18% of patients had seed migration to the lungs while 2% had seed migration to the bladder. Only 7 patients (4%) had 2 or more seeds migrate to the lungs. Procedure times average 38 minutes and number of needles used averaged 18. The post-implant urinary retention rate was 2.1% Use of HIM-prostate brachytherapy in the community setting with multiple urologists reproducibly maintained excellent and consistent dosimetric coverage. Procedure times and number of needles used were minimized, and with careful attention to image-guided technique, seed migration to bladder and lung was also minimized.

A survey of current clinical practice in permanent and temporary prostate brachytherapy: 2010 update.

PURPOSE: To help establish patterns of care and standards of care of interstitial permanent low-dose-rate (LDR) and temporary high-dose-rate brachytherapy for prostate cancer and to compare the results with a similar 1998 American Brachytherapy Society (ABS) survey. METHODS AND MATERIALS: A comprehensive questionnaire intended to survey specific details of current clinical brachytherapy practice was provided to the participants of the seventh ABS Prostate Brachytherapy School. Responses were tabulated and descriptive statistics are reported. RESULTS: Sixty-five brachytherapy practitioners responded to the survey. Eighty-nine percent (89%) of respondents performed LDR and 49% perform high-dose-rate brachytherapy. The median number of years of experience for LDR brachytherapists increased from 5 to 10 years over the course of the 12 years since the preceding survey. Compared with the first ABS, a smaller proportion of respondents received formal brachytherapy residency training (43% vs. 56%) or formal "hands-on" brachytherapy training (15% vs. 63%). There has been a marked decline in the utilization of the Mick applicator (Mick Radio-Nuclear Instruments, Inc., Mount Vernon, NY, USA) (60% vs. 28%) and an increase in the use of stranded seeds (40% vs. 11%). Compliance with postimplant dosimetry was higher in the 2010 survey. CONCLUSION: This survey does suggest an evolution in the practice of LDR brachytherapy since 1998 and aids in identifying aspects that require further progress or investigation. ABS guidelines and other practice recommendations appear to impact the practice of brachytherapy.

AnchorSeed for the reduction of source movement in prostate brachytherapy with the Mick applicator implant technique.

PURPOSE: The purpose of this study was to evaluate the influence of potential contributing factors to the incidence of seed slippage and quality of prostate brachytherapy dosimetry comparing "coated" vs. "bare" seeds with a Mick applicator. METHODS AND MATERIALS: Two consecutive groups of 89 patients were treated with (125)I prostate brachytherapy at a high treatment volume single institution. All the patients were evaluated with Day 0 plain films of the pelvis and CT-based dosimetry analysis. The incidence of seed slippage was quantified. The seed slippage outcome was evaluated with respect to source type (bare vs. coated). The Day 0 prostate V(100), V(150), D90%, rectal V(100), and urethra D(30) outcomes were evaluated with respect to source type. RESULTS: A total of 13,512 seeds were placed in 178 patients. An average of 76 seeds and 16 needles were used for each patient. The bare seed group was significantly higher on fluoroscopy minutes (2.34 vs. 1.58 min), seed slippage (5 vs. 1.5 mm), volume of rectum receiving 100% of dose (0.05 vs. 0.0 cc), dose percentage received by 30% of urethra (119% vs. 113.64%), and volume of prostate receiving 100% of prescription dose (95.21% vs. 92.8%). No significant differences in volume of prostate receiving 150% of prescription dose, dose percentage received by 90% of prostate, vascular seed migration, or operating room procedure time were seen. No seed drift greater than 10mm outside the "packet" of other seeds was seen in the AnchorSeed (BrachySciences, a division of Biocompatibles, Inc. Oxford, CT) cohort. CONCLUSION: The report is the first to show the unique "fixity" of AnchorSeed to remain in position after deployment from the Mick applicator. Minimizing seed drag can reduce dose to the penile bulb, and maximize radiation coverage to the apex of the gland.