Relationship between radiation treatment time and overall survival after induction chemotherapy for locally advanced head-and-neck carcinoma: a subset analysis of TAX 324.

PURPOSE: To analyze the relationship between overall survival (OS) and radiation treatment time (RTT) and overall treatment time (OTT) in a well-described sequential therapy paradigm for locally advanced head-and-neck carcinoma (LAHNC). METHODS AND MATERIALS: TAX 324 is a Phase III study comparing TPF (docetaxel, cisplatin, and fluorouracil) with PF (cisplatin and fluorouracil) induction chemotherapy (IC) in LAHNC patients; both arms were followed by carboplatin-based chemoradiotherapy (CRT). Prospective radiotherapy quality assurance was performed. This analysis includes all patients who received three cycles of IC and a radiation dose of ≥70 Gy. Radiotherapy treatment time was analyzed as binary (≤8 weeks vs. longer) and continuous (number of days beyond 8 weeks) functions. The primary analysis assessed the relationship between RTT, OTT, and OS, and the secondary analysis explored the association between treatment times and locoregional recurrence (LRR). RESULTS: A total of 333 (of 501) TAX 324 patients met the criteria for inclusion in this analysis. There were no significant differences between the treatment arms in baseline or treatment characteristics. On multivariable analysis, PF IC, World Health Organization performance status of 1, non-oropharynx site, T3/4 stage, N3 status, and prolonged RTT (hazard ratio 1.63, p=0.006) were associated with significantly inferior survival. Performance status, T3/4 disease, and prolonged RTT (odds ratio 1.68, p=0.047) were independently and negatively related to LRR on multivariable analysis, whereas PF was not. Overall treatment time was not independently associated with either OS or LRR. CONCLUSIONS: In this secondary analysis of the TAX 324 trial, TPF IC remains superior to PF IC after controlling for radiotherapy delivery time. Even with optimal IC and concurrent chemotherapy, a non-prolonged RTT is a crucial determinant of treatment success. Appropriate delivery of radiotherapy after IC remains essential for optimizing OS in LAHNC.

Androgen deprivation-mediated cytoreduction before interstitial brachytherapy for prostate cancer does not abrogate the elevated risk of urinary morbidity associated with larger initial prostate volume.

PURPOSE: We examined whether prostate volume reduction after a short course of androgen deprivation (AD) lowered the risks of acute and chronic urinary morbidity related to radioactive seed implantation for low-risk prostate cancer. METHODS AND MATERIALS: Eighty-one patients received AD for cytoreduction before interstitial brachytherapy alone. Urinary morbidity was carefully assessed for all patients during a median followup of 53 (range, 23-78) months after treatment. Outcomes were then compared with those of a control group of 81 patients who were matched 1:1 based on identical prostate volume measured at the time of radioactive seed implant, but who had not received AD. RESULTS: Despite effective cytoreduction (median, 30% prostate volume reduction) with AD, prolonged catheterization was required significantly more often for patients who had received AD when compared with the control group of patients who were implanted at identical prostate volumes but who had not received AD (27% vs. 9%, p = 0.02). This finding remained statistically significant on multivariate analysis (p = 0.04). Surgical intervention (9% vs. 4%, p = 0.09) and subsequent urinary incontinence (4% vs. 1%, p = 0.16) were also more frequent among patients who had received AD when compared with implant volume-matched controls. CONCLUSIONS: Patients who achieved smaller prostate volumes through the use of AD maintained a significantly elevated risk (threefold) for urinary complications, commensurate with their initially large prostate volume, when compared with a control group of patients who were implanted at identical prostate volumes but who had not received AD. Therefore, patients presenting with larger prostate glands that would warrant a short course of AD before implant should be counseled accordingly when discussing options for local therapy.

Real-time computed tomography dosimetry during ultrasound-guided brachytherapy for prostate cancer.

PURPOSE: Ultrasound-guided implantation of permanent radioactive seeds is a treatment option for localized prostate cancer. Several techniques have been described for the optimal placement of the seeds in the prostate during this procedure. Postimplantation dosimetric calculations are performed after the implant. Areas of underdosing can only be corrected with either an external beam boost or by performing a second implant. We demonstrate the feasibility of performing computed tomography (CT)-based postplanning during the ultrasound-guided implant and subsequently correcting for underdosed areas. METHODS AND MATERIALS: Ultrasound-guided brachytherapy is performed on a modified CT table with general anesthesia. The postplanning CT scan is performed after the implant, while the patient is still under anesthesia. Additional seeds are implanted into "cold spots," and the resultant dosimetry confirmed with CT. RESULTS: Intraoperative postplanning was successfully performed. Dose-volume histograms demonstrated adequate dose coverage during the initial implant, but on detailed analysis, for some patients, areas of underdosing were observed either at the apex or the peripheral zone. Additional seeds were implanted to bring these areas to prescription dose. CONCLUSION: Intraoperative postplanning is feasible during ultrasound-guided brachytherapy for prostate cancer. Although the postimplant dose-volume histograms for all patients, before the implantation of additional seeds, were adequate according to the American Brachytherapy Society criteria, specific critical areas can be underdosed. Additional seeds can then be implanted to optimize the dosimetry and reduce the risk of underdosing areas of cancer.

Effect of random seed placement error in permanent transperineal prostate seed implant.

BACKGROUND AND PURPOSE: Random seed placement error may adversely effect dose distribution in transperineal prostate seed implants. In this study, we investigated the extent to which individual seed activity influences dose-distribution degradation due to random seed placement error. PATIENTS AND METHODS: Separate initial treatment plans were prepared for three prostate sizes, 27.3, 43.2 and 48.9 cc, using 0.35, 0.55 and 0.75 mCi iodine-125 seeds. All stated activities are understood to be apparent activities. The combinations produced a total of nine treatment plans. Each initial treatment plan was subjected to 1000 stochastic three-dimensional Gaussian perturbations of seed location, with a standard deviation of 4mm for a total of 9000 treatment plans. The resulting plans were evaluated for target coverage and urethra involvement. RESULTS: Satisfactory initial treatment plans were prepared for all prostate sizes and seed activities. All 9000 perturbed treatment plans showed acceptable target coverage under the D90/90 criterion. Some of the perturbed plans for the 27.3 and 43.2 cc prostates with 0.55 and 0.75 mCi seeds failed the V100/90 criterion. Some of the randomly perturbed seed distributions showed significantly increased doses to the urethra relative to the unperturbed treatment plan. This effect was more pronounced with greater seed activity. CONCLUSIONS: There may be a higher probability of unfavorable target coverage due to random seed placement error when performing transperineal iodine-125 prostate seed implants using seeds with activity greater than 0.35 mCi. There may also be a higher probability of unfavorable urethra involvement when using higher activity seeds.

A comparison of the precision of seeds deposited as loose seeds versus suture embedded seeds: a randomized trial.

PURPOSE: Brachytherapy for prostate cancer with permanent low-dose-rate seeds has been shown to be an effective treatment for early stage prostate cancer. Due to the rapid falloff of dose, accurate seed placement is critical for optimal dosimetry. One approach to achieve optimal dosimetry is the use of seeds embedded in suture material. Seeds embedded in suture may not move after implantation as much as loose seeds. This would improve implant dosimetry. To evaluate this hypothesis a formal study was conducted in which half the gland was implanted with seeds embedded in suture and half with loose seeds. Final dosimetry is compared between both halves of the prostate. METHODS AND MATERIALS: Patients entered this Investigational Review Board approved prospective trial after completion of informed consent. At time of implant, the side of the gland to be implanted with loose as opposed to suture embedded seeds was randomly assigned. The patients then underwent intraoperative preplanned implantation. None of the preplans directed seed locations outside the prostate. Both the seeds embedded in suture and the loose seeds were implanted using needles with stylettes. At 4-6 weeks post implant, seed location was determined with CT. Both sides of the gland on CT were contoured and used for final dosimetric calculations. A cost function analysis was used to determine individual seed position deviation from intended to actual seed location. RESULTS: Eight patients were enrolled in the study. A total of 549 seeds were implanted; 240 seeds embedded in suture and 309 loose seeds. Prostate volumes ranged from 24.0-45.5 cc with a mean of 38.6 cc. The average radial deviation of the loose seeds from planned position was determined to be 3.1 mm compared with the average radial deviation of the suture embedded seeds of 3.7 mm. There was no improvement in the final dosimetry when suture embedded seeds where used. The D90 and V100 values for the half of the prostate implanted with suture embedded seeds were 71-140 (mean, 92.1) and 80.2-99.5 (mean, 89.6), respectively, for the half of the prostate implanted with loose seeds. (All D90, V100 values are % of prescription dose.) CONCLUSION: Seeds embedded in suture material do not lead to superior precision in seed deposition when compared with loose seeds, when implanted inside the prostate.

Real time MRI-ultrasound image guided stereotactic prostate biopsy.

To report a technique for target directed transperineal ultrasound guided biopsy using high resolution endorectal MRI images Ultrasound fusion. Two patients presented after external beam irradiation for prostate cancer with a rising PSA. An Endorectal MRI using a 1.5 Tesla scanner was obtained. Subsequently a Transrectal Ultrasound guided biopsy was performed. The Ultrasound probe was fixed to a stepper-stabilizer to provide a reference coordinate system for stereotaxic needle biopsy needle placement. The MRI image set was fused to the Ultrasound images in real time. Abnormal areas determined in the MR images were targeted for biopsy. Recurrent prostate carcinoma was detected pathologically in 3 of 4 stereotactic biopsies. Abnormal areas suspicious for cancer detected on T1 weighted images obtained in a strong field Endorectal MRI scan can be targeted for stereotactic biopsy using Transrectal Ultrasound. This image guide technique may be very useful in directing biopsies.