Tumor and normal tissue dosimetry changes during MR-guided pulsed-dose-rate (PDR) brachytherapy for cervical cancer.

BACKGROUND AND PURPOSE: To analyze systematic changes in tumor and normal tissue anatomy and dosimetry using serial MR imaging during pulsed dose rate brachytherapy (PDR BT) for cervical cancer. MATERIAL AND METHODS: Forty-three patients with cervical cancer underwent MR-guided PDR BT using an intrauterine applicator alone after external beam radiotherapy. MR imaging was repeated on days 2 and 3 of treatment and the day 1 plan was applied to the re-contoured volumes. RESULTS: The mean uterine volume and mean HR CTV increased during treatment. This resulted in a decrease in the mean HR CTV D90 relative to the day 1 planned dose. There was no change in the mean bladder volume during treatment but the mean rectal volume increased. This correlated with an increase in the mean rectal dose. There were four local recurrences. There was no apparent relationship between either the planned or the delivered HR CTV D90 and local recurrence. There was only one case of late bladder toxicity but nine patients developed late rectal toxicity. The cumulative rectal dose during treatment was a better predictor of late rectal toxicity than the planned dose. CONCLUSIONS: Significant changes in tumor and normal tissue anatomy and dosimetry can occur during PDR BT and should be tracked and corrected using serial imaging and plan adaptation, especially when the day 1 tumor or normal tissue doses are close to the planning constraints.

The efficacy of hyperbaric oxygen therapy in the treatment of medically refractory soft tissue necrosis after penile brachytherapy.

PURPOSE: Soft tissue necrosis is reported in up to 26% of patients undergoing radiotherapy for penile cancer. Management options include local irrigation, wound debridement, antibiotics, anti-inflammatory medication, and analgesics. Refractory lesions may be treated with partial penectomy. Hyperbaric oxygen therapy (HBO) has a well-defined role in the treatment of late radiation toxicities. We present experience with HBO for medically refractory soft tissue necrosis after penile brachytherapy. METHODS AND MATERIALS: From November 2001 to January 2009, 7 men of 43 treated with penile brachytherapy for squamous carcinoma developed refractory soft tissue necrosis and were treated with HBO. All had received a prescribed dose of 60 Gy through interstitial brachytherapy using Paris system guidelines. All had failed conservative medical therapies for soft tissue necrosis. RESULTS: Median age was 55 years (range, 35-72 years). Comorbidities potentially effecting wound healing included hypertension (2), current smokers (5), former smoker (1) but no diabetes mellitus, or peripheral vascular disease. Median time between completion of brachytherapy and appearance of soft tissue necrosis was 13 months (range, 9-24 months) and the median interval before starting HBO was 7.5 months (range, 3-13 months). The median number of "dives" per HBO course was 40 (30-53). All 7 experienced an excellent response with healing of the necrosis and resolution of symptoms, although 3 required an additional course, 2 for consolidation of healing, and 1 for a relapse 4 months later. No patient was submitted to penectomy. CONCLUSIONS: HBO should be considered as a treatment option in patients with refractory soft tissue necrosis of the penis after brachytherapy.

3D MR-spectroscopic imaging assessment of metabolic activity in the prostate during the PSA "bounce" following 125iodine brachytherapy.

PURPOSE: A temporary increase in prostate-specific antigen (PSA) values is observed in 30%-40% of men following (125)I brachytherapy (BT) for prostate cancer. We present the results of a study to characterize prostate metabolic activity during the PSA "bounce" and to correlate metabolic changes with PSA levels using three-dimensional magnetic resonance spectroscopic imaging (3D-MRSI). METHODS AND MATERIALS: 3D-MRSI was performed in 24 patients during the PSA bounce. Eight of these had also had a baseline 3D-MRSI scan before BT for the purpose of tumor mapping. The 3D-MRSI was repeated at 6- and 12-month intervals, and PSA levels were monitored every 3 months. Twenty-one of the patients had favorable-risk prostate cancer, and 3 had intermediate risk. RESULTS: The choline+creatine signal intensity, although markedly reduced, was observable following BT. Diffuse activity not corresponding to original biopsy-positive sites was observed in 22 cases, and 2 cases were documented to have local recurrence. No statistically significant correlation between metabolic activity and PSA levels at each interval was found. CONCLUSION: Post-BT prostate 3D-MRSI shows evidence of diffuse metabolic activity unrelated to residual malignancy. This supports the benign nature of the PSA bounce and suggests an inflammatory etiology. In the situation of a rising PSA, observation of focal activity on MRI/3D-MRSI could be a useful adjunct to suggest local recurrence at an earlier interval after brachytherapy when prostate biopsies would still be unhelpful. Longer follow-up is necessary to confirm the complex relationship between metabolic activity and PSA levels.

Penile brachytherapy: technical aspects and postimplant issues.

PURPOSE: Squamous carcinoma (SCC) of the penis affects about 1 in 100,000 men in western societies. Interstitial brachytherapy can be an effective penis-conserving modality for T1, T2, and selected T3 tumors. Unfortunately, few radiation oncology trainees have the opportunity to treat a case of penile cancer during their residency, and few centers have brachytherapy expertise for this tumor site. We report our technique that has been developed and refined over the past 20 years. MATERIALS AND METHODS: From 1989 to 2009, we have been using brachytherapy to treat penile SCC and have experience with 75 cases. From 1989 to 1998, manual afterloading was used with (192)Ir wire or seeds, and from 1999 to the present, pulse dose rate automated afterloading. Sixty Gray is delivered over a period of 4-5 days. RESULTS: Patient selection for penile brachytherapy and the technical and dosimetric aspects of the procedure will be discussed along with posttreatment care and followup. CONCLUSIONS: Brachytherapy is an effective treatment for T1, T2, and selected T3 SCC of the penis. Efficacy depends on careful planning and appreciation of dosimetry.

Magnetic resonance imaging-guided intracavitary brachytherapy for cancer of the cervix.

PURPOSE: To determine the feasibility and benefits of optimized magnetic resonance imaging (MRI)-guided brachytherapy (BT) for cancer of the cervix. METHODS AND MATERIALS: A total of 20 patients with International Federation of Gynecology and Obstetrics Stage IB-IV cervical cancer had an MRI-compatible intrauterine BT applicator inserted after external beam radiotherapy. MRI scans were acquired, and the gross tumor volume at diagnosis and at BT, the high-risk (HR) and intermediate-risk clinical target volume (CTV), and rectal, sigmoid, and bladder walls were delineated. Pulsed-dose-rate BT was planned and delivered in a conventional manner. Optimized MRI-based plans were developed and compared with the conventional plans. RESULTS: The HR CTV and intermediate-risk CTV were adequately treated (the percentage of volume treated to >or=100% of the intended dose was >95%) in 70% and 85% of the patients with the conventional plans, respectively, and in 75% and 95% of the patients with the optimized plans, respectively. The minimal dose to the contiguous 2 cm(3) of the rectal, sigmoid, and bladder wall volume was 16 +/- 6.2, 25 +/- 8.7, and 31 +/- 9.2 Gy, respectively. With MRI-guided BT optimization, it was possible to maintain coverage of the HR-CTV and reduce the dose to the normal tissues, especially in patients with small tumors at BT. In these patients, the HR percentage of volume treated to >or=100% of the intended dose approached 100% in all cases, and the minimal dose to the contiguous 2-cm(3) of the rectum, sigmoid, and bladder was 12-32% less than with conventional BT planning. CONCLUSION: MRI-based BT for cervical cancer has the potential to optimize primary tumor dosimetry and reduce the dose to critical normal tissues, particularly in patients with small tumors.

Improving quality assurance for assembled COMS eye plaques using a pinhole gamma camera.

A quality assurance system has been designed to verify the location and strength of seeds loaded in a brachytherapy eye plaque. This system consists of (1) a pinhole camera in conjunction with a Lumisys ACR-2000i computed radiography (CR) unit to image the location and measure the relative strength of the seeds with autoradiography, and (2) a source strength jig with a survey meter to estimate the total activity of the seeds in the plaque. Five holders of different sizes were made for fixation of the COMS (Collaborative Ocular Melanoma Study) plaques (12, 14, 16, 18, and 20 mm) in the camera. The plaque-to-pinhole distance (dpp) has been optimized to be 30 mm to give approximately uniform intensity on the CR image for uniformly loaded COMS plaques. The pinhole-to-detector distance (dpd) can be kept at either 30 mm for 1:1 scale, or at larger distances for higher magnification. For a 1:1 scaling and pinhole diameter of 0.345 mm, useful images are obtained with time-activity product (mCi sec) ranging from 5 to 250 mCi sec. Within this range, the pinhole system is able to differentiate seed activities of >10%. The resulting pinhole autoradiograph is able to (1) confirm the correct number of seeds loaded in the plaque, (2) verify the proper sitting of the seeds in the silastic carrier and the plaque, (3) verify the relative activity distribution of the seeds loaded in the plaque, and (4) potentially evaluate the integrity of the seed. The source strength measurement system is able to measure the total strength of seeds in the plaque ranging from 10 to 80 mCi with an uncertainty of 5%.

The effect of changing technique, dose, and PTV margin on therapeutic ratio during prostate radiotherapy.

PURPOSE: To quantify the dosimetric and radiobiological changes seen when using intensity-modulated radiation therapy (IMRT) or planning target volume (PTV) margin reduction with consistent planning parameters in a representative sample of localized prostate cancer patients. METHODS AND MATERIALS: Twenty patients were randomly selected from a cohort that received 79.8 Gy using six-field conformal radiotherapy. Using the clinical contours, PTV margin, planning system, and dose constraints, five-field IMRT plans were generated for 79.8, 83.8, and 88.0 Gy. The 88.0-Gy IMRT plan was then reoptimized with a PTV margin reduced to 3 mm. These plans were then compared using various dosimetric and radiobiological endpoints calculated for various alpha/beta. RESULTS: Intensity-modulated RT resulted in greater conformity to the PTV (p < 0.001). No improvement in mean normal tissue complication probabilities in the rectal wall (NTCPrw) was seen, and the modified therapeutic ratio (TR(mod)) was largely unchanged between six-field conformal and IMRT for the majority of the patients. When IMRT was used to escalate dose, NTCPrw increased by 9% at each 5% prescription increase (p < 0.001). Reducing the posterior PTV margin from 7 mm to 3 mm for an IMRT plan reduced the mean NTCPrw by 12% (p < 0.001) and resulted in a trend toward increased TR(mod)(p = 0.005). Changes in TR(mod) between conformal and IMRT planning or PTV reduction showed large interpatient variability. CONCLUSIONS: Changing from conformal to IMRT, or from PTV(10-7) to PTV(3), did not produce a uniform interpatient increase in TR(mod)when the CTV contained the prostate alone. Radiobiological benefits of these two methods seem to be dependent on the particular anatomy of individual patients, supporting the use of patient-specific margin, planning, and dose prescription strategies.

Comparison of late toxicity between continuous low-dose-rate and pulsed-dose-rate brachytherapy in cervical cancer patients.

PURPOSE: To compare survival and severe late radiation toxicity between patients who received continuous low-dose-rate (LDR) brachytherapy (BT) and pulsed-dose-rate (PDR) BT for cervical cancer. METHODS AND MATERIALS: A retrospective review of cervical cancer patients who underwent primary radiotherapy with or without concurrent cisplatin was performed. Late Grade 3 or worse toxicities were assessed using the National Cancer Institute Common Toxicity Criteria. The study endpoints were overall and disease-free survival and the probability of severe late toxicity. RESULTS: A total of 109 patients (65.7%) received LDR BT and 57 (34.3%) received PDR BT. Seventy patients received concurrent chemotherapy with cisplatin. The 3-year overall survival and disease-free survival rate was 70% and 57% for the LDR group and 82% and 70% for the PDR group, respectively (p = 0.25 and p = 0.19). The 3-year probability rate for late Grade 3 or worse toxicity was 7.4% for LDR BT patients and 7.6% for PDR BT patients, respectively (p = 0.69) and 6.9% and 7.6%, respectively, for concurrent chemotherapy vs. none (p = 0.69). CONCLUSION: No difference was found in severe late toxicity, overall survival, or disease-free survival between the LDR and PDR groups.

Penile brachytherapy: results for 49 patients.

PURPOSE: To report results for 49 men with squamous cell carcinoma (SCC) of the penis treated with primary penile interstitial brachytherapy at one of two institutions: the Ottawa Regional Cancer Center, Ottawa, and the Princess Margaret Hospital, Toronto, Ontario, Canada. METHODS AND MATERIALS: From September 1989 to September 2003, 49 men (mean age, 58 years; range, 22-93 years) had brachytherapy for penile SCC. Fifty-one percent of tumors were T1, 33% T2, and 8% T3; 4% were in situ and 4% Tx. Grade was well differentiated in 31%, moderate in 45%, and poor in 2%; grade was unspecified for 20%. One tumor was verrucous. All tumors in Toronto had pulsed dose rate (PDR) brachytherapy (n = 23), whereas those in Ottawa had either Iridium wire (n = 22) or seeds (n = 4). Four patients had a single plane implant with a plastic tube technique, and all others had a volume implant with predrilled acrylic templates and two or three parallel planes of needles (median, six needles). Mean needle spacing was 13.5 mm (range, 10-18 mm), mean dose rate was 65 cGy/h (range, 33-160 cGy/h), and mean duration was 98.8 h (range, 36-188 h). Dose rates for PDR brachytherapy were 50-61.2 cGy/h, with no correction in total dose, which was 60 Gy in all cases. RESULTS: Median follow-up was 33.4 months (range, 4-140 months). At 5 years, actuarial overall survival was 78.3% and cause-specific survival 90.0%. Four men died of penile cancer, and 6 died of other causes with no evidence of recurrence. The cumulative incidence rate for never having experienced any type of failure at 5 years was 64.4% and for local failure was 85.3%. All 5 patients with local failure were successfully salvaged by surgery; 2 other men required penectomy for necrosis. The soft tissue necrosis rate was 16% and the urethral stenosis rate 12%. Of 8 men with regional failure, 5 were salvaged by lymph node dissection with or without external radiation. All 4 men with distant failure died of disease. Of 49 men, 42 had an intact and tumor-free penis at last follow-up or death. The actuarial penile preservation rate at 5 years was 86.5%. CONCLUSIONS: Brachytherapy is an effective treatment for T1, T2, and selected T3 SCC of the penis. Close follow-up is mandatory because local failures and many regional failures can be salvaged by surgery.

The effect of voxel size on the accuracy of dose-volume histograms of prostate 125I seed implants.

Cumulative dose-volume histograms (DVH) are crucial in evaluating the quality of radioactive seed prostate implants. When calculating DVHs, the choice of voxel size is a compromise between computational speed (larger voxels) and accuracy (smaller voxels). We quantified the effect of voxel size on the accuracy of DVHs using an in-house computer program. The program was validated by comparison with a hand-calculated DVH for a single 0.4-U iodine-125 model 6711 seed. We used the program to find the voxel size required to obtain accurate DVHs of five iodine-125 prostate implant patients at our institution. One-millimeter cubes were sufficient to obtain DVHs that are accurate within 5% up to 200% of the prescription dose. For the five patient plans, we obtained good agreement with the VariSeed (version 6.7, Varian, USA) treatment planning software's DVH algorithm by using voxels with a sup-inf dimension equal to the spacing between successive transverse seed implant planes (5 mm). The volume that receives at least 200% of the target dose, V200, calculated by VariSeed was 30% to 43% larger than that calculated by our program with small voxels. The single-seed DVH calculated by VariSeed fell below the hand calculation by up to 50% at low doses (30 Gy), and above it by over 50% at high doses (>250 Gy).