Treatment results of brachytherapy vs. external beam radiation therapy for intermediate-risk prostate cancer with 10-year followup.

PURPOSE: To compare 10-year treatment outcomes of brachytherapy vs. external beam radiation therapy for patients with intermediate-risk prostate cancer (IRPC). METHODS AND MATERIALS: Between 2004 and 2007, 93 IRPC patients underwent brachytherapy using iodine-125 to a dose of 145 Gy without supplemental external radiation. A retrospective comparison was performed to a contemporary cohort of 597 patients treated with external beam radiation therapy to a median dose of 75.3 Gy using a propensity score-matched analysis. RESULTS: Median followup was 7.8 years. With brachytherapy, 51.6% had Gleason score 7 vs. 72.0% for external radiation (p < 0.001). Median initial prostate-specific antigen was 8.3 for brachytherapy vs. 9.4 for external radiation (p = 0.01). Neoadjuvant androgen deprivation therapy was given in 59.5% of external radiation vs. 10.8% of brachytherapy patients (p < 0.001). The 10-year freedom from biochemical failure (FFBF) for brachytherapy was 81.7% vs. 54.5% for external radiation (p = 0.002). Unfavorable intermediate-risk patients experienced borderline significant improved FFBF with brachytherapy (p = 0.08). The 10-year freedom from salvage therapy for brachytherapy was 93.2% vs. 72.2% for external radiation (p = 0.006). There were no significant differences in distant metastases-free survival, prostate cancer-specific survival, or overall survival after adjusting for age. Multivariate analysis with propensity score matching showed that brachytherapy remained an independent predictor for improved FFBF (p = 0.007). Grade 1 and 2 late rectal complication rate was 6.5% for brachytherapy vs. 15.2% for external radiation (p = 0.02). CONCLUSIONS: Brachytherapy using iodine-125 without supplemental external radiation is a reasonable treatment option for selected IRPC patients.

Predicting pelvic lymph node involvement in current-era prostate cancer.

PURPOSE: The Roach formula [2/3 × prostate-specific antigen + (Gleason score--6) × 10], derived in 1993 during the early prostate specific antigen (PSA) screening era, has been used to predict the risk of pelvic lymph node involvement in patients with prostate cancer. In the current era of widespread PSA screening with a shift to earlier disease stages, there is evidence to suggest that the Roach score overestimates risk of nodal metastasis. This study retrospectively reviews the validity of this formula as a prediction tool. METHODS AND MATERIALS: We conducted a retrospective institutional review including men with clinical T1c-T3 prostate cancer, with baseline PSA levels and biopsy-obtained Gleason scores who underwent radical prostatectomy with pelvic node dissection from 2001 through 2009 (N = 1,022). The predicted risk of nodal involvement was calculated for each patient using the Roach formula and then compared with actual rates following surgery. RESULTS: The study included 1,022 patients; 99.6% had clinical T1c/T2 disease, with a mean of 10.3 lymph nodes surgically evaluated. Overall, 42 patients (4.1%) had nodal metastasis. For every range of scores, the Roach formula overestimates the risk of nodal involvement. Observed nodal positivity was 1%, 6.3%, 10%, 15.2%, and 16.7% for Roach scores ≤ 10%, >10%-20%, >20%-30%, >30%-40%, and >40%, respectively. The Roach score overestimates the risk by approximately 4.5-fold in patients with scores ≤ 10%, by 2.5-fold for all scores between 10% and 40%, and by 4-fold for scores >40%. CONCLUSION: The Roach formula overpredicts the risk of pelvic nodal involvement in current-era prostate cancer patients undergoing regular PSA screening and with mainly T1c/T2 disease. Contemporary patients are much less likely to have nodal involvement for a given PSA and Gleason score.

Comparison of early complications for patients with convexity and parasagittal meningiomas treated with either stereotactic radiosurgery or fractionated stereotactic radiotherapy.

OBJECTIVE: Patients with convexity and parasagittal (CPS) meningiomas treated with stereotactic radiosurgery (SRS) have been shown to be at risk for posttreatment symptomatic peritumoral edema (SPTE). We sought to analyze the pattern of this complication and compare it with the SPTE experienced in our patients treated with fractionated stereotactic radiotherapy. METHODS: From January 2003 to October 2005, 32 patients with CPS meningiomas were treated. Thirty patients with a total of 38 lesions had sufficient follow-up for analysis. Group A (n = 14) patients were treated with single fraction SRS, and Group B (n = 16) patients were treated with fractionated stereotactic radiotherapy. The lesion volume was different between the two groups with the Group B median volume (7.46 cm) being larger than that for Group A (2.84 cm) (P = 0.0008). Conversely age, follow-up, sex, prior surgical events, number of lesions, tumor location, and atypical histology did not differ between these groups. The median marginal dose for patients in Group A was 14 Gy (range, 12.5-18 Gy). For Group B, six patients received a median marginal dose of 50.4 Gy in 28 fractions, and 10 patients received a marginal dose of 25 Gy in five fractions. RESULTS: Seven of the 30 patients treated in this series developed posttreatment SPTE. The incidence of SPTE in Group A (six of 14 patients) was significantly higher than that in Group B (one of 16 patients) (P = 0.031). The median time to onset of SPTE in the six patients in Group A was 4 months. In Group B, one patient had onset of SPTE in 3 months. On univariate analysis, larger tumor volume (P = 0.0014) and tumor margin dose >14 Gy in patients undergoing SRS (P = 0.031) was associated with onset of SPTE. Age, previous surgery, and tumor location were not associated with onset of SPTE. CONCLUSION: Despite larger lesion volumes, fractionated stereotactic radiotherapy is associated with less risk of posttreatment SPTE than SRS for patients with CPS meningiomas in our series. For patients treated with SRS, smaller volume and dose <14 Gy seems to be safe. Longer follow-up will be required to compare late complications and tumor control rates in these patients.

Outcomes in treatment for intradural spinal cord ependymomas.

PURPOSE: Spinal cord ependymomas are rare tumors, accounting for <2% of all primary central nervous system tumors. This study assessed the treatment outcomes for patients diagnosed with spinal cord ependymomas within the Southern California Kaiser Permanente system. METHODS AND MATERIALS: We studied 23 patients treated with surgery with or without external beam radiotherapy (EBRT). The local and distant control rates and overall survival rates were determined. RESULTS: The overall local control, overall recurrence, and 9-year overall survival rate was 96%, 17.4%, and 63.9%, respectively. CONCLUSIONS: The results of our study indicate that en bloc gross total resection should be the initial treatment, with radiotherapy reserved primarily for postoperative cases with unfavorable characteristics such as residual tumor, anaplastic histologic features, or piecemeal resection. Excellent local control and overall survival rates can be achieved using modern microsurgical techniques, with or without local radiotherapy.

Accelerated partial breast irradiation using the MammoSite device: early technical experience and short-term clinical follow-up.

The MammoSite brachytherapy system is a novel form of intracavitary accelerated partial breast irradiation (APBI) that allows treatment over a 5- to 7-day course after breast conserving surgery (BCS). Fifty-one patients with invasive breast carcinoma underwent BCS and APBI using the MammoSite device, with 30 (59%) patients having drain placement in the lumpectomy cavity. Main outcome measures included time to initiating APBI, cosmesis using the Harvard Scale, and local and distant tumor recurrence with short-term follow-up. Five (9.8%) devices were explanted because of unfavorable final pathological findings or infection. Mean time to the start of APBI in patients without drain placement was 7.2 days (range, 5-12 days) compared with 5.1 days (range, 3-8 days) in patients with drains (P = 0.003). Cosmetic results were excellent in 25 (54.3%) patients, good in 19 (41.3%) patients, and fair in 2 (4.4%) patients. With a mean follow-up of 16 months (range, 6-38 months), no ipsilateral breast recurrences developed in any of the 51 patients. Thirteen patients had at least a 2-year follow-up. Two patients developed brain metastases and died at 19 and 23 months, respectively. The favorable short-term outcomes support further studies comparing APBI with standard whole-breast irradiation in patients undergoing BCS.

Breast conserving surgery and accelerated partial breast irradiation using the MammoSite system: initial clinical experience.

HYPOTHESIS: Balloon catheter-based accelerated partial breast irradiation (APBI) may result in desirable short-term outcomes in patients undergoing breast conserving surgery. DESIGN: Prospective consecutive case series. SETTING: Tertiary multidisciplinary referral center. PATIENTS: Forty selected patients with invasive breast carcinoma undergoing breast conserving surgery and MammoSite device placement. INTERVENTIONS: Breast conserving surgery, sentinel and/or axillary node dissection, placement of the new balloon catheter applicator (MammoSite device), and APBI. MAIN OUTCOME MEASURES: Infection, early and late seroma, device explantation, time to initiating APBI, acute toxic effects on the skin, and cosmesis using the Harvard Scale. RESULTS: Thirty-nine patients underwent MammoSite device placement at the time of lumpectomy; 1 patient underwent percutaneous device placement after lumpectomy. Nineteen patients (49%) had drainage catheters placed in the breast cavity at the time of lumpectomy. Wound infection developed in 3 patients (8%). Five devices (12%) were explanted because of unfavorable final pathological findings or infection. The mean time to the start of APBI in patients who did not undergo simultaneous drain placement was 7.2 days (range, 5-12 days), compared with 5.1 days (range, 3-8 days) in patients who did (P = .008). With a mean follow-up of 13.3 months (range, 2-28 months), patients completing APBI had limited toxic effects on the skin, with excellent or good cosmetic results in 39 patients (97%). CONCLUSIONS: Use of the MammoSite system in APBI has favorable short-term outcomes. Infection and radiation treatment delay are common and may warrant use of perioperative antibiotics and drain placement, respectively. A small number of patients who have device placement at the time of lumpectomy will require explantation because of unfavorable final pathological findings. Short-term outcomes of MammoSite brachytherapy support further studies comparing APBI with standard whole breast irradiation in patients undergoing breast conserving surgery.

Treatment of T3 and T4 anal carcinoma with combined chemoradiation and interstitial 192Ir implantation: a 10-year experience.

PURPOSE: To report our experience in treating T3 and T4 anal carcinoma with combined external beam (EBRT) and chemotherapy, followed by interstitial (192)Ir implant boost. METHODS AND MATERIALS: From 1990 to 2000, 31 patients with T3 and T4 anal carcinoma were treated with: 30 Gy EBRT (2 Gy fractions, 5 days/week) + 5-fluorouracil + mitomycin-C. Median implant dose was 31.3 Gy at 0.5 cm, delivered at a mean rate of 0.52 Gy/h. RESULTS: Six patients had local persistence and 4 eventually developed local-regional recurrence. Eight underwent abdomino-perineal resection (APR). With the addition of APR in selected cases, the ultimate local-regional control after initial treatment was 84%. Distant metastases occurred in 10. Of the initial cohort, 55% is still alive and NED. Eight had radiation proctitis and 7 developed postimplant ulceration. Only 1 required surgical intervention. CONCLUSIONS: Treatment of T3 and T4 anal cancer with combined chemotherapy and EBRT, followed by interstitial implant results in an ultimate local-regional control of 84%, after the inclusion of selected APR. It is well tolerated, with acceptable toxicity.

Metastatic squamous cell carcinoma of the neck from an unknown primary: management options and patterns of relapse.

PURPOSE: Management of squamous cell carcinoma of undetermined primary tumors in the head and neck region is controversial. Here we report the Southern California Kaiser Permanente experience with these patients. METHODS AND MATERIALS: From January 1969 through December 1994, 106 patients were eligible for this retrospective analysis. Distribution of nodal staging was as follows: 14 N1, 27 N2A, 39 N2B, 2 N2C, and 24 N3. Initial treatment included excisional biopsy alone in 12, radical neck dissection alone in 29, radiotherapy alone in 24, excisional biopsy followed by radiotherapy in 15, and radical neck dissection plus postoperative radiation in 26 patients. RESULTS: Except for two patients, all patients have had a minimum follow-up of 5 years. Overall, 57 patients (54%) have had recurrences. Only two patients (3%) who had received radiotherapy as part of their initial treatment had an appearance of a potential primary site inside the irradiated field vs 13 patients (32%) who had not received radiotherapy (p =.006). Combined modality therapy resulted in fewer neck relapses, particularly in patients with advanced neck disease. Including salvage, surgery alone as the initial treatment resulted in 81% ultimate tumor control above the clavicle for patients with N1 and N2a disease without extracapsular extension. The 5-year survival for the entire population was 53%. Radiotherapy alone resulted in poor survival in patients with advanced/unresectable neck disease. No significant difference in survival based on the initial treatment was found. The statistically significant adverse factors in determining survival included advanced nodal stage and the presence of extracapsular extension. CONCLUSIONS: Radiotherapy is very effective in reducing the rate of appearance of a potential primary site. However, in the absence of advanced neck disease (N1 and N2A without extracapsular extension), radiotherapy can be reserved for salvage. Radiotherapy alone results in poor outcomes in patients with advanced/unresectable neck disease, and incorporation of concurrent chemotherapy and cytoprotective agents should be investigated.

Optimal foraging: food patch depletion by ruddy ducks.

I studied the foraging behavior of ruddy ducks (Oxyura jamaicensis) feeding on patchily distributed prey in a large (5-m long, 2-m wide, and up to 2-m deep) aquarium. The substrate consisted of a 4x4 array of wooden trays (1.0-m long, 0.5-m wide, and 0.1-m deep) which contained 6 cm of sand. Any tray could be removed from the aquarium and "loaded" with a known number of prey. One bird foraged in the aquarium at a time; thus, by removing a food tray after a trial ended and counting the remaining prey, I calculated the number of prey consumed by the bird. I designed several experiments to determine if ruddy ducks abandoned a food patch in a manner consistent with the predictions of a simple, deterministic, patch depletion model. This model is based on the premise that a predator should maximize its rate of net energy intake while foraging. To accomplish this, a predator should only remain in a food patch as long as its rate of energy intake from that patch exceeds the average rate of intake from the environment. In the majority of comparisons, the number of food items consumed by the ruddy ducks in these experiments was consistent with the predictions of the foraging model. When the birds did not forage as predicted by the model, they stayed in the patch longer and consumed more prey than predicted by the model. An examination of the relation between rate of net energy intake and time spent foraging in the food patch indicated that by staying in a patch longer than predicted, the ruddy ducks experienced only a small deviation from maximum rate of net energy intake. These results provided quantitative support for the prediction that ruddy ducks maximize their rate of net energy intake while foraging.