Patients (pts) with BCVH have poor outcomes. We previously reported an ORR of 37% in 19 patients with BCVH for the combination of nivo+ipi. Herein, we report the analysis of the fully accrued BCVH cohorts. (NCT 03333616).

To determine any differences in patient satisfaction for breast cancer patients treated with either external beam radiation therapy (EBRT) or accelerated partial breast radiation (APBI) via HDR brachytherapy utilizing brachytherapy catheters from several manufacturers. Charts from 2002 to 2013 (APBI) and 2012 to 2013 (EBRT) were retrospectively reviewed. All patients were given a survey with FACET breast quality of life (QOL) and patient rated breast cosmesis (1-10), nausea, pain, dyspnea, self-consciousness, and presence of lymphedema questions. Treatment details (catheter manufacturer, radiation dosing, chemotherapy, hormone manipulation, and stage) were also collected. We identified 243 APBI patients and 38 EBRT patients. Within the EBRT cohort, 25 women met departmental criteria for APBI treatment (size < 3 cm, post-menopausal). Seventeen women (68%; mean follow-up time of 7 months) treated with EBRT and seventy-eight women (32%; mean follow-up time of 16 months) treated with APBI completed the survey. Women treated with EBRT reported more nausea (p = 0.04) and lymphedema (p = 0.046) than those treated with APBI. A trend towards worse pain (p = 0.06) and more self-consciousness (p = 0.08) was also seen with EBRT. In the APBI cohort, increased duration of follow-up was significantly positively correlated with more frequent low energy (p = 0.03, R = 0.2), nausea (p = 0.003, R = 0.3), and dyspnea (p = 0.02, R = 0.3). The single lumen Mammosite balloon (LSmean score = 6/10) was found to be associated with significantly decreased cosmesis when compared to the Mammosite ML (LSmean score = 8/10; p = 0.002) and Contura (LSmean score = 9/10; p = 0.001) balloons. Furthermore, the Mammosite balloon (LSmean score = 1.1/4) was found to be associated with significantly more dyspnea when compared to the Savi (LSmean score = 0.1/4; p = 0.01) and Contura (LSmean score = 0/4; p = 0.003) devices. In the APBI cohort, older patients reported less frequent episodes of nausea (p = 0.04, R = -0.2), pain (p = 0.003, R = -0.3), and lymphedema (p = 0.04, R = -0.2). In the EBRT cohort, tumor size was significantly negatively correlated with pain (p = 0.03, R = -0.7). APBI treated patients tend to have worsening quality of life indicators with longer follow-up; however, their experience remains superior compared to a similarly matched EBRT cohort, albeit with a small N. Younger APBI patients and smaller tumors treated with EBRT had worse outcomes. Multi-lumen applicators provided superior cosmetic outcomes and less reported dyspnea.

To analyze efficacy and patient satisfaction with brachytherapy delivered accelerated partial breast radiation (APBI) in a community setting. A retrospective chart review was performed on all patients treated before October 2011 with HDR APBI. A survey was sent out to all women who were at least three months out from procedure to assess their satisfaction. Women were also asked about level of energy, nausea, pain, shortness of breath, self-consciousness, and lymphedema using FACET breast quality of life (QOL) questionnaire. This questionnaire has previously been validated. From June 2002 to September 2011, 183 women were treated with partial breast radiation using HDR APBI. Devices from a variety of manufacturers were used. A total of 22.8%, 11.4%, 23.4%, 28.8%, and 8.7% were Tis, T1a, T1b, T1c, or T2 respectively. Seven women (3.8%) had evidence of disease in a sentinel node; two N0(IHC+), two N1mic, and three N1a. Thirty women (16%) were ER- and PR-. After treatment, four women had breast cancer recurrence (one distant, one local and two local and distant). None of these women had positive nodes, all were T1-2, and two of them were triple negative. ER - disease was correlated with recurrence (p < 0.0001). Only 75 women (40%) had physician assessed cosmetic outcome at last follow-up; of these, 46% had good or excellent cosmesis while 53% had fair or poor cosmesis. Forty-six women (25%) completed satisfaction surveys. Of survey respondents: 14 (34%) reported unhappiness with cosmetic outcome with "hardness" being the most commonly cited reason. When grading their breast satisfaction on a scale of 1-10: 18% reported a score of 1-4, 38% had a score of 5-7, and 44% had a score of 8-10. Cosmetic outcomes and responses to FACET questionnaires were not correlated with duration of follow-up. With a median follow-up of 40 months, our disease control rate of (98%) is consistent with other published series of APBI. The association with ER - status and recurrence is consistent with ASBS registry data. The rate of physician and patient graded unsatisfactory cosmetic outcome is concerning, but likely due to reporting bias. The number of women reporting pain was surprising and likely related to capsule formation. A follow-up study to evaluate satisfaction with whole breast radiation therapy is planned.Poster Viewing Abstract 2001; TableFACET breast QOLN = 45Lack of energyNauseaCertain parts of my body with painShort of breathSelf-conscious with way I dressOne or both arms are swollen or tenderNot at all23613233741A little bit2356951Somewhat10311821Quite a bit719411Very much306101 Open table in a new tab

Purpose: Normal tissuedose tolerance for hypofractionated radiotherapy is under active investigation. Previous radiation increases the complexity of determining the dose limits. We developed a software tool to optimize CyberKnife treatment planning for patient specific dose tolerances using the linear quadratic (LQ) model to derive biologically effective doses (BED) and to correlate these findings with observed toxicities. Methods: A program was written in Visual Basic using LQ model to estimate the normal organ BED tolerance for hypofractionated radiotherapy. Total tolerance BED was derived from the literature on conventional fractionated radiotherapy. For patients who previously received radiation from other modalities and fractionation schemes, prior doses were converted to equivalent BED and subtracted. Based on these calculations, physicians set dose constraints for organs at risk (OAR) to optimize the treatment plan. Plan re‐optimization was required until the plan dose was less than 90% of the dose constraint for each OAR. 259 consecutive patients treated with CyberKnife radiosurgery at our institution since 2007 to 2010 were retrospectively reviewed. Treatment related toxicities were evaluated according to CTCAE for 208 out of 259 patients who had available follow‐up data. Results: Guided by this software tool, plan re‐optimizations were routinely performed for most patients (193/208 patients or 93%). 60 patients (29%) received previous radiation treatment. High grade early toxicities were observed in 4 patients (4 or 1.9% in grade 3, no grade 4 or 5). All high grade toxicities were related to the OAR identified in the planning process. Conclusions: This software provides an essential tool to appropriately optimize hypofractionated radiotherapy. The LQ model and BED dose evaluations appear to be a safe method to obtain normal tissue tolerances for these patients, with toxicity rates comparable to conventional fractionation. The BED subtraction method properly set the optimization objectives for patients treated with different fractionation schemes.

PURPOSE:Stereotactic body radiation therapy (SBRT) has emerged as a treatment option for local tumor control of primary and secondary malignancies of the liver. We report on our updated experience with SBRT in patients with non-resectable tumors of the liver.METHODS:Our first 17 consecutive patients (mean age 58.1 years) receiving SBRT for HCC (n = 6), IHC (n = 3), and LM (n = 8) are presented. Mean radiation dose was 34 Gy delivered over 1-3 fractions.RESULTS:Treated patients had a mean decrease in maximum pretreatment tumor diameter from 6.9 +/- 4.6 cm to 5.0 +/- 2.1 cm at three months after treatment (P < .05). The mean total tumor volume reduction was 44% at six months (P < .05). 82% of all patients (14/17) achieved local control with a median follow-up of 8 months. 100% of patients with HCC (n = 6) achieved local control. Patients with surgically placed fiducial markers had no complications related to marker placement.CONCLUSION:Our preliminary results showed that SBRT is a safe and effective local treatment modality in selected patients with liver malignancies with minimal adverse events. Further studies are needed to define its role in the management of these malignancies.

Transperineal ultrasound guided prostate seed brachytherapy (PSI) is a common procedure performed for the long-term control of prostate cancer. After the completion of the procedure, a cystoscopy is often performed to ensure that no seeds were inadvertently introduced into the bladder. After the patient recovers, he is generally given a trial of voiding. If the patient cannot urinate or has significant urinary retention, a Foley catheter is generally replaced, and the patient is sent home with the catheter for 1-2 weeks to allow for a decrease in prostatic edema. Published studies have shown differences in urinary symptoms for patients who underwent rigid versus flexible cystoscopy outside of the setting of PSI. Here, we investigate possible factors including cystoscopy that may contribute to urinary toxicity, the most common form of toxicity in patients receiving PSI. A retrospective chart review was performed for 62 consecutive patients who received PSI at our institution from 12/2006 to 9/2009. Possible contributing factors were collected: whether or not cystoscopy was performed and type of cystoscopy, prostate volume, isotope type, and the number of seeds and needles used. Possible outcomes were collected: Foley catheter requirement immediately after PSI and International Prostate Symptom Score (IPSS) at the time of first follow-up (if in the first 3 months) as well as the change from the pre-procedure IPSS. There was a large and significant difference (p = 0.0000454) between rates if Foley catheter requirement after rigid cystoscopy (75.0%) versus flexible cystoscopy (17.2%) and no cystoscopy (12.5%) by Chi-square analysis. There was no statistical difference between flexible and no cystoscopy. Foley catheter requirement was not associated with prostate volume, isotope, or the number of seeds and needles. No factors were associated with post-implant IPSS. We report a strong singular association between rigid cystoscopy and Foley catheter requirement after PSI in our institutional experience. Although rigid cystoscopy is often favored by urologists for better visualization, flexible cystoscopy should be performed instead whenever possible to reduce the risk of urinary retention and Foley catheter requirement after PSI.

e16006 Background: We evaluated the initial acute toxicities experienced by patients treated with cyberknife fractionated radiosurgery for low and low-intermediate risk prostate cancer. Methods: Twenty-two patients with low or low-intermediate risk prostate cancer (T2a, GG 3+3=6 or 3+4=7, PSA <10) were enrolled prospectively on an IRB approved protocol and treated the planning target volume (PTV)(prostate+5mm margin) with cyberknife fractionated radiosurgery to a dose of 36.25 Gy in 5 fractions (7.25Gy/fraction). The target volume included the prostate and seminal vesicles. PSA values, AUA symptom scores (AUA SS), and NCI CTC acute toxicities were analyzed prior to radiosurgery and at 1 month (N=16), 3 months (N=12) and 6 months (N=5)post-treatment. Results: Patients treated on study included 12 with GG 3+3=6 cancer and 10 with GG 3+4=7 cancer. Mean patient age was 66 years old (range 49–79). Mean pre-treatment PSA was 5.29 (range 0.64–9.36) declining to 3.44 (range 0.00–10.43) at 1 month post treatment, 1.99 (range 0.31–3.99) at 3 months post-treatment and 2.08 (1.05–3.13) at 6 months post-treatment. Mean pre-treatment AUA SS was 7 (range 0.–18) increasing to 12 (range 2–29) at 1 month post treatment, decreasing to 8 (range 2–17) at 3 months post-treatment and 11 (3–17). There were 5 grade 1 acute toxicities including (diarrhea, fatigue, mild urinary frequency, hemorrhoid and a rash) and 7 grade 2 toxicities including (bladder spasms, painful urinary, bowel irregularity, rectal pain, urethritis and numbness in the upper thigh), all grade 1 and 2 toxicities resolved within three months of treatment. The one patient with grade 2 thigh numbness was not thought to be study related toxicity. Two patients developed grade 3 toxicity. One developed bacteremia after the transrectal ultrasound guided placement of the fiducials, the infection completely resolved after treatment with antibiotics. One patient on Coumadin developed hematuria which resolved with conservative management. Conclusions: Cyberknife fractionated radiosurgery for patients with early stage prostate cancer appears to be safe on our early initial assessment.Continued evaluation and longer follow-up ongoing. [Table: see text]

To determine the efficacy of a stereotactic radiosurgical boost focused only at areas of high-risk determined by MR spectroscopy functional imaging in addition to standard conventional radiotherapy for patients with glioblastoma multiforme. Thirty-five patients enrolled in this prospective Phase II trial between 2003 and 2007 underwent surgical resection or biopsy for a glioblastoma multiforme followed by gamma knife stereotactic radiosurgery directed toward areas of high biologic activity determined by MR spectroscopy (MRS) within 2 cm of the postoperative enhancing surgical bed. The MRS high-biologic activity regions were determined by dividing the T2 MRI volume into 1 cm voxels and identifying those voxels that contained an elevated Choline/NAA ratio in excess of 2:1 over baseline. These voxels were then marked and digitally fused with the radiosurgery planning MRI. The marked voxels were targeted with 8 mm isocenters. The radiosurgery dose used was based on the maximum diameter of the combined high biologic voxels with doses of 15 Gy, 18 Gy, and 24 Gy utilized for total treated voxel diameter between 3–4 cm, 2–3 cm, and 1–2 cm, respectively. All patients received conventional conformal radiotherapy after radiosurgery to a total dose of 60 Gy in 2 Gy daily fractions (46 Gy to the T2 volume with a 2 cm margin followed by a 14 Gy boost to the contrasted T1 volume with a 2.5 cm margin). The primary endpoint measured was overall survival which was measured from the date of gamma knife radiosurgical treatment to the date of death, and censored at the date of last follow-up for survivors. The Kaplan-Meier estimation of overall survival was determined for the entire cohort and for each RTOG malignant glioma RPA class. The median survival time for the entire cohort was 15.8 months (95% CI, 11–19.9 months). With 75% of RPA class 3 patients still alive 18 months after treatment; the median survival for RPA class 3 has not yet been reached. The median survivals for RPA class 4, 5, and 6 patients were 18.7 months (95% CI, 14.5–29.1 months), 12.5 months (95% CI, 9.2–18.5 months), and 3.9 months (95% CI, 2.7–5.1 months), respectively, (p < 0.0001 comparing RPA class). The RTOG trial historic control median survivals for patients with RPA class 3, 4, 5, and 6 patients treated with conformal radiotherapy alone are 17.9, 11.1, 8.9, and 4.6 months, respectively. The MR Spectroscopy targeted radiosurgery directed only to areas of high biologic activity combined with conformal brain radiotherapy for patients with glioblastoma multiforme is feasible with overall patient survivals that compare favorably to historic controls of patients treated with conformal radiotherapy alone.

Intraoperative planning for prostate seed implant (PSI) brachytherapy results in improved dosimetry with more consistent dose coverage and lower urethral and rectal doses. However, there are still no consistent recommendations for dosimetric constraints during planning. Here, we attempt to determine which parameters influence acute urinary toxicity, the most common toxicity after PSI. Between October 2005 and January 2008, 48 consecutive patients with clinical Stage T1-2a, Gleason Grade 3 + 3 = 6 or 3 + 4 = 7 prostate adenocarcinoma received ultrasound-guided PSI as monotherapy using Pd-103 (PD = 125 Gy) or I-125 (PD = 144 Gy) seeds. All patients were planned intraoperatively with prostate V100 (percent of volume receiving 100% of prescription dose) >99%, V150 <70%, V200 <42%, urethral V150 = 0% (except 1 patient), and rectal V100 = 0% (except 3 patients <1%). Prophylactic tamsulosin was prescribed post-implant and tapered down as tolerated. AUA (American Urological Association) Prostate Symptom scores were assessed before treatment and at regular intervals afterwards. Because urinary symptoms varied widely at baseline, we calculated change in AUA score 1-2 months and 3-5 months post-implant. Using linear regression, we correlated change in AUA score to treatment parameters, including the number of needles and seeds, prostate D80 (minimum dose to 80% of prostate receiving the highest dose), D90, D100, V150, V200, and urethral D80, D90, D100. There was a statistically significant correlation between prostate V200 and increase in 1-2 month post-implant AUA scores (p = 0.029) with a mean 0.55 increase in AUA score per 1% increase in prostate V200 in 45 patients with available data. Patients with prostate V200 <30% vs. >=30% had a mean AUA increase of 7.31 vs. 14.65 at 1-2 months (p = 0.021). There was a trend when comparing prostate V150 and increase in 1-2 month AUA scores that did not reach statistical significance (p = 0.348). Patients who had prostate V150s <60% vs. >=60% had a mean AUA increase of 9.33 vs. 13.85 at 1-2 months (p = 0.103). By 3-5 months, the correlations with V150 and V200 no longer existed. None of the other analyzed parameters correlated with urinary toxicity. After analyzing numerous dosimetric factors, prostate V200 was the most important parameter correlating with acute urinary morbidity. There was a dramatic reduction of an average 7.34 AUA points with prostate V200 <30%, and we recommend this as a parameter in intraoperative planning. There was a trend toward lower AUA scores with prostate V150 <60% suggesting this as a secondary constraint. To meet these goals, inverse planning solutions may be helpful in reducing high dose regions within the prostate while maintaining adequate dose coverage.

During routine Gamma Knife radiosurgery procedure, it was noted that the Automatic Positioning System (APS) (Elekta Inc) did not always function as expected for some patients This caused the plans to be readjusted for use of trunnions which greatly lengthens the treatment time in most cases. After investigation of those repeated APS operation failures, the reliability of APS was extensively tested by performing a series of measurements to determine head frame distortion. Measurements on a fabricated hard wood phantom using a range of torques (2–20 in⋅lbs) were applied to screws which fastened the head frame into the skull of the patients for Gamma knife treatment. The ability for the Leksell frame to lock into APS was used as the endpoint to determine whether the APS would operate clinically. A calibrated digital torque wrench was applied in those measurements. The magnitude of the distortion on the head frame has been measured by using calipers between the two frame members (Z-bars) which are attached to the sides of head frame bi-laterally. In the clinical application, the acceptable torque upper limit was 15 in⋅lbs which was the maximum applied to the screws in 26 clinical cases and has been used to predict the success application of the phantom measurements. For 14 Gamma Knife cases, if a frame displacement was greater than 1.5 mm, the APS would not operate. If frame displacements under 1.5 mm, the APS operated in 12 cases. A linear correlation coefficient (r2) was found to be 0.94 for the fitting of the data to a line.

Purpose: We determined the prognostic role, if any, of the ProstaScint(TM) (111)indium-capromab pendetide scan before salvage radiotherapy for biochemical recurrence after RP for localized prostate cancer.Materials and Methods: We reviewed the records of 649 patients who underwent a ProstaScint(TM) scan from 1998 to 2004. A total of 44 patients were identified who had biochemical recurrence after RP and underwent a ProstaScint(TM) scan immediately before salvage radiotherapy. All patients received salvage radiotherapy to the prostatic bed unless pelvic lymph node uptake was identified on the scan, resulting in initial whole pelvic radiotherapy with 45 Gy, followed by a conformal boost to the prostate bed in 6. The median salvage radiotherapy dose to the prostate bed was 72 Gy. Patient demographics, pathological information, PSA values and ProstaScint(TM) results were collected retrospectively. The majority of ProstaScint(TM) scans were digitally fused with noncontrast pelvic computerized tomography images for interpretation. PSA progression after radiotherapy was defined using American Society for Therapeutic Radiation and Oncology criteria.Results: At a mean followup of 22 months 43 of 44 patients (97%) experienced a PSA decrease after salvage radiotherapy with a mean PSA nadir of 0.16 ng/ml compared to a mean pre-radiotherapy PSA of 1.7 ng/ml. Of the 44 patients 15 (34%) showed post-radiotherapy PSA progression. When the entire cohort was analyzed, patients with negative ProstaScint(TM) scans had statistically lower post-radiotherapy PSA progression rates than patients with positive scans (I of 10 or 10% vs 14 of 34 or 41%, p = 0.026). Patients with negative ProstaScint(TM) results were also statistically more likely to have a pre-radiotherapy PSA of less than 1.0 ng/ml (p = 0.005), no seminal vesicle involvement (p = 0.006), a greater mean PSA doubling time (p = 0.008) and received no hormone therapy (p = 0.003). When patients with pre-radiotherapy PSA less than 1.0 ng/ml were analyzed, a negative ProstaScint(TM) scan suggested but did not provide a statistically significant advantage over pre-radiotherapy PSA alone for predicting post-radiotherapy PSA progression (1 of 9 or 11% for negative vs 5 of 15 or 33% for positive scans, p = 0.20).Conclusions: Our early experience supports an improved prognosis in patients receiving salvage pelvic radiotherapy for biochemical recurrence after RP who have a negative pre-radiotherapy ProstaScint(TM) scan. However, this finding is not necessarily independent of pre-radiotherapy PSA.

We compared prostate position corrections using ultrasound and megavoltage CT image guided systems following initial patient positioning with lasers. Internal prostate movements between the two patient cohorts were assumed to be equivalent given a sufficient number of measurements, so we hypothesize the image guided shifts should average out to the same magnitude. Therapists adjusted patient positions with physician supervision based on daily imaging prior to each treatment. A total of 17 prostate patients were studied. Ten patients (Group I) were scanned in 3‐D mode using an ultrasound system. Contours (prostate/bladder/rectum) from the treatment planning system were transposed on the image set to register the ultrasound image. Therapists shift the contours to match the ultrasound image set and then adjust the patient by these same shifts. The number of shifts recorded from Group I was 432. Group II patients (seven subjects yielding 315 recorded shifts) were treated using Tomotherapy. Patients were scanned over the prostate region and the megavoltage CT image was registered with the treatment planning CT and contours. Shifts were produced for each axes and in roll. The patient table is adjusted to match the registration shifts. Roll corrections were minor and deemed insignificant for this study. The average prostate size from Group I was 104.9cc with a standard deviation of 42.1cc while Group II was 104.2cc and 54.8cc. A panel of four was formed to evaluate the quality of images to check possible operator bias due to image quality. Group I showed an average shift magnitude of 6.1mm with a standard deviation of 3.4mm. The average shift from Group II was 10.6mm with a standard deviation of 6.1mm. Tomotherapy imaging averaged 43% larger shifts compared to ultrasound. Possible explanations for this difference include operator laxity in initial tomotherapy positioning while depending on imaging and auto‐adjustment to compensate.