Adjuvant radiation therapy in uterine carcinosarcoma: A population-based analysis of patient demographic and clinical characteristics, patterns of care and outcomes.

OBJECTIVE: To examine clinical and demographic characteristics of a population-based cohort of patients with uterine carcinosarcoma (UCS), to assess access to treatment and survival patterns. METHODS: Surveillance, Epidemiology and End Results database was queried for patients diagnosed in 1999-2010 and treated with surgery with or without adjuvant radiation therapy (aRT). The Kaplan-Meier method was used to estimate survival functions, and Cox proportional hazards regression - to analyze the effect of covariates on survival. RESULTS: 2342 patients were eligible. African Americans presented with more advanced AJCC stages than other races (35.4% vs. 29.1%; p<0.01). African Americans vs. others, and women diagnosed in 1999-2004 vs. in 2005-2010, received aRT at a similar rate: 36.5% vs. 39.9% (p=NS), and 39.5% vs. 38.9% (p=NS), respectively. There was a trend towards higher aRT utilization among patients younger than 65 vs. older (41.4% vs. 37.5%; p<0.06). We observed better overall and cause-specific survival in the aRT group: 42 vs. 22 (p<0.0001) and 57 vs. 28months (p<0.0001), respectively. Black race, diagnosis in 1999-2004, advanced stage and age≥65years carried a higher risk of UCS death. CONCLUSIONS: We observed greater survival rate in the aRT group. African Americans were more likely to present with later stage disease and die of UCS than non-African Americans. Age and stage, but not race, influenced receipt of aRT. Patients treated more recently survived longer.

The cost-effectiveness of surgical resection and cesium-131 intraoperative brachytherapy versus surgical resection and stereotactic radiosurgery in the treatment of metastatic brain tumors.

This study aims to evaluate the cost-effectiveness of surgical resection (S) and Cesium-131 (Cs-131) [S + Cs-131] intraoperative brachytherapy versus S and stereotactic radiosurgery (SRS) [S + SRS] for the treatment of brain metastases. Treatment records as well as hospital and outpatient charts of 49 patients with brain metastases between 2008 and 2012 who underwent S + Cs-131 (n = 24) and S + SRS (n = 25) were retrospectively reviewed. Hospital charges were compared for the single treatment in question. Means and curves of survival time were defined by the Kaplan-Meier estimator, with the cost analysis focusing on the time period of the relevant treatment. Quality adjusted life years (QALY) and Incremental cost-effectiveness ratios (ICER) were calculated for each treatment option as a measure of cost-effectiveness. The direct hospital costs of treatments per patient were: S + Cs131 = $19,271 and S + SRS = $44,219. The median survival times of S + Cs-131 and S + SRS were 15.5 and 11.3 months, and the 12 month survival rates were 61 % and 49 % (P = 0.137). The QALY for S + SRS when compared to S + Cs-131 yielded a p < 0.0001, making it significantly more cost-effective. The ICER also revealed that when compared to S + Cs-131, S + SRS was significantly inferior (p < 0.0001). S + Cs-131 is more cost-effective compared with S + SRS based on hospital charges as well as QALYs and ICER. Cost effectiveness, in addition to efficacy and risk, should factor into the comparison between these two treatment modalities for patients with surgically resectable brain metastases.

Tissue compliance meter is a more reproducible method of measuring radiation-induced fibrosis than late effects of normal tissue-subjective objective management analytical in patients treated with intracavitary brachytherapy accelerated partial breast irradiation: results of a prospective trial.

Identification of radiation-induced fibrosis (RIF) remains a challenge with Late Effects of Normal Tissue-Subjective Objective Management Analytical (LENT-SOMA). Tissue compliance meter (TCM), a non-invasive applicator, may render a more reproducible tool for measuring RIF. In this study, we prospectively quantify RIF after intracavitary brachytherapy (IB) accelerated partial breast irradiation (APBI) with TCM and compare it with LENT-SOMA. Thirty-nine women with American Joint Committee on Cancer Stages 0-I breast cancer, treated with lumpectomy and intracavitary brachytherapy delivered by accelerated partial breast irradiation (IBAPBI), were evaluated by two raters in a prospective manner pre-IBAPBI and every 6 months post-IBAPBI for development of RIF, using TCM and LENT-SOMA. TCM classification scale grades RIF as 0 = none, 1 = mild, 2 = moderate, and 3 = severe, corresponding to a change in TCM (ΔTCM) between the IBAPBI and nonirradiated breasts of ≤2.9, 3.0-5.9, 6.0-8.9, ≥9.0 mm, respectively. LENT-SOMA scale employs clinical palpation to grade RIF as 0 = none, 1 = mild, 2 = moderate, and 3 = severe. Correlation coefficients-Intraclass (ICC), Pearson (r), and Cohen's kappa (κ)-were employed to assess reliability of TCM and LENT-SOMA. Multivariate and univariate linear models explored the relationship between RIF and anatomical parameters [bra cup size], antihormonal therapy, and dosimetric factors [balloon diameter, skin-to-balloon distance (SBD), V150, and V200]. Median time to follow-up from completion of IBAPBI is 3.6 years (range, 0.8-4.9 years). Median age is 69 years (range, 47-82 years). Median breast cup size is 39D (range, 34B-44DDD). Median balloon size is 41.2 cc (range, 37.6-50.0 cc), and median SBD is 1.4 cm (range, 0.2-5.5 cm). At pre-IBAPBI, TCM measurements demonstrate high interobserver agreement between two raters in all four quadrants of both breasts ICC ≥ 0.997 (95% CI 0.994-1.000). After 36 months, RIF is graded by TCM scale as 0, 1, 2, and 3 in 10/39 (26%), 17/39 (43%), 9/39 (23%), and 3/39 (8%) of patients, respectively. ΔTCM ≥6 mm (moderate-severe RIF) is statistically different from ΔTCM ≤3 mm (none-mild RIF) (p < 0.05). At 36 months post-IBAPBI, TCM measurements for two raters render ICC = 0.992 (95% CI 0.987-0.995) and r = 0.983 (p < 0.0001), whereas LENT-SOMA demonstrates κ = 0.45 (95% CI 0.18-0.80). SBD and V150 are the only factors closest to 0.05 significance of contributing to RIF. This prospective study indicates that TCM is a more reproducible method than LENT-SOMA in measuring RIF in patients treated with IBAPBI. This tool renders a promising future application in assessing RIF.

Assessment of pain as a sequela in patients treated with intracavitary brachytherapy accelerated partial breast irradiation (IBAPBI): preliminary results of a prospective study.

To assess pain rates and relationship to radiation-induced fibrosis (RIF) in patients treated with intracavitary brachytherapy accelerated partial breast irradiation (IBAPBI). Thirty-nine patients treated with IBAPBI were assessed prospectively for development of pain pretreatment, 1 month post-IBAPBI, and every 6 months thereafter. A qualitative subjective Late Effects of Normal Tissue-Subjective Objective Management Analytical (LENT-SOMA) questionnaire assessed pain. Use of pain medications was assessed as "no", "sometimes", or "regularly". A quantitative objective validated pressure threshold (PTH) measured pain in the site of IBAPBI breast (index) and its mirror-image in the nonirradiated breast (control). A validated tissue compliance meter (TCM) quantitatively assessed RIF in the index and control breasts at all time points. Mean ΔPTH(kg) and ΔTCM(mm) values reflected mean difference between the index and control breasts. Median follow-up is 44 months (range 5-59 months). According to LENT-SOMA, pain occurred in 89% at 1 and 24 months, 67% at 30 months, 30% at 36 months, 29% at 40 months, and 20% at 48 months. No patient used pain medication "regularly" but the use "sometimes" decreased over time: 61% at 1 month, 42% at 18 and 24 months, 13% at 36 months, and 10% at 40 months. Mean ΔPTH values, compared to Δ0 kg at baseline, peaked in absolute value by 1 month to -1.36 kg (p < 0.0001), persisted after 18 months at -0.99 kg (p < 0.0001) and 24 months at -0.73 kg (p < 0.0001), and returned to nearly baseline by 40 months at -0.11 kg (p < 0.57). Mean ΔPTH and ΔTCM correlated significantly with subjective patient reports of pain at each time point (p < 0.0001). To date, this is the first report to prospectively assess pain employing quantitative and qualitative inventories in patients treated with IBAPBI. Pain is experienced in the majority of patients experienced pain within the first 2 years, sometimes requiring a medication, and though subsides, it may persist 4 years after IBAPBI.

Down-regulation of microRNA 106b is involved in p21-mediated cell cycle arrest in response to radiation in prostate cancer cells.

BACKGROUND: microRNAs (miRNAs) are endogenous short non-coding RNAs, and play a pivotal role in regulating of a variety of cellular processes, including proliferation and apoptosis, both of which are cellular responses to radiation treatment. The purpose of this study is to identify candidate miRNAs whose levels are altered in response to radiation in prostate cancer cells and to investigate the molecular pathway of such miRNAs in the regulation of radiation-induced cellular response. METHODS: Using a miRNA microarray assay, we screened 132 cancerous miRNAs in LNCaP cells in response to radiation treatment. The function of one candidate miRNA was investigated for checkpoint protein expression, cell cycle arrest, cell proliferation, and cell survival in cells transfected with precursor or antisense miRNA. RESULTS: In response to radiation, multiple miRNAs, including mi-106b, showed altered expression. Cells transfected with precursor miR-106b were able to suppress radiation-induced p21 activation. Functionally, exogenous addition of precursor miR-106b overrode the G2/M arrest in response to radiation and resulted in a transient diminishment of radiation-induced growth inhibition. CONCLUSION: We have shown a novel role of miR-106b, in the setting of radiation treatment, in regulating the p21-activated cell cycle arrest. Our finding that miR-106b is able to override radiation-induced cell cycle arrest and cell growth inhibition points to a potential therapeutic target in certain prostate cancer cells whose radiation resistance is likely due to consistently elevated level of miR-106b.

A 10-year follow-up of treatment outcomes in patients with early stage breast cancer and clinically negative axillary nodes treated with tangential breast irradiation following sentinel lymph node dissection or axillary clearance.

We compare long-term outcomes in patients with node negative early stage breast cancer treated with breast radiotherapy (RT) without the axillary RT field after sentinel lymph node dissection (SLND) or axillary lymph node dissection (ALND). We hypothesize that though tangential RT was delivered to the breast tissue, it at least partially sterilized occult axillary nodal metastases thus providing low nodal failure rates. Between 1995 and 2001, 265 patients with AJCC stages I-II breast cancer were treated with lumpectomy and either SLND (cohort SLND) or SLND and ALND (cohort ALND). Median follow-up was 9.9 years (range 8.3-15.3 years). RT was administered to the whole breast to the median dose of 48.2 Gy (range 46.0-50.4 Gy) plus boost without axillary RT. Chi-square tests were employed in comparing outcomes of two groups for axillary and supraclavicular failure rates, ipsilateral in-breast tumor recurrence (IBTR), distant metastases (DM), and chronic complications. Progression-free survival (PFS) was compared using log-rank test. There were 136/265 (51%) and 129/265 (49%) patients in the SLND and ALND cohorts, respectively. The median number of axillary lymph nodes assessed was 2 (range 1-5) in cohort SLND and 18 (range 7-36) in cohort ALND (P < 0.0001). Incidence of AFR and SFR in both cohorts was 0%. The rates of IBTR and DM in both cohorts were not significantly different. Median PFS in the SLND cohort is 14.6 years and 10-year PFS is 88.2%. Median PFS in the ALND group is 15.0 years and 10-year PFS is 85.7%. At a 10-year follow-up chronic lymphedema occurred in 5/108 (4.6%) and 40/115 (34.8%) in cohorts SLND and ALND, respectively (P = 0.0001). This study provides mature evidence that patients with negative nodes, treated with tangential breast RT and SLND alone, experience low AFR or SFR. Our findings, while awaiting mature long-term data from NSABP B-32, support that in patients with negative axillary nodal status such treatment provides excellent long-term cure rates while avoiding morbidities associated with ALND or addition of axillary RT field.

Seroma is an expected consequence and not a complication of MammoSite brachytherapy.

Seroma has long been listed as a complication of MammoSite brachytherapy. Palpable abnormalities are clinically apparent months after treatment and a vast majority of patients demonstrate seroma formation in radiologic studies. We embarked on this study to evaluate the actual sonographic incidence and eventual sonographic resolution, possible contributing factors, cosmesis, pain, and local control associated with seroma formation after MammoSite partial breast irradiation (PBI). We investigated 160 patients who underwent MammoSite PBI from 2002 to 2006 of whom 100 patients had serial sonographic information. Clinical and tumor variables, infection, pain, and cosmesis were investigated. Dosimetric data including volume of balloon, dose at balloon surface, and at skin were analyzed. After a median follow-up of 36 months, the incidence of sonographically confirmed post-radiation seroma was 78% within the first 1 year following radiation and steadily decreased with time. The average size of a seroma cavity was 2.3 cm (range 0.6-6 cm) with a decline to an average of 1.4 cm after 1 year, with complete resolution in 65% of patients at 2 years. No statistically significant correlation was found between patient characteristics, tumor variables, and volumetric or dosimetric data for seroma formation. Excellent/good cosmetic scores were achieved in 94% of women with and 92% without seroma. Local control was equivalent between patients with and without seroma. Consecutive sonographic imaging reveals a high rate of seroma formation after MammoSite PBI, with resolution in 65% of patients by 2 years without intervention. Seroma formation does not prevent an excellent cosmetic result or alter local control.

Prostate and seminal vesicle volume based consideration of prostate cancer patients for treatment with 3D-conformal or intensity-modulated radiation therapy.

PURPOSE: The purpose of this article was to determine the suitability of the prostate and seminal vesicle volumes as factors to consider patients for treatment with image-guided 3D-conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT), using common dosimetry parameters as comparison tools. METHODS: Dosimetry of 3D and IMRT plans for 48 patients was compared. Volumes of prostate, SV, rectum, and bladder, and prescriptions were the same for both plans. For both 3D and IMRT plans, expansion margins to prostate+SV (CTV) and prostate were 0.5 cm posterior and superior and 1 cm in other dimensions to create PTV and CDPTV, respectively. Six-field 3D plans were prepared retrospectively. For 3D plans, an additional 0.5 cm margin was added to PTV and CDPTV. Prescription for both 3D and IMRT plans was the same: 45 Gy to CTV followed by a 36 Gy boost to prostate. Dosimetry parameters common to 3D and IMRT plans were used for comparison: Mean doses to prostate, CDPTV, SV, rectum, bladder, and femurs; percent volume of rectum and bladder receiving 30 (V30), 50 (V50), and 70 Gy (V70), dose to 30% of rectum and bladder, minimum and maximum point dose to CDPTV, and prescription dose covering 95% of CDPTV (D95). RESULTS: When the data for all patients were combined, mean dose to prostate and CDPTV was higher with 3D than IMRT plans (P < 0.01). Mean D95 to CDPTV was the same for 3D and IMRT plans (P > 0.2). On average, among all cases, the minimum point dose was less for 3D-CRT plans and the maximum point dose was greater for 3D-CRT than for IMRT (P < 0.01). Mean dose to 30%, rectum with 3D and IMRT plans was comparable (P > 0.1). V30 was less (P < 0.01), V50 was the same (P > 0.2), and V70 was more (P < 0.01) for rectum with 3D than IMRT plans. Mean dose to bladder was less with 3D than IMRT plans (P < 0.01). V30 for bladder with 3D plans was less than that of IMRT plans (P < 0.01). V50 and V70 for 3D plans were the same for 3D and IMRT plans (P > 0.2). Mean dose to femurs was more with 3D than IMRT plans (P < 0.01). For a given patient, mean dose and dose to 30% rectum and bladder were less with 3D than IMRT plans for prostate or prostate+SV volumes <65 (38/48) and 85 cm3 (39/48), respectively (P < 0.01). The larger the dose to rectum or bladder with 3D plans, the larger also was the dose to these structures with IMRT (P < 0.001). For both 3D and IMRT plans, dose to rectum and bladder increased with the increase in the volumes of prostate and seminal vesicles (P < 0.02 to 0.001). CONCLUSIONS: Volumes of prostate and seminal vesicles provide a reproducible and consistent basis for considering patients for treatment with image-guided 3D or IMRT plans. Patients with prostate and prostate+SV volumes <65 and 85 cm3, respectively, would be suitable for 3D-CRT. Patients with prostate and prostate+SV volumes >65 and 85 cm3, respectively, might get benefit from IMRT.

Influence of volumes of prostate, rectum, and bladder on treatment planning CT on interfraction prostate shifts during ultrasound image-guided IMRT.

PURPOSE: The purpose of this study was to analyze the relationship between prostate, bladder, and rectum volumes on treatment planning CT day and prostate shifts in the XYZ directions on treatment days. METHODS: Prostate, seminal vesicles, bladder, and rectum were contoured on CT images obtained in supine position. Intensity modulated radiation therapy plans was prepared. Contours were exported to BAT-ultrasound imaging system. Patients were positioned on the couch using skin marks. An ultrasound probe was used to obtain ultrasound images of prostate, bladder, and rectum, which were aligned with CT images. Couch shifts in the XYZ directions as recommended by BAT system were made and recorded. 4698 couch shifts for 42 patients were analyzed to study the correlations between interfraction prostate shifts vs bladder, rectum, and prostate volumes on planning CT. RESULTS: Mean and range of volumes (cc): Bladder: 179 (42-582), rectum: 108 (28-223), and prostate: 55 (21-154). Mean systematic prostate shifts were (cm, +/-SD) right and left lateral: -0.047 +/- 0.16 (-0.361-0.251), anterior and posterior: 0.14 0.3 (-0.466-0.669), and superior and inferior: 0.19 +/- 0.26 (-0.342-0.633). Bladder volume was not correlated with lateral, anterior/posterior, and superior/inferior prostate shifts (P > 0.2). Rectal volume was correlated with anterior/posterior (P < 0.001) but not with lateral and superior/inferior prostate shifts (P > 0.2). The smaller the rectal volume or cross sectional area, the larger was the prostate shift anteriorly and vice versa (P < 0.001). Prostate volume was correlated with superior/inferior (P < 0.05) but not with lateral and anterior/posterior prostate shifts (P > 0.2). The smaller the prostate volume, the larger was prostate shift superiorly and vice versa (P < 0.05). CONCLUSIONS: Prostate and rectal volumes, but not bladder volumes, on treatment planning CT influenced prostate position on treatment fractions. Daily image-guided adoptive radiotherapy would be required for patients with distended or empty rectum on planning CT to reduce rectal toxicity in the case of empty rectum and to minimize geometric miss of prostate.

Quantitative assessment of radiation-induced fibrosis of the breast with tissue compliance meter, palpation, and radiological imaging: preliminary results.

Quantification of radiation (RT)-induced fibrosis (RIF) continues to present a challenge in breast cancer survivors. We compare assessment of RIF by palpation and tissue compliance meter (TCM) to the radiological findings in women treated with RT. Of 300 patients treated with adjuvant RT, 17 women had > or =2-year follow-up sufficient to document RIF. Palpation and TCM were employed by three radiation oncologists in a blinded fashion. Palpation grades 1, 2, and 3 denoted mild, moderate, and severe RIF. TCM measured degree of compliance (DC) of RIF in irradiated (RTB) and nonirradiated breasts (NRTB). Architectural distortions (AD) on mammograms, ultrasound (US), and MRI were assessed. Median time of follow up was 3.9 years (range 2.1-6.5 years). Palpation revealed RIF grades 1, 2, and 3 in four, 10, and three patients, respectively. Mean percent changes (PC) in DC between RTB and NRTB by TCM were 19.5%, 37.1%, and 57.5% for grades 1, 2, and 3 RIF, respectively (p < 0.0001). There was a strong linear correlation between palpation grade and PC of DC by TCM (spearman-rank correlation=0.88, p < 0.0001). Interobserver variability (reliability) was computed using intraclass correlation coefficient (ICC) for TCM and kappa statistic for clinical palpation (ICC=0.99 [p < 0.0001] and kappa=0.70 [p < 0.0001], respectively). There was no correlation between average size of the AD as measured by the imaging modalities and RIF as assessed by palpation or TCM. Our preliminary data suggest that quantification of RIF is best with TCM. TCM results correlate better with palpation than with radiological imaging. The study with larger number of patients required to confirm our findings is underway.

Older Patients With Early-stage Breast Cancer: Adjuvant Radiation Therapy and Predictive Factors for Cancer-related Death.

PURPOSE: Studies have shown that older women are undertreated for breast cancer. Few data are available on cancer-related death in elderly women aged 70 years and older with pathologic stage T1a-b N0 breast cancer and the impact of prognostic factors on cancer-related death. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried for women aged 70 years or above diagnosed with pT1a or pT1b, N0 breast cancer who underwent breast conservation surgery from 1999 to 2003. The Kaplan-Meier survival analysis was performed to evaluate breast cause-specific survival (CSS) and overall survival (OS), and the log-rank test was employed to compare CSS/OS between different groups of interest. Multivariable analysis (MVA), using Cox proportional hazards regression analysis, was performed to evaluate the independent effect of age, race, stage, grade, ER status, and radiation treatment on CSS. Adjusted hazard ratios were calculated from the MVA and reflect the increased risk of breast cancer death. Competing-risks survival regression was also performed to adjust the univariate and multivariable CSS hazard ratios for the competing event of death due to causes other than breast cancer. RESULTS: Patients aged 85 and above had a greater risk of breast cancer death compared with patients aged 70 to 74 years (referent category) (adjusted hazard ratio [HRs]=1.98). Race had no effect on CSS. Patients with stage T1bN0 breast cancer had a greater risk of breast cancer death compared with stage T1aN0 patients (adjusted HR=1.35; P=0.09). ER negative patients had a greater risk of breast cancer death compared with ER positive patients (adjusted HR=1.59; P<0.017). Patients with higher grade tumors had a greater risk of breast cancer death compared with patients with grade 1 tumors (referent category) (adjusted HRs=1.69 and 2.96 for grade 2 and 3, respectively). Patients who underwent radiation therapy had a lower risk of breast cancer death compared with patients who did not (adjusted HR=0.55; P<0.0001). CONCLUSIONS: Older patients with higher grade, pT1b, ER-negative breast cancer had increased risk of breast cancer-related death. Adjuvant radiation therapy may provide a CSS benefit in this elderly patient population.

Radiation Exposure and Safety Precautions Following 131Cs Brachytherapy in Patients with Brain Tumors.

Cesium-131 (Cs) brachytherapy is a safe and convenient treatment option for patients with resected brain tumors. This study prospectively analyzes radiation exposure in the patient population who were treated with a maximally safe neurosurgical resection and Cs brachytherapy. Following implantation, radiation dose rate measurements were taken at the surface, 35 cm, and 100 cm distances. Using the half-life of Cs (9.69 d), the dose rates were extrapolated at these distances over a period of time (t = 30 d). Data from dosimetry badges and rings worn by surgeons and radiation oncologists were collected and analyzed. Postoperatively, median dose rate was 0.2475 mSv h, 0.01 mSv h, and 0.001 mSv h and at 30 d post-implant, 0.0298 mSv h, 0.0012 mSv h, and 0.0001 mSv h at the surface, 35 cm, and 100 cm, respectively. All but one badge and ring measured a dose equivalent corresponding to ~0 mSv h, while 1 badge measured 0.02/0.02/0.02 mSv h. There was a significant correlation between the number of seeds implanted and dose rate at the surface (p = 0.0169). When stratified by the number of seeds: 4-15 seeds (n = 14) and 20-50 seeds (n = 4) had median dose rates of 0.1475 mSv h and 0.5565 mSv h, respectively (p = 0.0015). Using National Council on Radiation Protection guidelines, this study shows that dose equivalent from permanent Cs brachytherapy for the treatment of brain tumors is limited, and it maintains safe levels of exposure to family and medical personnel. Such information is critical knowledge for the neurosurgeons, radiation oncologists, nurses, hospital staff, and family as this method is gaining nationwide popularity.

Single course IMRT plan to deliver 45 Gy to seminal vesicles and 81 Gy to prostate in 45 fractions.

We treat prostate and seminal vesicles (SV) to 45 Gy in 25 fractions (course 1) and boost prostate to 81 Gy in 20 more fractions (course 2) with Intensity Modulated Radiation Therapy (IMRT). This two-course IMRT with 45 fractions delivered a non-uniform dose to SV and required two plans and two QA procedures. We used Linear Quadratic (LQ) model to develop a single course IMRT plan to treat SV to a uniform dose, which has the same biological effective dose (BED) as that of 45 Gy in 25 fractions and prostate to 81 Gy, in 45 fractions. Single course IMRT plans were compared with two-course IMRT plans, retrospectively for 14 patients. With two-course IMRT, prescription to prostate and SV was 45 Gy in 25 fractions and to prostate only was 36 Gy in 20 fractions, at 1.8 Gy/fraction. With 45-fraction single course IMRT plan, prescription to prostate was 81 Gy and to SV was 52 or 56 Gy for a alpha/beta of 1 and 3, respectively. 52 Gy delivered in 45 fractions has the same BED of 72 Gy3 as that of delivering 45 Gy in 25 fractions, and is called Matched Effective Dose (MED). LQ model was used to calculate the BED and MED to SV for alpha/beta values of 1-10. Comparison between two-course and single course IMRT plans was in terms of MUs, dose-max, and dose volume constraints (DVC). DVC were: 95% PTV to be covered by at least 95% of prescription dose; and 70, 50, and 30% of bladder and rectum should not receive more than 40, 60, and 70% of 81 Gy. SV Volumes ranged from 2.9-30 cc. With two-course IMRT plans, mean dose to SV was non-uniform and varied between patients by 48% (54 to 80 Gy). With single-course IMRT plan, mean dose to SV was more uniform and varied between patients by only 9.6% (58.2 to 63.8 Gy), to deliver MED of 56 Gy for alpha/beta - 1. Single course IMRT plan MUs were slightly larger than those for two-course IMRT plans, but within the range seen for two-course plans (549-959 MUs, n=51). Dose max for single-course plans were similar to two-course plans. Doses to PTV, rectum and bladder with single course plans were as per DVC and comparable to two-course plans. Single course IMRT plan reduces IMRT planning and QA time to half.

Clinical comparison of brachytherapy versus hypofractionated external beam radiation versus standard fractionation external beam radiation for non-melanomatous skin cancers.

PURPOSE: Non-melanomatous skin cancer (NMSC) is the single most common cancer in the US. Radiation therapy is an excellent treatment alternative to surgery. High-dose-rate (HDR) brachytherapy and external beam radiotherapy (EBRT) are commonly used radiation treatment modalities but little data is published comparing these modalities. We present our institution's experience and outcomes with these therapeutic options. MATERIAL AND METHODS: From June 2005 to March 2013, 61 patients were treated with HDR brachytherapy (n = 9), hypofractionated EBRT (n = 30), or standard fractionation EBRT (n = 22) for NMSC. The primary outcome measure was local control at most remote follow-up and secondary outcome measures were overall survival, cosmetic outcome, and toxicity. Univariate analysis was performed to compare outcomes between treatment modalities. Kaplan-Meier analysis and log-rank test were used to compare overall survival. RESULTS: Median follow-up was 30 months. The most common histologies were BCC (47%) and SCC (44%); mean patient age was 83.3 years. Local control was 81% and 2-year actuarial overall survival was 89%. There was no statistical difference in local control or overall survival between treatment modalities. There was no statistical difference in cosmetic outcome or toxicity between treatment modalities, although five of six "poor" cosmetic outcomes and the only grade 3 toxic events were found in the standard fractionation EBRT group. CONCLUSIONS: All modalities investigated represent effective treatments for NMSC and have good cosmetic outcomes and acceptable toxicity profiles. The finding of higher grade toxicity and a greater portion of patients experiencing toxicity among standard fractionation therapy is counter to expectations. There was no statistical significance to the finding and it is not likely to be meaningful.

Adjuvant Pelvic Radiation Therapy±Vaginal Brachytherapy in Patients With High-risk Stage I or Stage II Uterine Papillary Serous, Clear Cell, and High-grade Endometrioid Carcinoma.

PURPOSE: Radiation therapy (RT) for stages I-II uterine papillary serous carcinoma (UPSC), clear cell (CC), and high-grade endometrioid (HGE) carcinoma present a treatment challenge. Regimens include external beam radiotherapy (EBRT) with or without brachytherapy. We examine the use of these radiation modalities in these endometrial cancers (EC) with respect to cause-specific survival (CSS). METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients with AJCC stages I-II UPSC, CC, or HGE cancer treated with hysterectomy and RT between 1998 and 2008. Patients who did not receive adjuvant RT or received brachytherapy alone were excluded. CSS was evaluated by the Kaplan-Meier survival analysis and the log-rank test was used to compare CSS. Multivariate analysis was performed using the Cox proportional hazards regression model. Adjusted hazard ratios (HR) were calculated for risk of EC death. RESULTS: There were 1653 patients included in this analysis. The overall 100-month CSS for the entire cohort was 81.0%. The 100-month CSS was 85.3% for EBRT alone and 86.5% for EBRT+brachytherapy (P=0.72). Stage IC/IIA/IIB patients had a greater risk of EC death compared with stage IA/IB patients (adjusted HR=2.39; P<0.0001). Patients with UPSC and CC had a slightly higher risk of EC death compared with HGE (adjusted HR=1.01 [P=0.97] and 1.42 [P=0.02], respectively). On subset analysis, there was no difference in CSS with the addition of brachytherapy for UPSC (P=0.37), CC (P=0.27), or HGE cancer patients (P=0.42). Patients treated with brachytherapy in addition to EBRT did not demonstrate a reduced adjusted risk of EC death compared with EBRT alone (P=0.38). CONCLUSIONS: The addition of brachytherapy to adjuvant EBRT in stages I-II UPSC, CC, and HGE cancer did not demonstrate superior CSS. Thus, patients may not benefit from the addition of brachytherapy to EBRT.

Excellent Long-term Breast Preservation Rate After Accelerated Partial Breast Irradiation Using a Balloon Device.

BACKGROUND: Accelerated partial breast irradiation (APBI) using a balloon device has been well tolerated. A recent retrospective population-based study showed an increase in the rate of subsequent mastectomy for patients who undergo APBI compared with whole breast radiation therapy. Our aim was to analyze the long-term results of patients treated with APBI at our institution to determine the salvage mastectomy and locoregional recurrence rates and cosmesis outcomes. MATERIALS AND METHODS: After institutional review board approval, we conducted a retrospective review of 111 patients treated from June 2003 to October 2014 at our institution for early-stage breast cancer using a balloon device. After lumpectomy and nodal staging, the patients underwent APBI with high-dose rate iridium-192 brachytherapy. A computed tomography-based 3-dimensional plan was created, and a dose of 34 Gy in 10 fractions was given twice daily, 6 hours apart, over 5 days. Follow-up examinations were performed 2 to 3 times annually by either a surgeon and/or a radiation oncologist. Annual mammograms were obtained. The patients included postmenopausal women with node-negative early-stage invasive ductal carcinoma with a tumor size < 3 cm (n = 93) or ductal carcinoma in situ (n = 18). Cosmesis was evaluated using the Harvard criteria, as excellent, good, fair, or poor. RESULTS: At a median follow-up period of 66 months (range, 1-139 months) after completing treatment, with a minimum of 5 years of follow-up data for 62 patients (55.9%), the incidence of ipsilateral breast tumor recurrence (IBTR) was 2.7% (n = 3) and the incidence of ipsilateral axilla nodal recurrence was 1.8% (n = 2). The ipsilateral breast preservation rate was 97.3%. The salvage mastectomy rate was 2.7% (n = 3), and the 5-year salvage mastectomy-free rate was 98.7% (95% confidence interval, 91.0%-99.8%). No distant failure developed, and no breast cancer-related deaths occurred. The 5-year overall survival rate was 91.7% (95% confidence interval, 83.2%-96.0%), and the 10-year breast cancer-specific survival rate was 100%. Of the 3 cases of IBTR, 2 were estrogen receptor negative (P = .076). The mean interval to IBTR was 78.7 ± 27.5 months from treatment completion. A significant association was noted between African-American ethnicity and IBTR (P = .0398). Excellent to good cosmesis was observed in 98.1% of the patients. The maximum skin dose (mean value) for patients with excellent, good, and fair cosmesis was 302.2 Gy, 315.4 Gy, and 372.5 Gy (88.9%, 92.7%, and 109.5% of the prescription dose), respectively. The maximum skin dose was < 340 Gy (100% of the prescribed dose) in 69.9% of patients with excellent to good cosmesis. CONCLUSION: The long-term follow-up data of patients receiving APBI with a balloon device showed a low salvage mastectomy rate with durable long-term breast preservation. Excellent local control with good cosmesis was noted in these postmenopausal patients treated with APBI.

Surgical Technique and Clinically Relevant Resection Cavity Dynamics Following Implantation of Cesium-131 (Cs-131) Brachytherapy in Patients With Brain Metastases.

BACKGROUND: Cesium-131 (Cs-131) brachytherapy is used to reduce local recurrence of resected brain metastases. In order to ensure dose homogeneity and reduce risk of radiation necrosis, inter-seed distance and cavity volume must remain stable during delivery. OBJECTIVE: To investigate the efficacy of the "seeds-on-a-string" technique with intracavitary fibrin glue in achieving cavity volume stability. METHODS: We placed intra-operative Cs-131 brachytherapy in 30 cavities post-resection of brain metastases. Seeds-on-a-string were placed like barrel staves within the cavity with fibrin glue. Serial MRI imaging occurred post-operatively. Pre-operative tumor volumes were compared with post-operative cavity volumes to evaluate volume stability. Thirty patients who underwent post-resective stereotactic radiosurgery (SRS) were used as a control group for volumetric comparison. RESULTS: Cs-131 and SRS patients exhibited consistent cavity shrinkage over the median 110-day follow-up (p<.001), with total median shrinkage of 56.5% (Cs-131) and 84.8% (SRS). During the first month when ~88% of Cs-131 dosage is delivered, however, there was non-significant volume decrease in the Cs-131 group (median 22.0%; p=.063), while SRS patients showed significantly more shrinkage (46.7%; p=.042). No events of radiation necrosis occurred in either group. CONCLUSION: Cs-131 patients exhibited significantly less cavity shrinkage than SRS patients during the first critical month with 88% Cs-131 dose delivery. This significant difference in shrinkage suggests that the intracavitary seeds-on-a-string technique facilitates increased cavity stability, promoting more homogenous dose delivery.

Current and emerging roles of functional imaging in radiation therapy.

The advent of functional imaging facilitates the acquisition of patient-specific tumor characteristics, including its metabolic state and regional oxygen tension. Recent advances promote incorporating this information with data obtained from current imaging techniques, such as MRI and CT, to manage various malignancies. Functional imaging's vital roles progressively evolved to include: aiding in diagnosis, improving radiation treatment planning, differentiating tumor volume from surrounding normal tissues which enables dose escalation to the former while improving sparing of the latter, adapting radiation therapy regimens according to a tumor's response to initial treatment, and assessing radiation therapy response and toxicity. This review explores functional imaging in radiation oncology in the context of these five applications, as well as its comparison to, and integration with, existing imaging modalities. In parallel with advances in functional imaging and understanding of tumor microbiology, the emergence of diverse tracers provides a plethora of options to distinguish and manage malignancies on the basis of specific metabolic processes and changing microenvironmental cues. Current limitations, potential concerns, and future innovations of functional imaging are also discussed.

Second cancer, breast cancer, and cardiac mortality in stage T1aN0 breast cancer patients with or without external beam radiation therapy: a national registry study.

INTRODUCTION/BACKGROUND: With improved BC screening and treatment, the risk for long-term toxicities of treatments must be considered, especially in good prognosis patients. In this study we examined the outcome, risks of second cancers, and cardiac mortality with RT for early-stage BC from recent years. MATERIALS AND METHODS: Analysis of the SEER database was conducted for women who had stage T1aN0 BC as their first primary malignancy between 1990 and 1997 and were treated with partial or complete mastectomy with or without external beam RT. The overall survival (OS), BC-specific survival (BCSS), cardiac cause-specific survival (CCS), and deaths from second cancers in the chest area were compared between the RT and no-RT groups. RESULTS: Of the 6515 women identified, 2796 received RT and 3719 did not. The median age group (60-64 years) and follow-up lengths (approximately 15 years) were similar. Compared with the RT group, the no-RT group was associated with lower 10-year OS (85.5% vs. 79.3%; P < .0001), BCSS (97.3% vs. 96.4%; P = .04), and CCS (97.0% vs. 93.8%; P < .0001). In the RT group, left-sided BC was not associated with higher cardiac mortality. There were no statistically significant incidences in mortality due to subsequent cancers. The most common second cancer mortality included 114 (2%) lung, 25 (0.4%) lymphoma, 19 (0.3%) leukemia, 3 (0.05%) soft tissue, and 2 (0.03%) esophagus. CONCLUSION: This review of SEER data suggests that secondary malignancy in the chest area and cardiac mortality are rare after RT in the 1990s for T1aN0 BC.

Equivalent Survival With Mastectomy or Breast-conserving Surgery Plus Radiation in Young Women Aged < 40 Years With Early-Stage Breast Cancer: A National Registry-based Stage-by-Stage Comparison.

BACKGROUND: Studies have shown that young patients with early-stage breast cancer (BC) are increasingly undergoing mastectomy instead of breast-conserving therapy (BCT) consisting of lumpectomy and radiation. We examined the difference in outcomes in young women (aged < 40 years) who had undergone BCT versus mastectomy. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results database was queried for women aged < 40 years with stage I or II invasive BC treated with surgery from 1998 to 2003. Breast cancer-specific survival (BCSS) and overall survival (OS) were evaluated using Kaplan-Meier survival analysis and the log-rank test between treatment types. RESULTS: Of the 7665 women, 3249 received BCT and 2627 underwent mastectomy without radiation. When separated by stage (I, IIA, and IIB), with a median follow-up duration of 111 months, the BCT and mastectomy-only groups showed no statistically significant differences in BCSS and OS. Overall, the age group of 35 to 39 years (66% of total) was associated with better 10-year BCSS (88%) and OS (86.1%) compared with the younger patients aged 20 to 34 years (34% of total). The latter group had a 10-year BCSS and OS of 84.1% and 82.3%, respectively (P < .001 for both BCSS and OS). However, when the patients of each age group were further subdivided by stage, the BCT group continued to show noninferior BCSS and OS compared with the mastectomy group in all subgroups. CONCLUSION: The results of our study suggest that although young age might be a poor prognostic factor for BC, no evidence has shown that these patients will have better outcomes after mastectomy than after BCT.