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BACKGROUND Despite international practice guidelines endorsing radiotherapy (RT) as the preferred initial therapy, treatment approaches vary for patients with early-stage follicular lymphoma. The authors engaged the National Cancer Data Base to analyze patterns of care and survival outcomes for patients with early-stage follicular lymphoma in the era of modern therapy. METHODS A National Cancer Data Base retrospective cohort study was conducted of 35,961 patients with lymph node and extranodal, American Joint Committee on Cancer stage I to II, WHO grade 1 to 2 follicular lymphoma who were diagnosed between 1998 and 2012. Univariate and multivariable analyses were performed to identify sociodemographic, treatment, and tumor characteristics that were predictive of overall survival (OS) and treatment use. Propensity score-adjusted Cox proportional hazards ratios for survival in patients treated for follicular lymphoma were used. RESULTS Of the 35,961 patients with follicular lymphoma included in the current study, 63% had stage I disease, 79% were without extranodal disease, and 61% were aged >60 years. RT use decreased from 37% in 1999 to 24% in 2012 ( P<.0001), with corresponding significant increases in observation and single-agent chemotherapy. Patients who received RT had 5-year and 10-year OS rates of 86% and 68%, respectively, compared with 74% and 54%, respectively, for those who did not receive RT ( P<.0001). On multivariable survival analysis, including a propensity score to account for potential uncaptured confounding variables due to a lack of randomization, upfront RT remained independently associated with improved OS (hazard ratio of death, 0.54; 95% confidence interval, 0.47-0.63 [ P<.0001]). CONCLUSIONS RT is an increasingly underused treatment approach in the era of modern therapy for patients with early-stage follicular lymphoma. The use of RT appears to improve OS and should remain standard practice as encouraged by clinical practice guidelines. Cancer 2015;121:3325-3334. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this consensus statement from the American Brachytherapy Society (ABS) is to summarize recent advances and to generate general guidelines for the management of medically inoperable endometrial cancer patients with radiation therapy. Methods Recent advances in the literature were summarized and reviewed by a panel of experts. Panel members participated in a series of conference calls and were surveyed to determine their current practices and patterns. This document was reviewed and approved by the full panel, the ABS Board of Directors and the ACR Commission on Radiation Oncology. Results A transition from two-dimensional (2D) to three-dimensional (3D) treatment planning for the definitive treatment of medically inoperable endometrial cancer is described. Magnetic resonance (MR) imaging can be used to define the gross tumor volume (GTV), clinical target volume (CTV), and the organs at risk (OARs). Brachytherapy alone can be used for medically inoperable endometrial cancer patients with clinical Stage I cancer with no lymph node involvement and no evidence of deep invasion of the myometrium on MR imaging. In the absence of MR imaging, a combined approach using external beam and brachytherapy may be considered. Conclusions Recent advances support the use of MR imaging and 3D planning for brachytherapy treatment for medically inoperable endometrial cancer. [ABSTRACT FROM AUTHOR]

Purpose: To examine clinical outcomes and relapse patterns in locally advanced vulvar carcinoma treated using preoperative chemotherapy and intensity modulated radiation therapy (IMRT). Methods and Materials: Forty-two patients with stage I-IVA (stage I, n=3; stage II, n=13; stage III, n=23; stage IVA, n=3) vulvar cancer were treated with chemotherapy and IMRT via a modified Gynecological Oncology Group schema using 5-fluorouracil and cisplatin with twice-daily IMRT during the first and last weeks of treatment or weekly cisplatin with daily radiation therapy. Median dose of radiation was 46.4 Gy. Results: Thirty-three patients (78.6%) had surgery for resection of vulva; 13 of these patients also had inguinal lymph node dissection. Complete pathologic response was seen in 48.5% (n=16) of these patients. Of these, 15 had no recurrence at a median time of 26.5 months. Of the 17 patients with partial pathological response, 8 (47.1%) developed recurrence in the vulvar surgical site within a median of 8 (range, 5-34) months. No patient had grade ≥3 chronic gastrointestinal/genitourinary toxicity. Of those having surgery, 8 (24.2%) developed wound infections requiring debridement. Conclusions: Preoperative chemotherapy/IMRT was well tolerated, with good pathologic response and clinical outcome. The most common pattern of recurrence was local in patients with partial response, and strategies to increase pathologic response rate with increasing dose or adding different chemotherapy need to be explored to help further improve outcomes. [Copyright &y& Elsevier]

Abstract: Purpose: The purpose of this study was to determine the patterns of failure in patients diagnosed with cervical cancer treated with definitive radiotherapy and who subsequently had complete metabolic response (CMR) seen on early post-therapy (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging. Additionally, we sought to determine what factors predict disease recurrence in this patient population. Methods and materials: We reviewed the records of 155 patients diagnosed with cervical cancer from stages IB1 to IVA who were treated with definitive chemoradiation therapy between 2003 and 2011 and had a FDG-PET at 10–16weeks following completion of therapy. One hundred and twelve (72.0%) had CMR on follow-up FDG-PET and comprised the patients in this study. Results: The median age of patients with CMR was 51years and the median tumor size 4.9cm. Median follow up was 15months. Of the 112 patients, 11 (9.8%) had a recurrence and six (5.4%) had isolated local recurrences, and five (4.5%) had distant recurrence. Median time to recurrence was 9months. Three-year actuarial disease-free survival and overall survival rates were 78.9% and 88.0% respectively. On Cox regression multivariate analysis, tumor size was predictive of increased risk of local recurrence in these patients with CMR with p <0.025. Age, stage, histology and nodal positivity were not significant for predicting local, distant or any recurrence. Conclusion: Patients treated with concurrent chemoradiation had a CMR which demonstrated good clinical outcomes in terms of local control. There were equal numbers of patients suffering local and distant recurrences. In patients with a CMR, only tumor size was an independent predictor for local recurrence. [Copyright &y& Elsevier]

Abstract: Purpose: To determine the optimal margin needed around the femoral vessels for appropriate inguinofemoral lymph node coverage and to propose guidelines defined by anatomic boundaries for clinical target volume delineation. Methods and Materials: Twenty-two patients with pelvic malignancies and involved inguinal lymph nodes treated with conformal radiation therapy were selected. Lymph nodes were considered positive if they were pathologically malignant by biopsy, had 18F-fluorodeoxyglucose avidity on positron emission tomography or measured ≥1.5 cm on computed tomographic scan. We measured distance from the center of node(s) to the edge of the nearest femoral vessel. Results: There were 52 total positive inguinal nodes among 22 patients. Relative to the femoral vessels, the location of the nodes were 51.9% anteromedial, 21.2% anterior, 11.5% anterolateral, 9.6% medial, 1.9% posterior, and 3.9% lateral. To cover ≥90% disease, the margins needed around the nearest femoral vessel were anteromedial ≥35 mm, anterior ≥23 mm, anterolateral ≥25 mm, medial ≥22 mm, posterior ≥9 mm, and ≥32 mm lateral. The corresponding anatomic boundaries were the following: laterally, medial border of the iliopsoas; medially, lateral border of adductor longus or medial end of pectineus; posteriorly, iliopsoas muscle laterally and anterior aspect of the pectineus muscle; medially and anteriorly, the anterior edge of the sartorius muscle. Most of the macroscopic nodes were medial or anteromedial to the femoral vessels. No patient had involved posterior or lateral nodes alone without positive nodes in the anterior or anteromedial positions. Conclusions: Circumferential margins around femoral vessels required to adequately cover this nodal region were >2 cm in most directions. Contouring the inguinal lymph nodes as a compartment defined by the anatomic landmarks suggested above may be more reproducible. Physicians should exercise caution in extrapolating pelvic nodal contouring guidelines to inguinal lymph nodal contouring. [Copyright &y& Elsevier]

Abstract: Purpose: There is limited published data on high-dose-rate interstitial brachytherapy (HDRBT) for cervical cancer resulting in no consensus on a fractionation schedule. This study reports our experience of CT-based HDRBT for treating locally advanced cervical cancer. Methods and Materials: Forty-seven patients diagnosed with Stage IIB–IVA cervical cancer not suitable for intracavitary brachytherapy were treated with HDRBT from March 2005 to November 2010. All patients received external beam radiation therapy with a median dose of 45Gy and all had one interstitial implantation followed by 3.75–5Gy×5 fractions in a twice daily (BID) schedule. Total doses for clinical target volume and organs at risk, including rectum, bladder, and sigmoid, were summated and normalized to a biologically equivalent dose of 2Gy per fraction. At 3 months posttherapy, early response was assessed with clinical examination and positron emission tomography (PET/CT) imaging. Results: Median clinical target volume D 90 (dose delivered to 90% of the clinical target volume) was 76.3 (59.0–86.9) Gy and the 2cc dose to the bladder, rectum, and sigmoid colon organs were 70.2 (55.9–77.7), 65.8 (54.9–80.6), and 56.5 (45.0–71.2) Gy, respectively. Posttreatment, 12 patients had evidence of persistent disease on PET/CT. Eleven of the 35 patients who had complete response developed recurrences. Two patients developed late Radiation Therapy Oncology Group ≥3 rectal toxicities. Two-year actuarial local control, disease-free survival, overall survival, and Grade ≥3 toxicities were 61%, 43%, 59%, and 10%, respectively. Conclusion: Our approach of a single implantation procedure followed by five fractions of HDRBT was well tolerated with early results demonstrating a moderate response and local control rate with acceptable toxicities. [Copyright &y& Elsevier]

Purpose: Clinical pathways are an important tool used to manage the quality in health care by standardizing processes. This study evaluated the impact of the implementation of a peer-reviewed clinical pathway in a large, integrated National Cancer Institute–Designated Comprehensive Cancer Center Network. Methods: In 2003, we implemented a clinical pathway for the management of bone metastases with palliative radiation therapy. In 2009, we required the entry of management decisions into an online tool that records pathway choices. The pathway specified 1 or 5 fractions for symptomatic bone metastases with the option of 10–14 fractions for certain clinical situations. The data were obtained from 13 integrated sites (3 central academic, 10 community locations) from 2003 through 2010. Results: In this study, 7905 sites were treated with 64% of courses delivered in community practice and 36% in academic locations. Academic practices were more likely than community practices to treat with 1–5 fractions (63% vs. 23%; p < 0.0001). The number of delivered fractions decreased gradually from 2003 to 2010 for both academic and community practices (p < 0.0001); however, greater numbers of fractions were selected more often in community practices (p < 0.0001). Using multivariate logistic regression, we found that a significantly greater selection of 1–5 fractions developed after implementation online pathway monitoring (2009) with an odds ratio of 1.2 (confidence interval, 1.1–1.4) for community and 1.3 (confidence interval, 1.1–1.6) for academic practices. The mean number of fractions also decreased after online peer review from 6.3 to 6.0 for academic (p = 0.07) and 9.4 to 9.0 for community practices (p < 0.0001). Conclusion: This is one of the first studies to examine the efficacy of a clinical pathway for radiation oncology in an integrated cancer network. Clinical pathway implementation appears to be effective in changing patterns of care, particularly with online clinical peer review as a valuable aid to encourage adherence to evidence-based practice. [Copyright &y& Elsevier]

Abstract: Purpose: This report presents an update to the American Brachytherapy Society (ABS) high-dose-rate (HDR) brachytherapy guidelines for locally advanced cervical cancer. Methods: Members of the ABS with expertise in cervical cancer formulated updated guidelines for HDR brachytherapy using tandem and ring, ovoids, cylinder, or interstitial applicators for locally advanced cervical cancer. These guidelines were written based on medical evidence in the literature and input of clinical experts in gynecologic brachytherapy. Results: The ABS affirms the essential curative role of tandem-based brachytherapy in the management of locally advanced cervical cancer. Proper applicator selection, insertion, and imaging are fundamental aspects of the procedure. Three-dimensional imaging with magnetic resonance or computed tomography or radiographic imaging may be used for treatment planning. Dosimetry must be performed after each insertion before treatment delivery. Applicator placement, dose specification, and dose fractionation must be documented, quality assurance measures must be performed, and followup information must be obtained. A variety of dose/fractionation schedules and methods for integrating brachytherapy with external-beam radiation exist. The recommended tumor dose in 2-Gray (Gy) per fraction radiobiologic equivalence (normalized therapy dose) is 80–90Gy, depending on tumor size at the time of brachytherapy. Dose limits for normal tissues are discussed. Conclusion: These guidelines update those of 2000 and provide a comprehensive description of HDR cervical cancer brachytherapy in 2011. [Copyright &y& Elsevier]

Abstract: Purpose: To provide longitudinal follow-up and assess the intermediate outcomes in breast cancer patients treated with the MammoSite® radiation therapy system. Methods and Material: Ninety-two patients with histologically proven stage 0-II breast cancer were treated with MammoSite® accelerated partial breast irradiation after breast-conserving surgery. The catheter was placed at the time of surgery or postoperatively. Treatment prescription was 3.4Gy b.i.d. for a period of five days using high-dose-rate afterloading. Clinical and dosimetric parameters including dose to 90% of PTV, volume of PTV receiving 100% of dose, volume of PTV receiving 150% of dose, edited PTV, and dose homogeneity index were analyzed as variables correlating with late effects. Results: All patients received the prescribed treatment. Seventy-seven percent of patients had intraoperative catheter placement, which was associated with a higher rate of persistent seroma (79%). The presence of seroma did not affect cosmesis. Ten patients developed telangiectasia at a median of 20.5 months. Skin dose and balloon-to-skin distance had a significant correlation with the development of telangiectasia that significantly affected cosmetic grading. The telangiectasia incidence for maximum skin dose of >100% and >125% of the prescription dose were 28% and 63%, compared with 0% (p =0.0001) and 4.2% (p =0.0001) for doses of ≤100% and ≤125%, respectively. Overall, most patients had excellent cosmetic results, and local control of disease was excellent. Conclusions: MammoSite® radiation therapy system demonstrates excellent local control and cosmetic outcome with extended followup. The maximum skin dose should be kept below 100% to reduce late effects on skin and improve cosmetic outcome. The persistence of seroma is higher with intraoperative placement of the catheter, and therefore postoperative placement is preferred. [Copyright &y& Elsevier]

Abstract: Purpose: The purpose of this study was to determine whether the ClearPath (CP) multicatheter hybrid device was able to achieve acceptable dosimetry in patients in whom the proximity of the breast surgical cavity to the skin precluded treatment with intracavitary MammoSite (MS) brachytherapy. Methods and materials: The study consisted of 11 patients who had the MS catheter placed and who were subsequently not treated due to inadequate skin distance. A phantom scan of the CP multicatheter hybrid device was superimposed on the MS CT scan and a dosimetric comparison was performed. Results: The median MS balloon size, diameter, and minimum skin distance were 40cc, 4.1cm, and 5mm, respectively. The D 90, V 100, V 150, and V 200 with MS vs. CP were 95.29% vs. 97.06%, 88.8% vs. 91.3%, 35.7% vs. 38.0%, and 9.4% vs. 9.6%, respectively. The median maximum skin dose was 5.5Gy vs. 3.9Gy (p <.0001). The median dose homogeneity index (DHI) was 0.60 vs. 0.59 (p =.09). The median maximum rib, heart, and lung dose were 2.17Gy vs. 2.18Gy, 2.17Gy vs. 2.18Gy, and 0.50Gy vs. 0.56Gy, respectively. Conclusion: The hybrid CP catheter reduced the skin dose significantly without compromising the planning target volume coverage, DHI, or dose to other critical organs. The use of this device has the potential to increase the applicability of accelerated partial breast brachytherapy (APBI) in patients with a surgical cavity close to skin compared with balloon brachytherapy. [Copyright &y& Elsevier]

Purpose: To determine the dosimetric and toxicity differences between prone and supine position intensity-modulate radiotherapy in endometrial cancer patients treated with adjuvant radiotherapy. Methods: Forty-seven consecutive endometrial cancer patients treated with adjuvant RT were analyzed. Of these, 21 were treated in prone position and 26 in the supine position. Dose–volume histograms for normal tissue structures and targets were compared between the two groups. Acute and chronic toxicity were also compared between the cohorts. Results: The percentage of volume receiving 10, 20, 30, 40, 45, and 50 Gy for small bowel was 89.5%, 69%, 33%, 12.2%, 5%, and 0% in the prone group and 87.5%, 62.7%, 26.4%, 8%, 4.3%, and 0% in the supine group, respectively. The difference was not statistically significant. The dose–volume histograms for bladder and rectum were also comparable, except for a slightly greater percentage of volume receiving 10 Gy (1.5%) and 20 Gy (5%) for the rectum in the prone group. Acute small bowel toxicities were Grade 1 in 7 patients and Grade 2 in 14 patients in the prone group vs. Grade 1 in 6 patients and Grade 2 in 19 patients in the supine group. Chronic toxicity was Grade 1 in 7 patients and Grade 3 in 1 patient in the prone group and Grade 1 in 5 patients in the supine group. Conclusion: These preliminary results suggest that no difference exists in the dose to the normal tissue and toxicity between prone and supine intensity-modulated radiotherapy for endometrial cancer. Longer follow-up and more outcome studies are needed to determine whether any differences exist between the two approaches. [Copyright &y& Elsevier]

Abstract: Purpose: The study aimed to assess the outcome of locally advanced cervical and vaginal cancer treated with high-dose-rate interstitial brachytherapy (HDRB). Methods and materials: Between 1998 and 2004, 16 previously unirradiated patients with locally advanced cervical and vaginal cancer not suitable for intracavitary brachytherapy because of distorted anatomy or extensive vaginal disease were treated with HDRB in combination with external beam radiotherapy. All patients received whole pelvis external beam radiation therapy (EBRT) followed by interstitial implantation. The median whole pelvis external beam dose was 45Gy (range, 39.6–50.4Gy) with 11 patients receiving parametrial boost to a median dose of 9Gy. Twelve (75%) of these patients received chemotherapy concurrent with external beam. All patients received a single HDRB procedure using a modified Syed–Neblett template. A CT scan was performed postimplant for needle placement verification and treatment planning purpose. Dose was prescribed to the tumor volume based on the radiographic and clinical examination. All patients received 18.75Gy in five fractions delivered twice daily. The median followup was 25 months (6–69 months). Results: Median cumulative biologic effective dose (EBRT+HDRB) to tumor volume was 78.9Gy10 with the range of 72.5–85.2Gy10. Median cumulative biologic effective dose for the rectum and bladder were 99.4Gy3 (range, 79.6–107.8Gy3) and 96.4Gy3 (range, 78.3–105.3Gy3), respectively. Complete response was achieved in 13 (81%) patients with 3 patients having persistent disease. Five of these 13 patients developed recurrence at a median time of 14 months (distant in 4 and local and distant in 1). The 5-year actuarial local control and cause-specific survival were 75% and 64%, respectively. In subset analysis, 5-year actuarial local control was 63% for cervical cancer patients and 100% for vaginal cancer patients. No patient had acute Grade 3 or 4 morbidity. Grade 3 or 4 delayed morbidity resulting from treatment occurred in 1 patient with 5-year actuarial rate of 7%. Three patients had late Grade 2 rectal morbidity and 1 patient had Grade 2 small bowel morbidity. Conclusions: Our series suggests that single interstitial implantation procedure with five fractions of 3.75Gy each to target volume is an effective and safe fractionation schedule. The integration of imaging modality helps in decreasing dose to the critical organs. Additional patients and followup are ongoing to determine the long-term efficacy of this approach. [Copyright &y& Elsevier]

Background: Clinical pathways outline criteria for dose homogeneity and critical organ dosimetry. Based upon an internal audit showing suboptimal compliance with dosimetric parameters in whole breast irradiation (WBI), we conducted a mandatory web-based teaching conference for the network. This study reports the impact of this initiative on subsequent treatment plans.Methods: Radiation treatment plans were collected for the 10 most recent patients receiving WBI at 16 institutions within the UPMC Hillman Cancer Center network. Subsequently, a web-based conference was conducted to educate staff physicians, physicists, and dosimetrists with goals for dose homogeneity and critical organ dosimetry. Six months post-conference, another 10 plans were collected from each site and compared to pre-conference plans for deviations from dosimetric criteria.Results: Dose homogeneity significantly improved after the conference with breast V105% decreasing from 15.6% to 11.2% (p = 0.004) and breast V110% decreasing from 1.3% to 0.04% (p = 0.008). A higher percentage of cases were compliant with dosimetric criteria, with breast V105% > 20% decreasing from 22.5% to 7.5% of cases (p = 0.0002) and breast V110% > 0% decreasing from 13.8% to 4.4% of cases (p = 0.003).Conclusions: Implementation of a web-based teaching conference helped improve adherence to clinical pathway dosimetric guidelines for WBI. In radiation oncology networks, this may be an effective model to ensure quality in routine practice and can be extrapolated to other disease sites. [ABSTRACT FROM AUTHOR]

Purpose: To conduct a cost-effectiveness analysis to determine whether stereotactic body radiation therapy (SBRT) is a cost-effective therapy compared with radiofrequency ablation (RFA) for patients with unresectable colorectal cancer (CRC) liver metastases.Methods and Materials: A cost-effectiveness analysis was conducted using a Markov model and 1-month cycle over a lifetime horizon. Transition probabilities, quality of life utilities, and costs associated with SBRT and RFA were captured in the model on the basis of a comprehensive literature review and Medicare reimbursements in 2014. Strategies were compared using the incremental cost-effectiveness ratio, with effectiveness measured in quality-adjusted life years (QALYs). To account for model uncertainty, 1-way and probabilistic sensitivity analyses were performed. Strategies were evaluated with a willingness-to-pay threshold of $100,000 per QALY gained.Results: In base case analysis, treatment costs for 3 fractions of SBRT and 1 RFA procedure were $13,000 and $4397, respectively. Median survival was assumed the same for both strategies (25 months). The SBRT costs $8202 more than RFA while gaining 0.05 QALYs, resulting in an incremental cost-effectiveness ratio of $164,660 per QALY gained. In 1-way sensitivity analyses, results were most sensitive to variation of median survival from both treatments. Stereotactic body radiation therapy was economically reasonable if better survival was presumed (>1 month gain) or if used for large tumors (>4 cm).Conclusions: If equal survival is assumed, SBRT is not cost-effective compared with RFA for inoperable colorectal liver metastases. However, if better local control leads to small survival gains with SBRT, this strategy becomes cost-effective. Ideally, these results should be confirmed with prospective comparative data. [ABSTRACT FROM AUTHOR]

Purpose Multichannel vaginal cylinder brachytherapy (MCVCB) has the potential to sculpt dose distribution, although this is typically reserved for lesions <5-mm thick. The aim of this study was to investigate the dosimetric consequences of treating lesions with MCVCB of varying locations, ≥5 mm in thickness. Methods and Materials Patients previously treated with MCVCB were randomly selected to each fill one of six categories based on location (lateral, anterior, or vaginal cuff and/or apex) and size of cylinder (2.5 or 3.0 cm). Based on magnetic resonance image, each patient's target lesion was extended circumferentially into theoretical high-risk clinical target volumes measuring 5, 7, and 10 mm in thickness. Image-based brachytherapy treatment plans for each of the six patients' three target volumes were generated. Total 2 Gy per fraction equivalent dosages (EQD2) were calculated using an external beam radiation therapy dose of 45 Gy in 25 fractions in conjunction with a high-dose-rate brachytherapy dose of 25 Gy in five fractions. Results Maximum EQD2 vaginal surface doses in gray for 5-, 7-, and 10-mm targets were as follows (location-cylinder size): lateral-3.0 cm: 122/153/210, lateral-2.5 cm: 145/195/301, anterior-3.0 cm: 115/135/197, anterior-2.5 cm: 132/173/283, apex-3.0 cm: 173/241/367, and apex-2.5 cm: 349/461/706. Total rectal EQD2 D 2 cc ranged from 53.9 to 67.2 Gy. Total bladder EQD2 D 2 cc ranged from 51.5 to 71.2 Gy. Conclusions The vaginal surface dose seems to be the dose-limiting structure for anterior, lateral, and apical vaginal lesions. Caution should be taken when treating lesions >5 mm in depth, with particular attention to vaginal surface dose, especially for apical lesions and with smaller cylinders. In such cases, interstitial brachytherapy should be given strong consideration. [ABSTRACT FROM AUTHOR]

Purpose: Intensity modulated radiation therapy is used to reduce dose to adjacent critical structures while maintaining adequate target coverage, but it requires precise target localization. We report the 3-dimensional distribution of para-aortic (PA) lymph nodes (LN) in pelvic malignancies. We propose a guideline to accurately define the PA LN by anatomic landmarks and compare our data with published guidelines for pancreatic cancer. Methods and Materials: A retrospective analysis was performed on 46 patients with pelvic malignancies and positive PA LNs. Positive LNs were defined based on size and morphology or fluorodeoxyglucose avidity. All PA LNs were characterized into 3 groups based on location: left PA (between aorta and left psoas muscle), aortocaval (between aorta and inferior vena cava), and right paracaval (between inferior vena cava and right psoas muscle). Patients with retrocrural LNs were also analyzed. Results: One hundred thirty-three positive PA LNs were evaluated. The majority of the PA LNs were in the left PA (59%) and aortocaval (35) regions, and only 8% were in the right paracaval region. All patients with positive right paracaval LNs also had involved left PA LNs, with only 1 exception. The highest PA LN involvement was at the level of the renal vessels and was seen in 28% of patients. Of these patients with disease extending to renal vessels, 38% had retrocrural LN involvement. Conclusions: The nodal contouring for the PA region should not be defined by a fixed circumferential margin around the vessels. The left PA and aortocaval spaces should be covered adequately because these are common locations of PA LNs. For microscopic disease superiorly, contouring should extend up to renal vessels rather than a fixed bony landmark. For patients who have nodal involvement at renal vessels, one can consider including retrocrural LNs. Radiation Therapy Oncology Group Para-aortic Contouring Guidelines for Pancreatic Neoplasm are not applicable to gynecological malignancies. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Radiation can be delivered via four-field box (BOX-RT) or intensity modulated radiation therapy (IMRT). We sought to evaluate the cost-effectiveness (C/E) of IMRT relative to BOX-RT for the treatment of locally advanced cervical cancer. Methods: A three-year Markov model with eight-week cycles was developed to compare IMRT to BOX-RT. A proportion (25%) received extended-field radiation therapy (EFRT) to include para-aortic nodes. The model assumed equal overall survival (OS). The model captured costs and utility estimates for BOX-RT, IMRT, and each complication. Modeled complications included acute and chronic toxicities. Baseline model assumptions were obtained by literature review and supplemented by expert opinion. Costs were based on Medicare reimbursement rates and the Agency for Healthcare Research and Quality Database. Treatment strategies were compared using an incremental cost-effectiveness ratio (ICER). One-way, probabilistic and structural sensitivity analyses were performed to account for uncertainty in assumptions. The C/E of each strategy was evaluated from the perspective of the health care system. Results: C/E analysis revealed an ICER for IMRT of $182,777/quality adjusted life year (QALY) gained. Although this value was higher than the willingness to pay threshold of $100,000/QALY, sensitivity analysis revealed several modifications that would make IMRT a C/E option relative to BOX-RT. For patients requiring EFRT, IMRT was C/E with an ICER of $91,580/QALY. Conclusions: Although IMRT was not C/E at the $100,000 willingness-to-pay threshold, in those requiring EFRT, IMRT was C/E relative to BOX-RT. A randomized trial comparing IMRT to BOX-RT for the treatment of locally advanced cervical cancer is warranted. [Copyright &y& Elsevier]

Purpose: Katz suggested a nomogram for predicting having four or more positive nodes in sentinel lymph node (SLN)-positive breast cancer patients. The findings from this formula might influence adjuvant radiotherapy decisions. Our goal was to validate the accuracy of the Katz nomogram. Methods and Materials: We reviewed the records of 309 patients with breast cancer who had undergone completion axillary lymph node dissection. The factors associated with the likelihood of having four or more positive axillary nodes were evaluated in patients with one to three positive SLNs. The nomogram developed by Katz was applied to our data set. The area under the curve of the corresponding receiver operating characteristics curve was calculated for the nomogram. Results: Of the 309 patients, 80 (25.9%) had four or more positive axillary lymph nodes. On multivariate analysis, the number of positive SLNs (p < .0001), overall metastasis size (p = .019), primary tumor size (p = .0001), and extracapsular extension (p = .01) were significant factors predicting for four or more positive nodes. For patients with <5% probability, 90.3% had fewer than four positive nodes and 9.7% had four or more positive nodes. The negative predictive value was 91.7%, and sensitivity was 80%. The nomogram was accurate and discriminating (area under the curve, .801). Conclusion: The probability of four or more involved nodes is significantly greater in patients who have an increased number of positive SLNs, increased overall metastasis size, increased tumor size, and extracapsular extension. The Katz nomogram was validated in our patients. This nomogram will be helpful to clinicians making adjuvant treatment recommendations to their patients. [Copyright &y& Elsevier]

Background The primary treatment of early stage cervical carcinoma (IB-IIA) is either surgery or radiation therapy based on the pivotal Milan randomized study published twenty years ago. In the presence of high-risk features, the gold standard treatment is concurrent chemotherapy and radiation therapy (CRT) whether it is the in the postoperative or the definitive setting. Using the National Cancer Data Base (NCDB), the goal of our study is to compare the outcomes of surgery and radiation therapy in the chemotherapy era. Methods Between 2004 and 2013, 5478 patients diagnosed with early stage cervical cancer were divided into 2 groups based on their primary treatment: non-surgical ( n = 1980) and surgical groups ( n = 3498). The distribution of patient/tumor characteristics and treatment variables with their relation to overall survival and proportional regression models were assessed to investigate the superiority of one approach over the other. Propensity score analysis adjusted for imbalance of covariates to create a well-matched-patient cohort. Findings At 46 months median follow-up, the 5-year overall survival was similar between both groups (73·8% vs. 75.7%; p = 0.619) after applying propensity score analysis. On multivariate analysis, high Charlson comorbidity score, stage IIA disease, larger tumor size, positive lymph nodes and high-grade disease were significant predictors of poor outcome while older age and treatment approach were not. Interpretation Our analysis suggests that surgery (followed by adjuvant RT or CRT) and definitive radiotherapy (with or without chemotherapy) result in equivalent survival. Prospective studies are warranted to establish this paradigm in the chemotherapy era. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to develop a radiation therapy (RT) contouring atlas and recommendations for women with postoperative and locally advanced vulvar carcinoma.Methods and Materials: An international committee of 35 expert gynecologic radiation oncologists completed a survey of the treatment of vulvar carcinoma. An initial set of recommendations for contouring was discussed and generated by consensus. Two cases, 1 locally advanced and 1 postoperative, were contoured by 14 physicians. Contours were compared and analyzed using an expectation-maximization algorithm for simultaneous truth and performance level estimation (STAPLE), and a 95% confidence interval contour was developed. The level of agreement among contours was assessed using a kappa statistic. STAPLE contours underwent full committee editing to generate the final atlas consensus contours.Results: Analysis of the 14 contours showed substantial agreement, with kappa statistics of 0.69 and 0.64 for cases 1 and 2, respectively. There was high specificity for both cases (≥99%) and only moderate sensitivity of 71.3% and 64.9% for cases 1 and 2, respectively. Expert review and discussion generated consensus recommendations for contouring target volumes and treatment for postoperative and locally advanced vulvar cancer.Conclusions: These consensus recommendations for contouring and treatment of vulvar cancer identified areas of complexity and controversy. Given the lack of clinical research evidence in vulvar cancer radiation therapy, the committee advocates a conservative and consistent approach using standardized recommendations. [ABSTRACT FROM AUTHOR]

Purpose The National Cancer Data Base (NCDB) was analyzed to evaluate practice patterns and the impact of radiotherapy modalities for endometrial cancer treated with primary radiotherapy. Methods and Materials The NCDB was queried for Stage I endometrioid adenocarcinoma patients treated with primary radiotherapy without surgery from 1998 to 2006. Brachytherapy (BT) utilization factors were established using multivariable logistic regression. Log-rank and Cox proportional hazards modeling were used to assess variables impacting survival. Results A total of 853 patients were analyzed: 23.7%, 31.3%, and 45.0% received BT alone, external beam radiotherapy (EBRT) and BT, or EBRT alone. The BT utilization ranged from 40.5% to 51.9% over time ( p = 0.70). Lower utilization was associated with advanced age (≥80 years: odds ratio [OR] 0.43, 95% confidence interval [CI] 0.28–0.65, p < 0.01) and facilities with volume in the bottom quartile (OR 0.44, 95% CI 0.30–0.66, p < 0.01). Utilization was higher among patients living more than 30 miles from the facilities (OR 2.14, 95% CI 1.35–3.42, p < 0.01). With 36-month median followup, unadjusted median survivals for EBRT dose of 30 Gy or lower, EBRT dose higher than 30 Gy, BT, and EBRT + BT were 12.6, 31.1, 44.6, and 57.1 months ( p < 0.01). After correcting for other factors, higher risk of mortality was seen with EBRT dose of 30 Gy or lower (hazard ratio [HR] 2.75, 95% CI 1.66–4.55, p < 0.01) and EBRT dose higher than 30 Gy (HR 1.43, 95% CI 1.07–1.91, p = 0.02) compared with EBRT + BT. No difference was seen using BT alone (HR 1.29, 95% CI 0.92–1.79, p = 0.14). Conclusion BT utilization for nonsurgically managed endometrial cancer remains low with most patients receiving EBRT alone. Despite concerns of overtreatment in a population with competing causes of death, BT appears to improve survival. [ABSTRACT FROM AUTHOR]

Background and purpose In order to assess tumor regression and outcomes, a volumetric analysis was conducted for cervical cancer patients treated with magnetic resonance imaging (MRI)-based image-guided brachytherapy (IGBT). Materials and methods Consecutive patients with FIGO stage IB1–IVA cervical cancer receiving chemoradiation from 2007 to 2013 were identified, excluding patients with perineal template-based interstitial brachytherapy or without undergoing MRI. A ring and tandem applicator ± interstitial needles was used. T2-weighted imaging was completed following applicator insertion. Gross tumor volumes (GTVs) were retrospectively contoured: initial GTV (GTV Pre-EBRT ), GTV at first brachytherapy (GTV IGBT ) and percent residual GTV at first brachytherapy (% GTV Residual ). Results Eighty-four patients were identified. With 20.8-month median follow-up, two-year estimates of local control (LC), disease-free survival (DFS) and overall survival (OS) were 91.3, 79.8, and 85.0%, respectively. Multivariate Cox regression revealed adenocarcinoma (HR 5.88, p = 0.03) and GTV IGBT (HR 1.17, p < 0.01) as predictors for local failure. GTV IGBT > 7.5 cc was associated with inferior 2-year LC (75.0 vs. 96.6%, p < 0.01), DFS (42.6 vs. 91.6%, p < 0.01) and OS (65.2 vs. 91.5%, p < 0.01). No difference in mean HRCTV D 90 EQD 2 was seen between the groups ( p = 0.61). Conclusion Aside from known benefits of IGBT, MRI-based planning allows for assessment of tumor regression and prognosticates patients. [ABSTRACT FROM AUTHOR]

Background Vaginal cancer is an uncommon entity for which concurrent chemoradiation (CCRT) may be used based on small retrospective series and extrapolation from cervical cancer. We explored the adoption rate of CCRT and determined its impact on survival. Methods Patients entered into the National Cancer Data Base (NCDB) diagnosed with vaginal cancer from 1998 to 2011 who received definitive radiation therapy were included. Univariate/multivariable exploratory analyses of factors associated with CCRT were performed. Log-rank test and Cox proportional hazards modeling identified the contribution of CCRT on survival. Results Of the 13,689 patients identified, 8222 (60.1%) received radiation therapy. Of these, 3932 (47.8%) received CCRT and its use increased from 20.8% to 59.1% (1998-2011). Of the 23 patient, disease, facility, and treatment factors, 13 were significantly associated with patient outcomes and were entered into a binary logistic regression model. This evaluation revealed that younger age, larger tumor size, later year of diagnosis, higher facility volume, squamous histology, and higher stage (in order of increasing association) are independently associated with CCRT use. Median overall survival is longer with CCRT compared to radiation alone (56.2 vs. 41.2 months, p < 0.0005). On multivariable analysis, younger age, higher facility volume, squamous histology, lower comorbidity score, CCRT, brachytherapy utilization and lower stage (in order of increasing association) are independently prognostic of improved survival. Conclusions Use of CCRT for patients with vaginal cancer has increased and is associated with a significant improvement in survival in this large, national cohort. CCRT should be integrated into treatment guidelines for vaginal cancer. [ABSTRACT FROM AUTHOR]

Purpose: To compare the three-dimensional (3D) image (CT/MR)-based planning with a multichannel vaginal cylinder (MVC) to a single-channel vaginal cylinder (SVC) for the treatment of vaginal cancer. Methods and Materials: A total of 20 consecutive patients were treated with 3D CT/MR image-based high-dose-rate (HDR) brachytherapy using an MVC. All patients received external beam radiation therapy before HDR brachytherapy. A brachytherapy dose of 20–25Gy of more than five fractions was delivered to clinical target volume (CTV). Retrospectively, treatment plans for all patients were generated using the central channel only to mimic an SVC applicator. The SVC plans were optimized to match CTV coverage with MVC plans. Dose homogeneity index as well as bladder, rectum, sigmoid, and urethral doses were compared. Results: The mean D 90 for CTV was 74.2Gy (range: 48.8–84.1Gy). The mean (±standard deviation) of dose homogeneity index for MVC vs. SVC was 0.49 (±0.19) and 0.52 (±0.23), respectively (p =0.09). Mean bladder 0.1, 1, and 2cc doses for MVC vs. SVC were 69 vs. 71.2Gy (p =0.35), 61.4 vs. 63.8Gy (p =0.1), and 59.5 vs. 60.9Gy (p =0.31), respectively. Similarly, mean rectum 0.1, 1, and 2cc doses for MVC vs. SVC were 67.2 vs. 75.4Gy (p =0.005), 60.0 vs. 65.6Gy (p =0.008), and 57.3 vs. 62.0Gy (p =0.015), respectively, and mean sigmoid doses were 56.3 vs. 60.5Gy (p =0.10), 50.9 vs. 53.1Gy (p =0.09), and 49.1 vs. 50.7Gy (p =0.10), respectively. Conclusion: The 3D CT-/MR-based plan with MVC may provide better dose distribution in the management of certain clinical situations of vaginal cancer requiring intracavitary brachytherapy, especially in minimizing potential late rectal complications. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Chemosensitizing radiation with brachytherapy is standard of care for treatment of locally advanced cervical cancer, an increasingly rare disease. Treatment facility volume has been correlated with outcome in many diseases. Treatment outcome and likelihood of receiving standard therapy in locally advanced cervical cancer based on facility volume were examined using a large national cancer database. Methods: The National Cancer Data Base was queried for patients with stage IIB – IIIB cervical cancer from 1/1998 through 12/2010. Facility volumes were tallied. Overall survival was estimated using Kaplan–Meier method. Univariate and multivariable analyses were performed to determine variables affecting survival, receiving standard therapy, and total duration of radiotherapy. Results: We identified a total of 27,660 patients who were treated at 1361 facilities. Thirty of the facilities (2.2%) treated the highest quartile volume of patients (>9.4 patients annually) while 1072 facilities (78.8%) treated <2.4 patients annually. The median age of patients was 53, the majority were Caucasian, treated in a metropolitan area, and of squamous cell histology. Median survival of patients treated at lowest- and highest-volume centers were 42.3months (95% CI 39.8–44.8) and 53.8months (50.1–57.5), respectively (p <0.001). The proportions of patients receiving brachytherapy and chemotherapy were 54.8% and 79.9%, respectively. On multivariable analysis, higher facility volume independently predicted improved survival (p =0.022), increased likelihood of receiving brachytherapy (p <0.0005) and chemotherapy (p =0.013), and shorter time to radiotherapy completion (p <0.0005). Conclusions: Patients with locally advanced cervical cancer treated at high volume centers are more likely to receive standard therapy, complete therapy sooner, and experience better survival. [Copyright &y& Elsevier]

Purpose: Accelerated partial breast irradiation (APBI) with balloon and catheter-based brachytherapy has gained increasing popularity in recent years and is the subject of ongoing phase III trials. Initial data suggest promising local control and cosmetic results in appropriately selected patients. Long-term data continue to evolve but are limited outside of the context of the American Society of Breast Surgeons Registry Trial. Methods and Materials: A retrospective review of 157 patients completing APBI after breast-conserving surgery and axillary staging via high-dose-rate 192Ir brachytherapy from June 2002 to December 2007 was made. APBI was delivered with a single-lumen MammoSite balloon-based applicator to a median dose of 34 Gy in 10 fractions over a 5-day period. Tumor coverage and critical organ dosimetry were retrospectively collected on the basis of computed tomography completed for conformance and symmetry. Results: At a median follow-up time of 5.5 years (range, 0-10.0 years), the 5-year and 7-year actuarial incidences of ipsilateral breast control were 98%/98%, of nodal control 99%/98%, and of distant control 99%/99%, respectively. The crude rate of ipsilateral breast recurrence was 2.5% (n=4); of nodal failure, 1.9% (n=3); and of distant failure, 0.6% (n=1). The 5-year and 7-year actuarial overall survival rates were 89%/86%, with breast cancer–specific survival of 100%/99%, respectively. Good to excellent cosmetic outcomes were achieved in 93.4% of patients. Telangiectasia developed in 27% of patients, with 1-year, 3-year, and 5-year actuarial incidence of 7%/24%/33%; skin dose >100% significantly predicted for the development of telangiectasia (50% vs 14%, P<.0001). Conclusions: Long-term single-institution outcomes suggest excellent tumor control, breast cosmesis, and minimal late toxicity. Skin toxicity is a function of skin dose, which may be ameliorated with dosimetric optimization afforded by newer multicatheter brachytherapy applicators and a more rigorous skin dose constraint of ≤100%. [Copyright &y& Elsevier]

Abstract: Purpose: The present study evaluates the severity and time to resolution of bowel symptoms in men undergoing prostate brachytherapy (PB) with cesium-131 (131Cs). Methods and Materials: A longitudinal, prospective study of patients who had undergone PB with 131Cs at a single institution was performed. All patients were asked to complete the Expanded Prostate Cancer Index Composite preoperatively and at 2 weeks and 1, 3, and 6 months postoperatively. Outcomes were analyzed using descriptive statistics and Student’s t test. Results: The first 142 patients to have undergone PB with 131Cs at our institution were included in the study. The mean Expanded Prostate Cancer Index Composite bowel summary score at baseline was 90.1±11.0 compared with 71.5±22.8 (p =0.000), 70.1±20.7, 87.1±13.8 (p =0.01), and 90.7±9.2 (p =0.70) at 2 weeks and 1, 3, and 6 months postoperatively, respectively. Conclusions: In men undergoing PB as monotherapy with 131Cs, bowel symptoms returned to baseline by 3 months after the procedure. For patients undergoing PB with 131Cs as part of combination therapy, bowel symptoms return to their post–external beam radiotherapy, pre-PB baseline by 3 months after the procedure. [ABSTRACT FROM AUTHOR]