Executive summary of the American Radium Society appropriate use criteria for management of uterine clear cell and serous carcinomas.

BACKGROUND: Uterine clear cell and serous carcinomas have a high propensity for locoregional and distant spread, tend to be more advanced at presentation, and carry a higher risk of recurrence and death than endometrioid cancers. Limited prospective data exist to guide evidence-based management of these rare malignancies. OBJECTIVE: The American Radium Society sought to summarize evidence-based guidelines developed by a multidisciplinary expert panel that help to guide the management of uterine clear cell and serous carcinomas. METHODS: The American Radium Society Appropriate Use Criteria presented in this manuscript were developed by a multidisciplinary expert panel using an extensive analysis of current published literature from peer-reviewed journals. A well-established methodology (modified Delphi) was used to rate the appropriate use of diagnostic and therapeutic procedures for the management of uterine clear cell and serous carcinomas. RESULTS: The primary treatment for non-metastatic uterine clear cell and serous carcinomas is complete surgical staging, with total hysterectomy, salpingo-oophorectomy, omentectomy, and lymph node staging. Even in early-stage disease, patients with uterine clear cell and serous carcinomas have a worse prognosis than those with type I endometrial cancers, warranting consideration for adjuvant therapy regardless of the stage. Given the aggressive nature of these malignancies, and until further research determines the most appropriate adjuvant therapy, it may be reasonable to counsel patients about combined-modality treatment with systemic chemotherapy and radiotherapy. CONCLUSION: Patients diagnosed with uterine clear cell and serous carcinomas should undergo complete surgical staging. Multimodal adjuvant therapies should be considered in the treatment of both early-stage and advanced-stage disease. Further prospective studies or multi-institutional retrospective studies are warranted to determine optimal sequencing of therapy and appropriate management of patients based on their unique risk factors. Long-term surveillance is indicated due to the high risk of locoregional and distant recurrence.

Executive summary of the American Radium Society® Appropriate Use Criteria for management of uterine carcinosarcoma.

OBJECTIVE: Uterine carcinosarcomas (UCS) represent a rare but aggressive subset of endometrial cancers, comprising <5% of uterine malignancies. To date, limited prospective trials exist from which evidence-based management of this rare malignancy can be developed. METHODS: The American Radium Society Appropriate Use Criteria presented in this manuscript are evidence-based guidelines developed by a multidisciplinary expert panel for management of women with UCS. An extensive analysis of current medical literature from peer-reviewed journals was performed. A well-established methodology (modified Delphi) was used to rate the appropriate use of imaging and treatment procedures for the management of UCS. These guidelines are intended for the use of all practitioners who desire information about the management of UCS. RESULTS: The majority of patients with UCS will present with advanced extra uterine disease, with 10% presenting with metastatic disease. They have worse survival outcomes when compared to uterine high-grade endometrioid adenocarcinomas. The primary treatment for non-metastatic UCS is complete surgical staging with total hysterectomy, salpingo-oophorectomy and lymph node staging. Patients with UCS appear to benefit from adjuvant multimodality therapy to reduce the chance of tumor recurrence with the potential to improve overall survival. CONCLUSION: Women diagnosed with uterine UCS should undergo complete surgical staging. Adjuvant multimodality therapies should be considered in the treatment of both early- and advanced stage patients. Long-term surveillance is indicated as many of these women may recur. Prospective clinical studies of women with UCS are necessary for optimal management.

Using flattening filter free beams in electronic tissue compensation whole breast irradiation with deep inspiration breath hold.

PURPOSE: In order to reduce heart dose, DIBH has become a common practice in left-sided whole breast irradiation. This technique involves a significant strain on patients due to the breath-hold requirements. We hereby investigate the dosimetric and delivery feasibility of using flattening filter free (FFF) energies with electronic tissue compensation (ECOMP) planning technique to reduce the required breath-hold lengths and increase patient compatibility. METHODS: Fifteen left-sided, postlumpectomy patients previously receiving DIBH whole-breast radiotherapy (266cGy x 16fx) were retrospectively planned using ECOMP for both 6X and 6X-FFF. A dosimetric comparison was made between the two plans for each patient using various dosimetric constraints. Delivery feasibility was analyzed by recalculating the 6X ECOMP plan with 6X-FFF without replanning (6X-FFF QA) and delivering both plans for a one-to-one comparison using Gamma analysis. Beam-on times for the 6X and 6X-FFF plans were measured. For all tests, Wilcoxon signed-rank test was used with P < 0.05 as significant. RESULTS: No statistical difference was observed between 6X and 6X-FFF plans for most dosimetric endpoints except contralateral breast Dmax (P = 0.0008) and skin Dmax (p = 0.03) and Dmin (P = 0.01) for which 6X-FFF showed favorable results when compared with 6X. 6X-FFF significantly reduced beam-on times for all patients by 22%-42% (average 32%). All plan QAs passed departmental gamma criteria (10% low-dose threshold, 3%/3mm, >95% passing). CONCLUSION: ECOMP planning with FFF was found feasible for left-sided breast patients with DIBH. Plan quality is comparable, if not better, than plans using flattened beams. FFF ECOMP could significantly reduce beam-on time and required breath-hold lengths thereby increasing patient compatibility for this treatment while offering satisfactory plan quality and delivery accuracy.

Prostate bed target interfractional motion using RTOG consensus definitions and daily CT on rails : Does target motion differ between superior and inferior portions of the clinical target volume?

PURPOSE: Using high-quality CT-on-rails imaging, the daily motion of the prostate bed clinical target volume (PB-CTV) based on consensus Radiation Therapy Oncology Group (RTOG) definitions (instead of surgical clips/fiducials) was studied. It was assessed whether PB motion in the superior portion of PB-CTV (SUP-CTV) differed from the inferior PB-CTV (INF-CTV). PATIENTS AND METHODS: Eight pT2-3bN0-1M0 patients underwent postprostatectomy intensity-modulated radiotherapy, totaling 300 fractions. INF-CTV and SUP-CTV were defined as PB-CTV located inferior and superior to the superior border of the pubic symphysis, respectively. Daily pretreatment CT-on-rails images were compared to the planning CT in the left-right (LR), superoinferior (SI), and anteroposterior (AP) directions. Two parameters were defined: "total PB-CTV motion" represented total shifts from skin tattoos to RTOG-defined anatomic areas; "PB-CTV target motion" (performed for both SUP-CTV and INF-CTV) represented shifts from bone to RTOG-defined anatomic areas (i. e., subtracting shifts from skin tattoos to bone). RESULTS: Mean (± standard deviation, SD) total PB-CTV motion was -1.5 (±â€¯6.0), 1.3 (±â€¯4.5), and 3.7 (±â€¯5.7) mm in LR, SI, and AP directions, respectively. Mean (±â€¯SD) PB-CTV target motion was 0.2 (±1.4), 0.3 (±2.4), and 0 (±3.1) mm in the LR, SI, and AP directions, respectively. Mean (±â€¯SD) INF-CTV target motion was 0.1 (±â€¯2.8), 0.5 (±â€¯2.2), and 0.2 (±â€¯2.5) mm, and SUP-CTV target motion was 0.3 (±â€¯1.8), 0.5 (±â€¯2.3), and 0 (±â€¯5.0) mm in LR, SI, and AP directions, respectively. No statistically significant differences between INF-CTV and SUP-CTV motion were present in any direction. CONCLUSION: There are no statistically apparent motion differences between SUP-CTV and INF-CTV. Current uniform planning target volume (PTV) margins are adequate to cover both portions of the CTV.

Proton radiotherapy for gynecologic neoplasms.

BACKGROUND: Proton beam therapy (PBT) is increasingly being used globally to treat a variety of malignancies. This is the first review assessing PBT for gynecologic neoplasms. Dose distribution to organs-at-risk (OARs), particularly bone marrow (BM), is addressed. Clinical outcomes and toxicity data are detailed. MATERIAL AND METHODS: Systematic searches of PubMed, EMBASE, abstracts from meetings of the American Society for Radiation Oncology, Particle Therapy Co-Operative Group, and American Society of Clinical Oncology were conducted for publications. There were no restrictions on publication dates. Sixteen original investigations were identified and analyzed for this review. RESULTS: The available evidence for PBT in treating gynecologic cancers is of both low quantity and quality. The most studied scenarios for PBT include treatment of para-aortic lymph nodes, re-irradiation, and as an alternative to brachytherapy, and these also represent indications with the greatest opportunity for demonstrating as yet unproven toxicity reductions. Dosimetric studies have shown significantly decreased dose to OARs, such as the rectum, bladder, bowel, kidneys, BM, and femoral heads. This dose reduction to OARs with PBT is more pronounced within the low-dose volumes than the higher dose volumes, which radiobiologically could be expected to lower second malignancy rates. Clinical data, though no level 1 evidence, show appropriate stage-specific tumor control and outcomes with PBT treatment, along with low toxicity rates. CONCLUSION: The existing data, albeit limited, warrant and can help guide larger scale and higher quality studies addressing whether PBT could provide clinically meaningful differences in toxicities and outcomes in women with gynecologic neoplasms.

ACR Appropriateness Criteria® Adjuvant Management of Early-Stage Endometrial Cancer.

These consensus guidelines on adjuvant radiotherapy for early-stage endometrial cancer were developed from an expert panel convened by the American College of Radiology. The American College of Radiology Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method; and Grading of Recommendations Assessment, Development, and Evaluation, or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. After a review of the published literature, the panel voted on three variants to establish best practices for the utilization of imaging, radiotherapy, and chemotherapy after primary surgery for early-stage endometrial cancer.

ACR Appropriateness Criteria® Adjuvant Therapy in Vulvar Cancer.

These American College of Radiology consensus guidelines were formed from an expert panel on the appropriate use of adjuvant therapy in vulvar cancer after primary treatment with surgery. The American College of Radiology Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. The panel reviewed the pertinent literature in vulvar cancer and voted on three variants to establish appropriate use of imaging, adjuvant radiation, including dose, fields, and technique, as well as adjuvant chemotherapy. This report will aid clinicians in selecting appropriate patients for adjuvant treatment and will provide guidelines for the optimal delivery of adjuvant radiation therapy and chemotherapy.

Acr appropriateness Criteria management of vaginal cancer.

Due to its rarity, treatment guidelines for vaginal cancer are extrapolated from institutional reports and prospective studies of cervical and anal cancer. An expert panel was convened to reach consensus on the selection of imaging and therapeutic modalities. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) used by the panel to rate the appropriateness of imaging and treatment procedures. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Four variants were developed to represent clinical scenarios in vaginal cancer management. Group members reached consensus on the appropriateness of the pretreatment evaluation and therapeutic interventions. This article represents the consensus opinion of an expert panel and may be used to inform clinical recommendations in vaginal cancer management.

Diffuse lesions secondary to sarcoidosis mimicking widespread metastatic breast cancer: A case report.

This case of sarcoidosis mimicking metastatic breast cancer serves as a reminder of the need to consider differential diagnoses even when the clinical scenario and imaging findings are highly suggestive of metastases.

Percentage of Hormone Receptor Positivity in Breast Cancer Provides Prognostic Value: A Single-Institute Study.

BACKGROUND: A majority of breast cancer tumors express estrogen receptor (ER) and/or progesterone receptor (PR); however, the percentage of cancer cells expressing these receptors can range from 0-100%. The prognostic and therapeutic impact of the percentage of cells expressing hormone receptors in breast cancer is not fully understood. METHODS: A retrospective analysis of 411 breast cancer patients who were treated at the University of Nebraska Medical Center between 2010 and 2017 was performed. Patient tumors were evaluated for percentage of cells expressing ER and PR in conjunction with clinical outcomes. RESULTS: Patient tumors demonstrated a highly bimodal pattern of ER and PR staining with a majority of tumors demonstrating either a high percentage (> 80% of cells) or lack of cells (0%) staining for ER or PR. An increase in the percentage of ER positivity correlated with decreased local recurrence and improved overall survival. An increase in the percentage of PR positivity demonstrated a trend towards decreased local recurrence and improved overall survival, but was not statistically significant. CONCLUSIONS: Results based on both continuous and categorical evaluation of ER expression revealed that increasing expression correlated with improved patient outcomes. Similar evaluation of PR expression demonstrated a trend towards improved patient outcomes though not statistically significant. These findings suggest that the degree of hormone receptor positivity and not a Boolean representation of positivity could provide additional prognostic value in the treatment and management of breast cancer.

Can the Student Outperform the Master? A Plan Comparison Between Pinnacle Auto-Planning and Eclipse knowledge-Based RapidPlan Following a Prostate-Bed Plan Competition.

PURPOSE: Pinnacle Auto-Planning and Eclipse RapidPlan are 2 major commercial automated planning engines that are fundamentally different: Auto-Planning mimics real planners in the iterative optimization, while RapidPlan generates static dose objectives from estimations predicted based on a prior knowledge base. This study objectively compared their performances on intensity-modulated radiotherapy planning for prostate fossa and lymphatics adopting the plan quality metric used in the 2011 American Association of Medical Dosimetrists Plan Challenge. METHODS: All plans used an identical intensity-modulated radiotherapy beam setup and a simultaneous integrated boost prescription (68 Gy/56 Gy to prostate fossa/lymphatics). Auto-Planning was used to retrospectively plan on 20 patients, which were subsequently employed as the library to build an RapidPlan model. To compare the 2 engines' performances, a test set including 10 patients and the Plan Challenge patient was planned by both Auto-Planning (master) and RapidPlan (student) without manual intervention except for a common dose normalization and evaluated using the plan quality metric that included 14 quantitative submetrics ranging over target coverage, spillage, and organ at risk doses. Plan quality metric scores were compared between the Auto-Planning and RapidPlan plans using the Mann-Whitney U test. RESULTS: There was no significant difference between the overall performance of the 2 engines on the 11 test cases ( P = .509). Among the 14 submetrics, Auto-Planning and RapidPlan showed no significant difference on most submetrics except for 2. On the Plan Challenge case, Auto-Planning scored 129.9 and RapidPlan scored 130.3 out of 150, as compared with the average score of 116.9 ± 16.4 (range: 58.2-142.5) among the 125 Plan Challenge participants. CONCLUSION: Using an innovative study design, an objective comparison has been conducted between 2 major commercial automated inverse planning engines. The 2 engines performed comparably with each other and both yielded plans at par with average human planners. Using a constant-performing planner (Auto-Planning) to train and to compare, RapidPlan was found to yield plans no better than but as good as its library plans.

Multi-institutional review of repeat irradiation of chest wall and breast for recurrent breast cancer.

PURPOSE: To review the toxicity and clinical outcomes for patients who underwent repeat chest wall or breast irradiation (RT) after local recurrence. METHODS AND MATERIALS: Between 1993 and 2005, 81 patients underwent repeat RT of the breast or chest wall for locally recurrent breast cancer at eight institutions. The median dose of the first course of RT was 60 Gy and was 48 Gy for the second course. The median total radiation dose was 106 Gy (range, 74.4-137.5 Gy). At the second RT course, 20% received twice-daily RT, 54% were treated with concurrent hyperthermia, and 54% received concurrent chemotherapy. RESULTS: The median follow-up from the second RT course was 12 months (range, 1-144 months). Four patients developed late Grade 3 or 4 toxicity. However, 25 patients had follow-up >20 months, and no late Grade 3 or 4 toxicities were noted. No treatment-related deaths occurred. The development of Grade 3 or 4 late toxicity was not associated with any repeat RT variables. The overall complete response rate was 57%. No repeat RT parameters were associated with an improved complete response rate, although a trend was noted for an improved complete response with the addition of hyperthermia that was close to reaching statistical significance (67% vs. 39%, p = 0.08). The 1-year local disease-free survival rate for patients with gross disease was 53% compared with 100% for those without gross disease (p < 0.0001). CONCLUSIONS: The results of our study have shown that repeat RT of the chest wall for patients with locally recurrent breast cancer is feasible, because it is associated with acceptable acute and late morbidity and encouraging local response rates.

Incidence of tissue toxicities in gamma ray and fission neutron-exposed mice treated with Amifostine.

PURPOSE: To determine the effects of Amifostine or WR-151,327 on the incidence of lethal and non-lethal toxicities in a large cohort of mice exposed to gamma-ray or fission-spectrum neutron radiation. METHODS: To analyze data from 4000 B6CF1 mice which received a single whole body irradiation (WBI) with 206 cGy or 417 cGy cobalt-60 gamma rays or 10 cGy or 40 cGy of fission-spectrum neutrons (average energy 0.85 MeV) produced by the Janus reactor at Argonne National Laboratory. In the neutron cohort, Amifostine, WR-151,327, saline or nothing was injected once, intraperitoneally, 30 minutes before irradiation. In the cobalt-60 cohort, WR-151327 was omitted from the same protocol. At the time of natural death, tissue toxicities found in these mice were recorded, and these records were analyzed. While all previous studies focused on the modulation of life shortening effects of WBI by Amifostine, in this study we calculated changes in the frequencies of 59 tissue toxicities and changes in the total number of toxicities per animal. RESULTS: Amifostine protected against specific non-tumor pathological complications (67% of the non-tumor toxicities induced by gamma irradiation, 31% of the neutron induced specific toxicities), as well as specific tumors (56% of the tumor toxicities induced by gamma irradiation, 25% of the neutron induced tumors). Amifostine also reduced the total number of toxicities per animal for both genders in the gamma ray exposed mice and in males in the neutron exposed mice. CONCLUSIONS: Amifostine was protective against many, but not all, tissue toxicities caused by WBI gamma and neutron irradiation.

Accelerated partial breast radiotherapy: a review of the literature and future directions.

Breast conservation therapy exemplifies the tailoring of medicine in the care of patients with cancer. Akin to improvements in surgical approaches, accelerated partial breast irradiation (APBI) tailors the treatment volume and duration to the needs of well selected patients. Here, we examine the evidence supporting APBI as well as the lessons in patient selection, dose and delivery techniques. Examination of historical techniques and their associated outcomes will support more correct patient selection and treatment delivery in an era where we await the reports of several large prospective trials.

Inoperable pancreatic cancer: standard of care.

Inoperable pancreatic adenocarcinoma is a dilemma that oncologists frequently encounter. Only 15% to 20% of patients are diagnosed when cancer of the pancreas is still surgically resectable. However, pancreaticoduodenectomy is the only curative option for this disease and should be offered to all patients who meet resection criteria and do not have significant comorbidities. For inoperable pancreatic cancer, the goals of treatment are to palliate symptoms and prolong life. Improved survival in locally advanced disease has been demonstrated with chemoradiation plus fluorouracil or with gemcitabine (Gemzar) alone. In metastatic disease, single-agent gemcitabine has been associated with improvement in symptoms and survival. Trials combining various chemotherapeutic agents with gemcitabine have not had a significant impact on overall survival, although meta-analyses suggest a small benefit. The targeted agent erlotinib (Tarceva) has shown a modest improvement in overall survival in combination with gemcitabine. This combination is another option for first-line therapy in patients with locally advanced or metastatic disease. Despite these recent advances, survival for patients with inoperable pancreatic cancer continues to be poor. Future investigations need to focus on understanding the molecular nature of this malignancy, with the goal of developing interventions based on this knowledge.

Effects of etchants and primers on shear bond strength of a self-ligating esthetic orthodontic bracket.

INTRODUCTION: Damon 3 orthodontic brackets (Ormco, Orange, Calif), combining a self-ligating bracket with a composite bracket pad were the subject of an in-vitro bonding study to determine the shear bond strength to enamel and adhesive remaining on the teeth with various enamel and bracket preparation procedures. METHODS: A 3 x 2 factorial design was selected with the following factors as variations of the enamel preparation: liquid phosphoric acid etchant followed by primer (Ortho Solo; Ormco), gel phosphoric acid etchant followed by primer, and self-etching primer (Transbond Plus; 3M Unitek, Monrovia, Calif). The second factor was a primer (Ortho Solo) either applied to the bracket pad or absent as a control. RESULTS: No statistically significant differences were observed in shear bond strengths, with group average estimates ranging from 14.5 to 16.6 MPa. Debonding predominantly occurred at the bracket-pad interface with no significant differences in adhesive remaining on the teeth. CONCLUSIONS: This in-vitro study indicated that self-etching primer, gel etchant, and liquid etchant produce equal and sufficient bond strengths. Furthermore, application of primer to the bracket pad does not improve bond strength.

Discovery and characterization of small molecule Rac1 inhibitors.

Aberrant activation of Rho GTPase Rac1 has been observed in various tumor types, including pancreatic cancer. Rac1 activates multiple signaling pathways that lead to uncontrolled proliferation, invasion and metastasis. Thus, inhibition of Rac1 activity is a viable therapeutic strategy for proliferative disorders such as cancer. Here we identified small molecule inhibitors that target the nucleotide-binding site of Rac1 through in silico screening. Follow up in vitro studies demonstrated that two compounds blocked active Rac1 from binding to its effector PAK1. Fluorescence polarization studies indicate that these compounds target the nucleotide-binding site of Rac1. In cells, both compounds blocked Rac1 binding to its effector PAK1 following EGF-induced Rac1 activation in a dose-dependent manner, while showing no inhibition of the closely related Cdc42 and RhoA activity. Furthermore, functional studies indicate that both compounds reduced cell proliferation and migration in a dose-dependent manner in multiple pancreatic cancer cell lines. Additionally, the two compounds suppressed the clonogenic survival of pancreatic cancer cells, while they had no effect on the survival of normal pancreatic ductal cells. These compounds do not share the core structure of the known Rac1 inhibitors and could serve as additional lead compounds to target pancreatic cancers with high Rac1 activity.

A comprehensive dosimetric study on switching from a Type-B to a Type-C dose algorithm for modern lung SBRT.

BACKGROUND: Type-C dose algorithms provide more accurate dosimetry for lung SBRT treatment planning. However, because current dosimetric protocols were developed based on conventional algorithms, its applicability for the new generation algorithms needs to be determined. Previous studies on this issue used small sample sizes and reached discordant conclusions. Our study assessed dose calculation of a Type-C algorithm with current dosimetric protocols in a large patient cohort, in order to demonstrate the dosimetric impacts and necessary treatment planning steps of switching from a Type-B to a Type-C dose algorithm for lung SBRT planning. METHODS: Fifty-two lung SBRT patients were included, each planned using coplanar VMAT arcs, normalized to D95% = prescription dose using a Type-B algorithm. These were compared against three Type-C plans: re-calculated plans (identical plan parameters), re-normalized plans (D95% = prescription dose), and re-optimized plans. Dosimetric endpoints were extracted and compared among the four plans, including RTOG dosimetric criteria: (R100%, R50%, D2cm, V105%, and lung V20), PTV Dmin, Dmax, Dmean, V% and D90%, PTV coverage (V100%), homogeneity index (HI), and Paddick conformity index (PCI). RESULTS: Re-calculated Type-C plans resulted in decreased PTV Dmin with a mean difference of 5.2% and increased Dmax with a mean difference of 3.1%, similar or improved RTOG dose compliance, but compromised PTV coverage (mean D95% and V100% reduction of 2.5 and 8.1%, respectively). Seven plans had >5% D95% reduction (maximum reduction = 16.7%), and 18 plans had >5% V100% reduction (maximum reduction = 60.0%). Re-normalized Type-C plans restored target coverage, but yielded degraded plan conformity (average PCI reduction 4.0%), and RTOG dosimetric criteria deviation worsened in 11 plans, in R50%, D2cm, and R100%. Except for one case, re-optimized Type-C plans restored RTOG compliance achieved by the original Type-B plans, resulting in similar dosimetric values but slightly higher target dose heterogeneity (mean HI increase = 13.2%). CONCLUSIONS: Type-B SBRT lung plans considerably overestimate target coverage for some patients, necessitating Type-C re-normalization or re-optimization. Current RTOG dosimetric criteria appear to remain appropriate.

Still equivalent for dose calculation in the Monte Carlo era? A comparison of free breathing and average intensity projection CT datasets for lung SBRT using three generations of dose calculation algorithms.

PURPOSE: Inhomogeneity dose modeling and respiratory motion description are two critical technical challenges for lung stereotactic body radiotherapy, an important treatment modality for small size primary and secondary lung tumors. Recent studies revealed lung density-dependent target dose differences between Monte Carlo (Type-C) algorithm and earlier algorithms. Therefore, this study aimed to investigate the equivalence of the two most popular CT datasets for treatment planning, free breathing (FB) and average intensity projection (AIP) CTs, using Type-C algorithms, and comparing with two older generation algorithms (Type-A and Type-B). METHODS: Twenty patients (twenty-one lesions) were planned using a Type-A algorithm on the FB CT. Lung was contoured separately on FB and AIP CTs and compared. Dose comparison was obtained between the two CTs using four commercial dose algorithms including one Type-A (Pencil Beam Convolution - PBC), one Type-B (Analytical Anisotropic Algorithm - AAA), and two Type-C algorithms (Voxel Monte Carlo - VMC and Acuros External Beam - AXB). For each algorithm, the dosimetric parameters of the target (PTV, Dmin , Dmax , Dmean , D95, and D90) and lung (V5, V10, V20, V30, V35, and V40) were compared between the two CTs using the Wilcoxon signed rank test. Correlation between dosimetric differences and density differences for each algorithm were studied using linear regression and Spearman correlation, in which both global and local density differences were evaluated. RESULTS: Although the lung density differences on FB and AIP CTs were statistically significant (P = 0.003), the magnitude was small at 1.21 ± 1.45%. Correspondingly, for the two Type-C algorithms, target and lung dosimetric differences were small in magnitude and statistically insignificant (P > 0.05) for all but one instance, similar to the findings for the older generation algorithms. Nevertheless, a significant correlation was shown between the dosimetric and density differences for Type-C and Type-B algorithms, but not for the Type-A algorithm. CONCLUSIONS: With the capability to more accurately model inhomogeneity, Monte Carlo (Type-C) algorithms are sensitive to respiration-induced local and global tissue density changes and exhibit a strong correlation between dosimetric and density differences. However, FB and AIP CTs may still be considered equivalent for dose calculation in the Monte Carlo era, due to the small magnitude of lung density differences between these two datasets.

A comparison of clinical and radiologic outcomes between frame-based and frameless stereotactic radiosurgery for brain metastases.

PURPOSE: Modern experiences in stereotactic radiosurgery (SRS) report noninvasive frameless techniques as an effective alternative to frame-based SRS. Frameless techniques potentially increase positional uncertainty and planning target volume margins are frequently used. Here, we compare rates of local control and radiation necrosis in frameless versus frame-based SRS. METHODS AND MATERIALS: Ninety-eight patients (170 lesions) with radiologic and clinical follow-up were analyzed. Group 1 contained 34 patients (61 lesions) immobilized with an invasive stereotactic frame. Group 2 had 64 patients (109 lesions) immobilized with a frameless SRS mask. Patient, tumor, and treatment characteristics were recorded, as were intervals to local recurrence and radiation necrosis (asymptomatic and symptomatic). RESULTS: Median patient age was 59 years (range, 25-89), and Karnofsky performance scale was 80 (range, 50-100). Median radiologic and clinical follow-up was 6.5 months (range, 0.7-44.3) and 7 months (range, 0.7-45.7). A median of 2 tumors were treated per course (range, 1-5) with a median dose of 18 Gy (range, 13-24 Gy). The median time to local failure was not reached, and Kaplan-Meier estimates of local failure were not statistically significant between groups (P = .303). Actuarial 6-month local failure rates were 7.2% in group 1 and 12.6% in group 2 (P = .295), with 12-month local failure rates of 14.5% and 26.8% (P = .185), respectively. There was no statistically significant difference in symptomatic (P = .391) or asymptomatic (P = .149) radiation necrosis. Six-month radiation necrosis was 0% in group 1 and 1.6% in group 2 (P = .311) with 12-month rates of 20.2% and 3.8%, respectively (P = .059). Median time to necrosis was not reached in group 1, but was 44 months in group 2. CONCLUSIONS: Frameless SRS demonstrates clinical outcomes comparable to frame-based techniques with respect to local failure and radiation necrosis.