Jonathan B. Strauss

Comparison and consensus guidelines for delineation of clinical target volume for CT- and MR-based brachytherapy in locally advanced cervical cancer

OBJECTIVE To create and compare consensus clinical target volume (CTV) contours for computed tomography (CT) and 3-Tesla (3-T) magnetic resonance (MR) image-based cervical-cancer brachytherapy. METHODS AND MATERIALS Twenty-three experts in gynecologic radiation oncology contoured the same 3 cervical cancer brachytherapy cases: 1 stage IIB near-complete response (CR) case with a tandem and ovoid, 1 stage IIB partial response (PR) case with tandem and ovoid with needles, and 1 stage IB2 CR case with a tandem and ring applicator. The CT contours were completed before the MRI contours. These were analyzed for consistency and clarity of target delineation using an expectation maximization algorithm for simultaneous truth and performance level estimation (STAPLE), with κ statistics as a measure of agreement between participants. The conformity index was calculated for each of the 6 data sets. Dice coefficients were generated to compare the CT and MR contours of the same case. RESULTS For all 3 cases, the mean tumor volume was smaller on MR than on CT (P<.001). The κ and conformity index estimates were slightly higher for CT, indicating a higher level of agreement on CT. The Dice coefficients were 89% for the stage IB2 case with a CR, 74% for the stage IIB case with a PR, and 57% for the stage IIB case with a CR. CONCLUSION In a comparison of MR-contoured with CT-contoured CTV volumes, the higher level of agreement on CT may be due to the more distinct contrast medium visible on the images at the time of brachytherapy. MR at the time of brachytherapy may be of greatest benefit in patients with large tumors with parametrial extension that have a partial or complete response to external beam. On the basis of these results, a 95% consensus volume was generated for CT and for MR. Online contouring atlases are available for instruction at http://www.nrgoncology.org/Resources/ContouringAtlases/GYNCervicalBrachytherapy.aspx.

Results of the 2005-2008 association of residents in radiation oncology survey of chief residents in the United States: Clinical training and resident working conditions

PURPOSE To document clinical training and resident working conditions reported by chief residents during their residency. METHODS AND MATERIALS During the academic years 2005 to 2006, 2006 to 2007, and 2007 to 2008, the Association of Residents in Radiation Oncology conducted a nationwide survey of all radiation oncology chief residents in the United States. Chi-square statistics were used to assess changes in clinical training and resident working conditions over time. RESULTS Surveys were completed by representatives from 55 programs (response rate, 71.4%) in 2005 to 2006, 60 programs (75.9%) in 2006 to 2007, and 74 programs (93.7%) in 2007 to 2008. Nearly all chief residents reported receiving adequate clinical experience in commonly treated disease sites, such as breast and genitourinary malignancies; and commonly performed procedures, such as three-dimensional conformal radiotherapy and intensity-modulated radiotherapy. Clinical experience in extracranial stereotactic radiotherapy increased over time (p < 0.001), whereas clinical experience in endovascular brachytherapy (p <0.001) decreased over time. The distribution of gynecologic and prostate brachytherapy cases remained stable, while clinical case load in breast brachytherapy increased (p = 0.006). A small but significant percentage of residents reported receiving inadequate clinical experience in pediatrics, seeing 10 or fewer pediatric cases during the course of residency. Procedures involving higher capital costs, such as particle beam therapy and intraoperative radiotherapy, and infrequent clinical use, such as head and neck brachytherapy, were limited to a minority of institutions. Most residency programs associated with at least one satellite facility have incorporated resident rotations into their clinical training, and the majority of residents at these programs find them valuable experiences. The majority of residents reported working 60 or fewer hours per week on required clinical duties. CONCLUSIONS Trends in clinical training and resident working conditions over 3 years are documented to allow residents and program directors to assess their residency training.

Should uterine tandem applicators ever be placed without ultrasound guidance? No: a brief report and review of the literature.

Background: Brachytherapy is an integral component of the curative treatment of locally advanced cervical cancer. Optimal applicator placement is associated with improvements in local control and treatment-related toxicity. Uterine perforation by the tandem is common and often undetected by orthogonal radiographs. The role of ultrasound in guiding tandem placement remains controversial. Methods: A 55-year-old woman with International Federation of Gynecology and Obstetrics stage IIB cervix cancer underwent placement of a Fletcher-Suit-Delcos tandem and ovoids applicator. Postoperative computed tomography was used for treatment planning. Results: The applicator appeared to be appropriately placed on clinical exam and orthogonal radiographs. Postoperative computed tomography revealed the tandem had perforated the anterior uterine wall. In a second procedure, the tandem was placed correctly under intraoperative ultrasonography. Conclusions: A review of the literature finds a relatively high rate of uterine perforation of the uterus that is undetected by orthogonal radiographs or clinical examination. Multiple reports support the use of real-time ultrasound for patients with especially challenging anatomy. As this report illustrates, uterine perforation is possible in any patient. Therefore, routine real-time ultrasonography should be considered for all uterine tandem insertions.

A dosimetric comparison between the supine and prone positions for three-field intact breast radiotherapy.

Purpose: Supine tangential radiotherapy for the intact breast is a standard component of breast conservation management; a supraclavicular (SCV) field can be added for patients at high risk for nodal failure. Treatment in the prone position has demonstrated improvements in lung sparing, but has been limited to early-stage patients in whom radiation to only the breast was indicated. We sought to investigate the dosimetric feasibility of treating women in the prone position, using a 3-field monoisocentric technique. Methods: A total of 10 patients previously simulated supine and prone were selected for replanning. The heart, ipsilateral breast, contralateral breast, and axillary/SCV lymph node regions were contoured in accordance with Radiation Therapy Oncology Group guidelines. The 3-field monoisocentric plans were created for both the supine and prone scans. Target coverage, homogeneity, and organ at risk sparing were examined. Results: Both plans achieved acceptable coverage of the breast. The mean percentage of the breast receiving at least 95% of the prescription dose (V95%) were similar in the prone and supine positions, 89.3% versus 90.7% (P = 0.29). Mean V95% of the level 3 axilla and SCV were 93.8% versus 97.0% prone versus supine (P = 0.16). The percentage of ipsilateral lung receiving >20 Gy was substantially reduced from 21.2% supine to 9.3% prone (P = 0.001). Conclusion: Three-field radiotherapy in the prone position appears to be dosimetrically equivalent to supine treatment with respect to target coverage, but the prone position decreases lung dose.

Clinical Outcomes in International Federation of Gynecology and Obstetrics Stage IA Endometrial Cancer With Myometrial Invasion Treated With or Without Postoperative Vaginal Brachytherapy

PURPOSE To assess the clinical outcomes of patients with Stage IA endometrial cancer with myometrial invasion treated with postoperative vaginal brachytherapy (VBT) with those who received no adjuvant therapy (NAT). METHODS AND MATERIALS All patients treated with hysterectomy for endometrial cancer at Northwestern Memorial Hospital between 1978 and 2005 were identified. Those patients with Stage IA disease with myometrial invasion who were treated with VBT alone or NAT were identified and included in the present analysis. RESULTS Of 252 patients with Stage IA endometrial cancer with superficial (<50%) myometrial invasion who met the inclusion criteria, 169 underwent VBT and 83 received NAT. The median follow-up in the VBT and NAT groups was 103 and 61 months, respectively. In the VBT group, 56.8% had Grade 1, 37.9% had Grade 2, and 5.3% had Grade 3 tumors. In the NAT group, 75.9%, 20.5%, and 3.6% had Grade 1, 2, and 3 tumors, respectively. Lymphatic or vascular space invasion was noted in 12.4% of the VBT patients and 5.6% of the NAT patients. The 5-year overall survival rate was 95.5%. The 5-year recurrence-free survival rate was 92.4% for all patients, 94.4% for the VBT group, and 87.4% for the NAT group (p = NS). Of the 169 VBT patients and 83 NAT patients, 8 (4.7%) and 6 (7.2%) developed recurrent disease. One vaginal recurrence occurred in the VBT group (0.6%) and three in the NAT group (3.8%). Recurrences developed 2-102 months after surgical treatment. Two of the four vaginal recurrences were salvaged. No Grade 3 or higher acute or late radiation toxicity was noted. CONCLUSIONS The use of postoperative VBT in patients with Stage I endometrial cancer with <50% myometrial invasion yielded excellent vaginal disease control and disease-free survival, with minimal toxicity.

Patterns of recurrence and role of pelvic radiotherapy in ovarian clear cell adenocarcinoma.

Objective(s) The aims of this study were to analyze patterns of recurrence in patients with ovarian clear cell adenocarcinoma (CCA) and to evaluate the role of pelvic radiotherapy (RT). Methods and Materials All patients with ovarian CCA treated at a single institution between 1989 and 2012 were identified, and their medical records were reviewed. Eligibility criteria included histologic diagnosis of pure CCA of the ovary, surgical staging for International Federation of Gynecology and Obstetrics stage I-to-IIIC disease, and adjuvant or neoadjuvant chemotherapy. Selected end points were 3-, 5-, and 8-year cumulative incidence of pelvic recurrence (CIPR). Results Fifty-six patients met eligibility criteria. Most received intravenous carboplatin and paclitaxel for a median of 6 cycles. Six patients (10.7%) received pelvic RT, and 50 (89.3%) did not. Pelvic RT patients had stage I-to-IIC disease. Median follow-up was 39 months (range, 1–69 months). For the group as a whole, 14 patients (25%) had initial disease recurrence involving the pelvis, whereas 6 (10.7%) had first recurrence outside the pelvis. Three-, 5- and 8-year CIPR were 28.2%, 38.5%, and 43.2%, respectively. There was no significant difference in 3-, 5-, or 8-year CIPR between the group of patients receiving RT (20%, 20%, and 20%) and a group of patients with stages I to IIC who did not receive RT (9.9%, 22.4%, and 30.2%), P = 0.22. During RT, patients developed mild grade 1-to-2 side effects. After RT, 1 patient developed lower extremity lymphedema with recurrent cellulitis. One patient who developed small bowel obstruction before RT developed small bowel radiation enteritis and obstruction after RT, ultimately requiring surgical intervention. Conclusions These findings suggest that ovarian CCA exhibits a propensity for pelvic recurrence after surgery and chemotherapy. RT, a local treatment that can effectively sterilize microscopic tumor cells, may benefit patients with this disease. Prospective studies with sufficient statistical power are warranted to further evaluate the role of RT.

Psoas muscle metastases in non-small cell lung cancer

Lung cancer is the leading cause of cancer-related death in the U.S. and often spreads via lymphatics or through hematogenous metastasis to the brain, bone and adrenal glands. Isolated metastases to skeletal muscle, including the psoas muscles, are very uncommon. The present report is a case series of three patients with psoas metastases from non-small cell lung cancer (NSCLC) and a review of the relevant literature. Three patients presented with psoas muscle metastases from NSCLC detected on diagnostic imaging. All patients were treated with radiotherapy to the psoas muscle, and two patients were treated with curative intent on an oligometastatic paradigm. Radiotherapy to the psoas muscle was effective and well tolerated.

Receipt of vaginal brachytherapy is associated with improved survival in women with stage I endometrioid adenocarcinoma of the uterus: A National Cancer Data Base study.

Randomized controlled trials have consistently shown that the use of postoperative radiotherapy (RT) for stage I endometrial cancer leads to a reduction in the incidence of pelvic recurrences without a corresponding reduction in overall mortality. It was hypothesized that a reduction in mortality associated with the receipt of RT could be identified in a large data set with greater statistical power.

ACR appropriateness criteria® definitive therapy for early-stage cervical cancer

Objectives:The definitive treatment of early-stage cervical cancer involves multidisciplinary decision making. This expert panel was convened to reach consensus on the selection of appropriate therapies based on patient and disease characteristics at presentation. Methods: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) 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 the treatment. Results:Three clinical variants were developed to represent common scenarios in the treatment of early-stage cervical cancer. Group members reached consensus on the appropriateness of therapeutic options. This process yielded numerical ratings and descriptive commentary. Conclusions:This manuscript represents the consensus opinion of an expert panel based on a survey of all available medical literature. This manuscript may be used to inform the clinical decision making of physicians involved in the treatment of early-stage cervical cancer.

c-Met Overexpression in Cervical Cancer, a Prognostic Factor and a Potential Molecular Therapeutic Target.

Purpose: This study aimed to assess the association between pretreatment c-Met overexpression in local-regional advanced cervical cancer patients treated definitively with concurrent chemoradiation therapy (CRT) and treatment outcomes including overall survival (OS), progression-free survival (PFS), distant metastases (DM) control, and local-regional control (LC). Patients and Methods: This Institutional Review Board–approved study included cervical cancer patients treated definitively and consecutively with CRT. Evaluation of cytoplasmic immunoreactivity for c-Met was performed and scored semiquantitatively by 3 pathologists, blinded to the treatment outcomes, and incorporated both the intensity and percentage of immunoreactivity in invasive carcinoma (H score). Treatment outcomes were reviewed and reported. Outcomes were stratified by c-Met overexpression and tumor characteristics. OS, PFS, LC, and DC rates were obtained via the Kaplan-Meier method and differences between groups were evaluated by the log-rank test. Hazard ratios were obtained via Cox regression for both univariate and multivariate analyses. Results: The 5-year OS, PFS, LC, and DC were 57.18%, 48.07%, 72.11%, and 62.85%, respectively. Ten (35.7%) and 18 patients (64.3%) had c-Met H index >30 and<30, respectively. c-Met overexpression was significantly associated with worse 3- and 5-year OS (P=0.003), PFS (P=0.002), LC (P=0.01), and DC (P=0.0003). Patients with c-Met overexpression had a hazard ratio of 6.297, 5.782, 6.28, and 18.173 for the risks of death, disease progression, local recurrence, and DM, respectively. Conclusion: c-Met overexpression could be a potential predictive marker and therapeutic target for local-regional advanced cervical cancer patients treated definitively with CRT.