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Purpose: To determine the effect of dose and fractionation schedule of prophylactic cranial irradiation (PCI) on the incidence of chronic neurotoxicity (CNt) and changes in quality of life for selected patients with limited-disease small-cell lung cancer (LD SCLC).Methods and Materials: Patients with LD SCLC who achieved a complete response after chemotherapy and thoracic irradiation were eligible for randomization to undergo PCI to a total dose of 25 Gy in 10 daily fractions (Arm 1) vs. the experimental cohort of 36 Gy. Those receiving 36 Gy underwent a secondary randomization between daily 18 fractions (Arm 2) and twice-daily 24 fractions (Arm 3). Enrolled patients participated in baseline and follow-up neuropsychological test batteries along with quality-of-life assessments.Results: A total of 265 patients were accrued, with 131 in Arm 1, 67 in Arm 2, and 66 in Arm 3 being eligible. There are 112 patients (42.2%) alive with 25.3 months of median follow-up. There were no significant baseline differences among groups regarding quality-of-life measures and one of the neuropsychological tests, namely the Hopkins Verbal Learning Test. However, at 12 months after PCI there was a significant increase in the occurrence of CNt in the 36-Gy cohort (p=0.02). Logistic regression analysis revealed increasing age to be the most significant predictor of CNt (p=0.005).Conclusions: Because of the increased risk of developing CNt in study patients with 36 Gy, a total PCI dose of 25 Gy remains the standard of care for patients with LD SCLC attaining a complete response to initial chemoradiation. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to determine whether a dose response exists for extrahepatic bile duct carcinoma (EBDC) when treated with increasingly higher radiation doses delivered via a combination of external beam radiation (EBRT) and high dose rate intracavitary brachytherapy (HDRIB). To establish the best tolerated dose of HDRIB.Methods and Materials: Eighteen patients with pathologically proven, locoregional but unresectable or incompletely resected EBDC were studied from 1991-1998 in this phase I/II trial. All patients received EBRT, delivered via megavoltage photons at standard fractionation schedules, for a total dose of 45 Gy. The HDRIB was delivered using the nucleotron HDR remote afterloading unit with a 10 Ci Ir192 source. Each treatment of HDRIB delivered 7 Gy at 1 cm depth. The first group of eight patients received one treatment of HDRIB (Group 1, total dose = 52 Gy). The second group of six patients received two weekly treatments (Group 2, total dose = 59 Gy). The last group of four patients received three weekly treatments of HDRIB (Group 3, total dose = 66 Gy). HDRIB was delivered once weekly concomitant with the EBRT. Acute adverse reactions were evaluated after for each group of patients before escalating to the next higher dose level of HDRIB.Results: The median follow up time for all 18 patients was 15 months. The median survival for all 18 patients was 12.2 months (range 2 to 79.6 months). Overall two-year survival was 27.8%. Three patients (16.7%) had survival of more than 5 years. Dose response is suggested by the median survival of the three groups (9, 12.2, and 20.3 months for Group 1, 2, and 3, respectively), although this did not reach statistical significance. Complete or partial response (>50% reduction in tumor size) was seen in 25% of patients receiving total of 52 Gy compared to 80% of patients (5 patients in Group 2 and 3 patients in Group 3) receiving greater than 59 Gy (P = 0.05). No patients developed Grade 4 complications. One patient in Group 2 developed Grade 3 toxicity after second treatment of HDRIB.Conclusion: High dose rate brachytherapy of 21 Gy in three divided weekly treatments, plus 45 Gy of external beam radiation is well tolerated. A dose response is shown with significant increase of PR and CR rate for dose >59 Gy. This modality of treatment appears to be safe and effective for inoperable extrahepatic biliary duct carcinoma. [ABSTRACT FROM AUTHOR]

Objective: Delay in initiating cervical cancer treatment may impact outcomes. In a cohort of patients initially treated by surgery, chemoradiation, chemotherapy, or in a clinical trial, we aim to define factors contributing to prolonged time to treatment initiation., Methods: Data from patients initiating treatment for cervical cancer at a single institution was abstracted. Time to treatment initiation was defined as the interval from the date of cancer diagnosis to the date of treatment initiation. Poisson regression model was used for analysis., Results: Of 274 patients studied, the median time to treatment initiation was 60 days (range 0-551). The median times to initiate surgery (54 days, range 3-96) and chemoradiation (58 days, range 4-187) were not significantly different (relative risk (RR) 1.01, 95% CI 0.98 to 1.04, p=0.54). The shortest median initiation time was for chemotherapy (47 days; RR 1.13, 95% CI 1.08 to 1.19, p<0.0001) and the longest was for clinical trial (62 days; RR 1.18, 95% CI 1.12 to 1.24, p<0.0001). Charity care (RR 1.09, 95% CI 1.05 to 1.14, p<0.0001), Medicare or Medicaid (RR 1.10, 95% CI 1.06 to 1.14, p<0.0001), and self-pay (RR 1.38, 95% CI 1.32 to 1.45, p<0.0001) delayed treatment initiation more than private insurance. Hispanic White women (RR 0.69, 95% CI 0.66 to 0.73, p<0.0001) had a shorter treatment initiation time compared with non-Hispanic White patients, while Afro-Caribbean/Afro-Latina women (RR 0.86, 95% CI 0.81 to 0.90, p<0.0001) and African-American patients (RR 1.13, 95% CI 1.07 to 1.19, p<0.0001) had longer initiation times. Spanish speaking patients did not have a prolonged treatment initiation (RR 0.68, 95% CI 0.66 to 0.71, p<0.0001), though Haitian-Creole speaking patients did (RR 1.07, 95% CI 1.01 to 1.13, p<0.002). Diagnosis at an outside institution delayed treatment initiation time (RR 1.24, 95% CI 1.18 to 1.30, p<0.0001) compared with diagnosis at the cancer center., Conclusion: Factors associated with prolonged time to treatment initiation include treatment modality, insurance status, language spoken, and institution of diagnosis. By closely examining each of these factors, barriers to treatment can be identified and modified to shorten treatment initiation time., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2022. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Prophylactic radiotherapy (XRT) is a commonly used treatment to decrease heterotopic ossification (HO) in patients with traumatic hip injuries. We conducted a retrospective review of patients at risk for HO who underwent XRT. Of the patients reviewed, 27.3% developed radiographic HO, 11.2% developed symptoms, and 2.0% required resection surgery. Patients were divided into primary (n = 71) and secondary prophylaxis (n = 27) cohorts. In the primary group, 25.0% developed radiographic HO, 5.6% developed symptoms, and 0 required surgery. In the secondary cohort, 33.3% of patients developed new radiographic HO, and 25.9% were symptomatic: four had a Brooker score of 3, and three had a score of 4 (p = 0.03), and 7.4% required surgical resection. (Journal of Surgical Orthopaedic Advances 31(2):113-118, 2022).

Objectives: To examine the efficacy and safety of radiotherapy for the prevention of heterotopic ossification (HO) about the elbow., Design: Retrospective chart review., Setting: Level 1 trauma center., Patients/participants: Two hundred and twenty-nine patients who received prophylactic radiotherapy (XRT) over a 15-year period were identified. Patients were included if they received XRT to the elbow joint and had at least 12 weeks of follow-up after XRT. Fifty-four patients were ultimately included., Intervention: All patients were treated with a single dose of 7 Gy. Ninety-eight percentage of patients received XRT within 24 hours after surgery, and all patients received XRT within 72 hours after surgery., Main Outcomes Measurements: The primary study measures evaluated were the presence or absence of clinically symptomatic HO and the presence of radiographic HO after XRT to the elbow joint., Results: Eighteen patients were treated with XRT after a traumatic injury requiring surgery (primary prophylaxis), and 36 were treated with XRT after excision surgery to remove HO which had already formed (secondary prophylaxis). In the primary cohort, 16.7% developed symptomatic HO after XRT and 11.1% required surgery to resect the heterotopic bone. In the secondary cohort, 11.1% developed symptomatic HO after surgery and XRT and 5.5% required resection surgery. No secondary malignancies were identified., Conclusions: Our findings suggest that XRT for elbow HO may be safe and effective for both primary and secondary HO. XRT for HO was not shown to be associated with radiation-induced sarcoma in this series, at least in the short term. Further study in a large patient population with extended follow-up is required to better characterize populations at high risk for development of HO and secondary malignancy., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The Sedlis criteria define risk factors for recurrence warranting post-hysterectomy radiation for early-stage cervical cancer; however, these factors were defined for squamous cell carcinoma (SCC) at an estimated recurrence risk of ≥30%. Our study evaluates and compares risk factors for recurrence for cervical SCC compared with adenocarcinoma (AC) and develops histology-specific nomograms to estimate risk of recurrence and guide adjuvant treatment., Methods: We performed an ancillary analysis of GOG 49, 92, and 141, and included stage I patients who were surgically managed and received no neoadjuvant/adjuvant therapy. Multivariable Cox proportional hazards models were used to evaluate independent risk factors for recurrence by histology and to generate prognostic histology-specific nomograms for 3-year recurrence risk., Results: We identified 715 patients with SCC and 105 with AC; 20% with SCC and 17% with AC recurred. For SCC, lymphvascular space invasion (LVSI: HR 1.58, CI 1.12-2.22), tumor size (TS ≥4 cm: HR 2.67, CI 1.67-4.29), and depth of invasion (DOI; middle 1/3, HR 4.31, CI 1.81-10.26; deep 1/3, HR 7.05, CI 2.99-16.64) were associated with recurrence. For AC, only TS ≥4 cm, was associated with recurrence (HR 4.69, CI 1.25-17.63). For both histologies, there was an interaction effect between TS and LVSI. For those with SCC, DOI was most associated with recurrence (16% risk); for AC, TS conferred a 15% risk with negative LVSI versus a 25% risk with positive LVSI., Conclusions: Current treatment standards are based on the Sedlis criteria, specifically derived from data on SCC. However, risk factors for recurrence differ for squamous cell and adenocarcinoma of the cervix. Histology-specific nomograms accurately and linearly represent risk of recurrence for both SCC and AC tumors and may provide a more contemporary and tailored tool for clinicians to base adjuvant treatment recommendations to their patients with cervical cancer., Competing Interests: Declaration of Competing Interest Dr. Van Le reports royalties from Wolters Kluwer (as an editor of TeLinde's textbook). Dr. Huh reports money paid to him from consultancy with DYSIS. Dr. Miller reports money paid to him from consultancy with Tesaro, Eisai, Incyte, Karyopharm, and Genentech as well as money paid to his institution from Merck. He also reports money paid to his institution from grants or grants pending with nVision Medical, Advenchen, Forty Seven, Merck, Syros, and US BIOTEST. Dr. Ragab reports money paid to him from Consultancy with Regeneron. Dr. Viswanathan reports employment with money paid to her from Elsevier as the Ediotr in Chief for Seminars in Radiation Oncology. She also has an R01 NIH grant with money to her institution, and she received textbook royalties from Springer. Dr. Tewari has received money paid to him from consultancy with Clovis, Merck, Abbvie, Amgen, GSK, and Astra-Zenega, as well as payment for lectures from Clovis, Merck, Abbvie, Amgen, GSK, Astra-Zenega. Drs. Levinson, Fader, Beavis, Wolfson, Waggoner, Guntupalli, Lee, Kelly, McNally, Casablanca, Rositch, Spirtos, Wilkinson, Holman and Chris Purdy have no financial disclosures., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Delays in time to treatment initiation (TTI) with definitive radiation therapy (RT) or chemotherapy and RT (CRT) for cervical cancer could lead to poorer outcomes. This study investigates disparities in TTI and the impact of TTI on overall survival (OS)., Methods: Adult women with non-metastatic cervical squamous cell carcinoma diagnosed between 2004 and 2014, treated with definitive RT or CRT, and reported to the National Cancer Database were included. TTI was defined as days from diagnosis to start of RT or CRT. The impact of TTI on OS in patients treated with concurrent CRT which included brachytherapy was then assessed., Results: Overall, 14,924 patients were included (84.7% CRT, 15.3% RT). TTI was significantly longer for Non-Hispanic Black (NHB) (RR, 1.14; 95% CI, 1.11 to 1.18) and Hispanic women (RR, 1.19; 95% CI, 1.15 to 1.24) compared to Non-Hispanic White (NHW) women. Expected TTI (eTTI) for NHW, NHB, and Hispanic women were 38.1, 45.2, and 49.4days. eTTI rose from 36.2days in 2004 to 44.3days by 2014. Intensity-modulated radiation therapy (IMRT) was associated with increased eTTI of 46.5days versus 40.0days for non-IMRT. Longer TTI was not associated with inferior OS in patients treated with concurrent CRT., Conclusions: Delays in starting RT/CRT for cervical cancer increased from 2004 to 2014. Delays disproportionately affect NHB and Hispanic women. However, increased TTI was not associated with increased mortality for women receiving CRT. Further study of TTI's impact on other endpoints is warranted to determine if TTI represents an important quality indicator., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Electron beam therapy is a definitive radiation treatment option for superficial fibromatoses of the hands and feet. Because objective criteria for treatment response remain poorly defined, we sought to describe changes in electron beam treated lesions on MRI., Materials and Methods: The study included 1 male and 9 female patients with a total of 37 superficial fibromatoses; average age was 60.7 years. Standard 6 MeV electron beam treatment included 3 Gy per fraction for 10 or 12 treatments using split-course with 3-month halfway break. Pre- and post-treatment MRIs were evaluated to determine lesion size (cm3), T2 signal intensity and contrast enhancement (5-point ordinal scales) by a fellowship trained musculoskeletal radiologist. MRI findings were correlated with clinical response using a composite 1-5 ordinal scale, Karnofsky Performance Scale and patient-reported 10-point visual analog scale for pain., Results: Mean volume decreased from 1.5 to 1.2 cm 3 (p = 0.01, paired t-test). Mean T2 hyperintensity score decreased from 3.0 to 2.1 (p < 0.0001, Wilcoxon signed-rank). Mean enhancement score available for 22 lesions decreased from 3.8 to 3.0 (p < 0.0001, Wilcoxon signed-rank). Performance scores improved from 78.9 ± 13.7 to 84.6 ± 6.9 (p = 0.007, paired t-test). Pain scores decreased from 3.0 ± 3.3 to 1.1 ± 2.0 (p = 0.0001, paired t-test). Post-treatment T2 signal correlated weakly with performance and pain (Spearman's ρ = -0.37 and 0.16, respectively)., Conclusions: MRI is valuable for evaluating patients undergoing electron beam therapy for superficial fibromatoses: higher pretreatment T2 intensity may predict benefit from radiotherapy. T2 hypointensity may be a better marker than size for therapeutic effect.

Purpose: The perioperative management of primary extremity soft-tissue sarcomas (ESTS) is multidisciplinary including radiation therapy and chemotherapy (CT). The interplay between these modalities and the relative importance of each remain unclear. Our study aims to determine the relative impact of CT and radiotherapy on the outcome of ESTS patients treated with limb-sparing surgery., Materials and Methods: A retrospective review of ESTS registry yielded 97 patients who received neoadjuvant chemotherapy (NCT) and/or adjuvant CT with or without external-beam radiation therapy (EBRT) from January 1, 1999 through December 31, 2009. The cohort comprised 56 males and 41 females whose age at surgery ranged from 17 to 83 years (median, 56 y). Tumor characteristics included the following: 73 lower ESTS; 70 grade 3 lesions; 63 American Joint Committee on Cancer stage III tumors; and 27 lesions with positive microscopic margins. The following outcome parameters were evaluated for the patients' subgroups: overall survival (OS), locoregional control (LRC), and disease-free survival (DFS)., Results: EBRT was delivered postoperatively to 81 patients and 49 received CT. Median EBRT dose was 63 Gy (range, 50 to 72 Gy). At median follow-up of 54.6 months, the 5-year OS, LRC, DFS was 68.9%, 87.1%, 66.5%, respectively. On multivariate analysis, positive surgical margins negatively impacted LRC, DFS, and OS (hazard ratio [HR]=10.43, P=0.004), (HR=2.37, P=0.03), (HR=2.26, P=0.038), respectively. EBRT use improved LRC (HR=0.24, P=0.018) and DFS (HR=0.36, P=0.021). The impact of EBRT on DFS was retained (HR=0.28, P=0.006) in the high-grade ESTS subgroup who received CT. The 5-year local failure rate was 6.5%, 28.6%, and 22.2% (P=0.019) for patient receiving NCT, adjuvant chemotherapy, and no CT, respectively., Conclusion: Our data support the use of NCT followed by limb-sparing surgery and adjuvant EBRT in ESTS for local failure reduction with a trend toward improved DFS.

Cervical cancer is the fourth most common cause of cancer of women worldwide. In the developing world, it comprises 12% of all cancers of women. Since 1999, the mainstay of treatment for locally advanced cervical cancer (LACC) has been concurrent cisplatin-based chemoradiation. However, outcomes in this disease remain suboptimal, with long-term progression-free survival and overall survival rates of approximately 60%. There are several new strategies of combined modality treatment under evaluation in LACC, including chemotherapy before and after treatment as well as novel agents such as poly-adenosine diphosphate ribose polymerase inhibitors, antiangiogenic blockage, and immunotherapy. We provide a brief overview of these strategies and their potential in the treatment of women with LACC., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Ionizing radiation is an important treatment modality for a variety of malignant conditions. However, development of radiation-induced skin changes is a significant adverse effect of radiation therapy (RT). Cutaneous repercussions of RT vary considerably in severity, course, and prognosis. When they do occur, cutaneous changes to RT are commonly graded as acute, consequential-late, or chronic. Acute reactions can have severe sequelae that impact quality of life as well as cancer treatment. Thus, dermatologists should be informed about these adverse reactions, know how to assess their severity and be able to determine course of management. The majority of measures currently available to prevent these acute reactions are proper skin hygiene and topical steroids, which limit the severity and decrease symptoms. Once acute cutaneous reactions develop, they are treated according to their severity. Treatments are similar to those used in prevention, but incorporate wound care management that maintains a moist environment to hasten recovery. Chronic changes are a unique subset of adverse reactions to RT that may develop months to years following treatment. Chronic radiation dermatitis is often permanent, progressive, and potentially irreversible with substantial impact on quality of life. Here, we also review the etiology, clinical manifestations, pathogenesis, prevention, and management of late-stage cutaneous reactions to radiotherapy, including chronic radiation dermatitis and radiation-induced fibrosis.

Purpose: This study accessed the Surveillance, Epidemiology and End Results (SEER) database to determine if tumor size is an independent predictor of overall survival (OS) for patients with stages I and II vaginal cancer (VC)., Materials and Methods: We identified in the SEER database, patients with available tumor size having stage I or II squamous cell histology from January 2004 through December 2012 with minimum follow-up of six months. Univariate analyses (UA) and multivariable analyses (MVA) evaluated the effect of several prognostic factors, including tumor size, regarding OS., Results: 529 SEER patients were found with recorded tumor sizes, of which 293 (55.4%) were stage I and 236 (44.6%) stage II. UA found the following significant prognostic factors of worse OS: tumor size >2cm (HR=1.80, p=0.02) and older age at diagnosis (p<0.001) in stage I; and tumor size >2cm (HR=2.13, p=0.04) and older age at diagnosis (p<0.001) in stage II. Estimates of 5-year OS in patients with tumor size ≤2cm vs. >2cm were 79.2% vs. 66.1% in stage I (p=0.0187) and 80.9% vs. 51.2% in stage II (p=0.0369). MVA confirmed about double risk of death for patients with tumor size >2cm (HRs: 1.88 in stage I and 2.06 in stage II)., Conclusions: Tumor size seems to predict OS outcome in patients with stages I/II VC. Further confirmatory investigations are recommended to firmly establish its incorporation into currently accepted staging criteria for these patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: Patients with advanced stage endometrial carcinoma constitute a heterogeneous group of patients with different stages, tumor histologic types, and involved sites. Hysterectomy, bilateral salpingo-ophorectomy, and surgical staging are the cornerstone of surgical management in these patients. The optimal adjuvant therapy is yet to be established. An expert panel was convened to reach consensus on the most appropriate management options in this group of patients., Methods: 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., Results: Four clinical variants were developed to address common scenarios in the management of women with advanced-stage endometrial carcinoma. Group members reached consensus on the appropriateness of specific evaluation and treatment approaches with numerical ratings., Conclusions: In combining available medical literature and expert opinions, this manuscript may serve as an aid for other practitioners in the appropriate management of women with advanced-stage endometrial carcinoma.

Endometrial cancer is the most common gynecologic and the fourth most common malignancy in women in the United States. Cross-sectional imaging plays a vital role in pretreatment assessment of endometrial cancers and should be viewed as a complementary tool for surgical evaluation and planning of these patients. Although transvaginal US remains the preferred examination for the screening purposes, MRI has emerged as the modality of choice for the staging of endometrial cancer and imaging assessment of recurrence or treatment response. A combination of dynamic contrast-enhanced and diffusion weighted MRI provides the highest accuracy for the staging. Both CT and MRI perform equivalently for assessing nodal involvement or distant metastasis. PET-CT is more appropriate for assessing lymphadenopathy in high-grade FDG-avid tumors or for clinically suspected recurrence after treatment. An appropriate use and guidelines of imaging techniques in diagnosis, staging, and detection of endometrial cancer and treatment of recurrent disease are reviewed.The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every two 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.

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.

Objectives: Locoregionally advanced vulvar cancer (LRAVC) is a rare disease that presents many challenging medical decisions. An expert panel was convened to reach consensus on the most appropriate pretreatment assessment and therapeutic interventions in LRAVC patients., Methods: The American College of Radiology Appropriateness Criteria are evidenced-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 journal and the application of a well-established consensus methodology (modified Delphi) to rate 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 formulate recommendations., Results: Three clinical variants were developed to address common scenarios in the management of LRAVC. Group members reached consensus on the appropriateness of specific evaluation and treatment approaches, with numerical ratings and descriptive commentary., Conclusions: In combining available medical literature and expert opinion, this manuscript may serve as an aid for other practitioners in the appropriate management of patients with LRAVC.

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.

Purpose: To determine the maximum tolerated dose (MTD) and acute dose-limiting toxicities (DLT) of intravenous topotecan administered with weekly cisplatin during pelvic radiation therapy in patients with locally advanced cervical cancer., Methods: Patients were treated at one of two dose levels receiving intravenous topotecan at 0.5mg/m(2) and cisplatin at either 30 or 40 mg/m(2) given weekly for 6 weeks concurrently with pelvic radiation and intracavitary brachytherapy. The primary endpoint for the escalation study was acute dose-limiting toxicities occurring within 30 days of completing radiation therapy., Results: Eleven patients were enrolled. Dose-limiting toxicity consisting of Grade 3 nausea and vomiting lasting >24h in one patient and grade 3 febrile neutropenia in another patient occurred at the first dose level of weekly topotecan 0.5mg/m(2) and cisplatin 40 mg/m(2). This necessitated de-escalation to weekly cisplatin 30 mg/m(2) in combination with topotecan 0.5mg/m(2) and pelvic radiation. This dose level was tolerable in 6 evaluable patients with only one DLT consisting of grade 4 thrombocytopenia, grade 3 abdominal pain and grade 3 elevated gamma glutamyl transpeptidase (GGT)., Conclusions: In women with locally advanced cervical cancer, intravenous topotecan 0.5mg/m(2) and cisplatin 30 mg/m(2) given weekly for 6 weeks with concurrent pelvic radiation and intracavitary brachytherapy were tolerable. Further expansion of the feasibility cohort of this study was suspended based on the results of a phase 3 trial comparing the efficacy of platinum combinations in advanced and recurrent cervical cancer., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: The use of adjuvant treatment(s) following initial hysterectomy and retroperitoneal nodal harvesting of patients with clinical stage I and II cervical carcinoma is (are) presently based on the pathological assessment of surgical specimens. This report sought to delineate further the clinical application of potential therapeutic interventions and associated follow-up investigations of this patient cohort., Methods: The American College of Radiology (ACR) Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journal and the application of a well-established consensus methodology (modified Delphi) to rate 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., Results: From this process, 5 unique clinical variants were developed. These scenarios pertained to options of adjuvant radiation therapy and chemotherapy, methods of delivery of radiotherapy to optimize target volume coverage while simultaneously minimizing radiation exposure of adjacent healthy organs, and recommendations for patient follow-up care. Group members reached consensus of topic ratings in descending order of importance. A risk assessment breakdown was established to highlight the most likely indications for adjuvant treatment(s)., Conclusion: This assembly by the ACR of physicians involved in the management of patients with early stage cervical cancer was able to describe appropriateness criteria to aid other practitioners in selecting reasonable implementation of postoperative therapies and subsequent surveillance studies. These guidelines await further validation and refinement by both current and future prospectively randomized clinical studies regarding this patient population., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives. Mucosal melanomas are rarer than their cutaneous counterparts and are associated with a poorer prognosis. We report the clinical outcomes of patients with mucosal melanomas of the head and neck region generally treated with definitive surgery followed by postoperative radiation therapy (RT). Methods. We reviewed the records of 17 patients treated at the University of Miami in 1990-2007. Patients generally received conventionally fractionated RT regimens to the postoperative bed. Elective nodal RT was not routinely delivered. Eight patients received adjuvant chemotherapy or immunotherapy. Results. Median followup was 35.2 months (range 5-225). As the first site of failure: 3 patients recurred locally, 2 regionally and 2 distantly. All 3 patients who recurred locally had not received RT. Of the 5 locoregional recurrences, 4 were salvaged successfully with multimodality therapy with no evidence of disease at last followup. Overall survival was 64.7% at 2 years and 51.5% at 5 years. Conclusions. Patients with mucosal melanoma of the head and neck are best treated with surgery to achieve negative margins, followed by postoperative RT to optimize local control. Elective nodal irradiation may not be indicated in all cases, as regional failures were not predominant. Distant metastases were fewer when compared to historical data, potentially due to advancements in adjuvant therapies as well as aggressive multi-modality salvage at time of failure.

Purpose: To evaluate variability in the definition of preoperative radiotherapy gross tumor volume (GTV) and clinical target volume (CTV) delineated by sarcoma radiation oncologists., Methods and Materials: Extremity sarcoma planning CT images along with the corresponding diagnostic MRI from two patients were distributed to 10 Radiation Therapy Oncology Group sarcoma radiation oncologists with instructions to define GTV and CTV using standardized guidelines. The CT data with contours were then returned for central analysis. Contours representing statistically corrected 95% (V95) and 100% (V100) agreement were computed for each structure., Results: For the GTV, the minimum, maximum, mean (SD) volumes (mL) were 674, 798, 752±35 for the lower extremity case and 383, 543, 447±46 for the upper extremity case. The volume (cc) of the union, V95 and V100 were 882, 761, and 752 for the lower, and 587, 461, and 455 for the upper extremity, respectively. The overall GTV agreement was judged to be almost perfect in both lower and upper extremity cases (kappa=0.9 [p<0.0001] and kappa=0.86 [p<0.0001]). For the CTV, the minimum, maximum, mean (SD) volumes (mL) were 1145, 1911, 1605±211 for the lower extremity case and 637, 1246, 1006±180 for the upper extremity case. The volume (cc) of the union, V95, and V100 were 2094, 1609, and 1593 for the lower, and 1533, 1020, and 965 for the upper extremity cases, respectively. The overall CTV agreement was judged to be almost perfect in the lower extremity case (kappa=0.85 [p<0.0001]) but only substantial in the upper extremity case (kappa=0.77 [p<0.0001])., Conclusions: Almost perfect agreement existed in the GTV of these two representative cases. There was no significant disagreement in the CTV of the lower extremity, but variation in the CTV of upper extremity was seen, perhaps related to the positional differences between the planning CT and the diagnostic MRI., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To develop a Radiation Therapy Oncology Group (RTOG) atlas delineating gross tumor volume (GTV) and clinical target volume (CTV) to be used for preoperative radiotherapy of primary extremity soft tissue sarcoma (STS)., Methods and Materials: A consensus meeting was held during the RTOG meeting in January 2010 to reach agreement about GTV and CTV delineation on computed tomography (CT) images for preoperative radiotherapy of high-grade large extremity STS. Data were presented to address the local extension of STS. Extensive discussion ensued to develop optimal criteria for GTV and CTV delineation on CT images., Results: A consensus was reached on appropriate CT-based GTV and CTV. The GTV is gross tumor defined by T1 contrast-enhanced magnetic resonance images. Fusion of magnetic resonance and images is recommended to delineate the GTV. The CTV for high-grade large STS typically includes the GTV plus 3-cm margins in the longitudinal directions. If this causes the field to extend beyond the compartment, the field can be shortened to include the end of a compartment. The radial margin from the lesion should be 1.5 cm, including any portion of the tumor not confined by an intact fascial barrier, bone, or skin surface., Conclusion: The consensus on GTV and CTV for preoperative radiotherapy of high-grade large extremity STS is available as web-based images and in a descriptive format through the RTOG. This is expected to improve target volume consistency and allow for rigorous evaluation of the benefits and risks of such treatment., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To evaluate the feasibility of combining low-dose fractionated whole abdominal radiation (LDF-WAR) with weekly full-dose cisplatin (FD-CDDP) for patients with stage III/IV endometrial carcinoma., Methods: Patients with optimally debulked stage III/IV carcinoma of the endometrium (without extra-abdominal disease) were eligible for the study. Postoperatively, patients received the institutional standard systemic chemotherapy and vaginal brachytherapy. Patients then underwent experimental six weekly cycles of FD-CDDP (40 mg/m², maximum 70 mg IV) followed by LDF-WAR 6-8 hours after initiation of chemotherapy. In a conservative design, 6 patients were accrued to two sequential cohorts of LDF-WAR, at 0.5 Gy/fraction [Fx] (total 3 Gy) and 0.75 Gy/Fx (total 4.5 Gy). Toxicities and laboratory studies were evaluated at each visit., Results: Twelve patients were enrolled from January 2005 to June 2009 with median follow-up of 13.5 months (range: 5-27 months). Seventy-five percent of enrolled patients had uterine papillary serous histology. Eleven patients at least partially completed therapy (range: 2-6 cycles of FD-CDDP/LDF-WAR) with one additional patient opting out at the higher dose level. Combination therapy overall was well tolerated. Three patients in each cohort experienced grade 3 acute hematologic events with one recorded grade 4 toxicity in the second cohort. Of patients receiving any of the experimental treatment, five have experienced recurrences. Three of these patients were in cohort one and received 0.5 Gy/Fx LDF-WAR., Conclusion: Combination therapy with LDF-WAR as a novel chemopotentiator to FD-CDDP is a feasible adjuvant regimen in optimally debulked patients with stage III/IV endometrial carcinoma. Further investigation is warranted to determine treatment efficacy., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Single brain metastasis represents a common neurologic complication of cancer. Given the number of treatment options that are available for patients with brain metastasis and the strong opinions that are associated with each option, appropriate treatment for these patients has become controversial. Prognostic factors such as recursive partitioning analysis and graded prognostic assessment can help guide treatment decisions. Surgery, whole brain radiation therapy (WBRT), stereotactic radiosurgery or combination of these treatments can be considered based on a number of factors. Despite Class I evidence suggestive of best therapy, the treatment recommendation is quite varied among physicians as demonstrated by the American College of Radiology's Appropriateness Panel on single brain metastasis. Given the potential concerns of the neurocognitive effects of WBRT, the use of SRS alone or SRS to a resection cavity has gained support. Since aggressive local therapy is beneficial for survival, local control and quality of life, the use of these various treatment modalities needs to be carefully investigated given the growing number of long-term survivors. Enrollment of patients onto clinical trials is important to advance our understanding of brain metastasis., (Copyright 2010 American College of Radiology. Published by Mosby, Inc. All rights reserved.)

Objectives: This study was designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of weekly docetaxel with concurrent radiotherapy (RT) for the primary treatment of locally advanced squamous cell carcinoma of the cervix., Methods: Eligible patients included those with locally advanced squamous cell cervical cancer without para-aortic lymph node involvement. Docetaxel dose levels were 20 mg/m(2), 30 mg/m(2) and 40 mg/m(2) given intravenously weekly for 6 cycles. Three patients were to be treated at each dose level and 6 to receive the MTD., Results: Fifteen patients completed 4-6 cycles of chemotherapy. One of three patients experienced 2 delayed grade 3 severe adverse events (SAE) at the 20 mg/m(2) dose level consisting of colonic and ureteral obstruction. At the 30 mg/m(2) dose level, 1/4 patients had a probable treatment-related celiotomy due to obstipation and a necrotic tumor. Of the 8 patients treated at the 40 mg/m(2) dose level, 1 experienced grade 3 pneumonitis, likely treatment related. Overall, 10/15 (67%) experienced grade 1 or 2 diarrhea, 6 had grade 2 hematologic toxicity, and 2 had grade 2 hypersensitivity. 10 of 16 patients (67%) had no evidence of disease with follow-up ranging from 10-33 months (average 23 months)., Conclusions: The recommended phase II dose of docetaxel administered weekly with concurrent radiotherapy for locally advanced squamous cell carcinoma of the cervix is 40 mg/m(2).

Purpose: To look for possible associations between measurements of DNA index (DI), S-phase fraction (SPF), and tumor heterogeneity (TH) using flow cytometry and overall survival for patients with invasive cervical carcinoma treated with definitive irradiation., Methods and Materials: A total of 57 patients with International Federation of Obstetrics and Gynecology Stages IB(2) through IVB cervical carcinomas treated with definitive radiotherapy with or without concurrent chemotherapy were enrolled into this registry study that involved flow cytometric analysis of fresh tissue from each cervical cancer obtained by pretreatment biopsy. These specimens were evaluated for DNA aneuploidy (DI 1.5), SPF (15%), and TH (uniploid vs. multiploid)., Results: In these analyses 27 of the patients were treated in Radiation Therapy Oncology Group protocol 9001, and an additional 30 were offered chemoradiation at a single institution. Forty-one patients had DI 1.5. Twenty-nine patients had SPF 15%, and 2 had no determinable SPF. Forty-three patients had uniploid and 14 multiploid tumors. The 4-year estimated overall survival rate for the entire study cohort was 62% (95% confidence interval 48%-74%). With a median follow-up of 3.7 years, there were no observable associations by univariate analysis for DI, SPF, or TH concerning patient survival., Conclusions: There were no statistically significant associations among DI, SPF, or TH and patient outcome. Additional studies are indicated to identify tumor biomarkers that could predict patients at risk for disseminated disease.

Purpose: Primary treatment fails in >70% of locally advanced head and neck cancer patients. Salvage therapy has a 30-40% response rate, but few long-term survivors. Intensity-modulated radiotherapy (IMRT) has recently emerged as a new modality for salvage therapy. This retrospective study evaluated our experience using every-other-week IMRT with concurrent chemotherapy., Methods and Materials: Between 2001 and 2006, 41 patients underwent IMRT as repeat RT with concurrent chemotherapy. All but 6 patients received 60 Gy at 2 Gy/fraction. RT was delivered on an alternating week schedule., Results: With a median follow-up time of 14 months, the overall response rate was 75.6%, with a complete response and partial response rate of 58.5% and 17.1%, respectively. The Kaplan-Meier estimate of overall survival, disease-free survival, and progression-free survival at 24 months was 48.7%, 48.1%, and 38%, respectively. Patients who underwent surgery as a part of their salvage therapy had a mean estimated survival of 30.9 months compared with 22.8 months for patients who received only chemoradiotherapy (p = 0.126). Grade 3 or 4 acute toxicities occurred in 31.7% of patients, but all had resolved within 2 months of therapy completion. No deaths occurred during treatment, except for 1 patient, who died shortly after discontinuing treatment early because of previously undiagnosed metastatic disease; 6 patients had long-term complications., Conclusions: Concurrent chemotherapy with repeat radiotherapy with IMRT given every other week appears to be both well tolerated and feasible in patients treated with previous radiotherapy for recurrent head and neck cancer. IMRT represents a reasonable modality for reducing treatment-related toxicities in a repeat RT setting.

Purpose: After initial surgery, there has been no established consensus regarding adjunctive therapy for patients with uterine carcinosarcoma (CS). This study was designed to compare patient outcome following treatment with adjuvant whole abdominal irradiation (WAI) versus (vs.) chemotherapy for patients with this rare group of female pelvic malignancies., Patients and Methods: Eligible, consenting women with stage I-IV uterine CS, no more than 1 cm postsurgical residuum and/or no extra-abdominal spread had their treatments randomly assigned as either WAI or three cycles of cisplatin (C), ifosfamide (I), and mesna (M)., Results: 232 patients were enrolled, of whom 206 (WAI=105; CIM=101) were deemed eligible. Patient demographics and characteristics were similar between arms. FIGO stage (both arms) was: I=64 (31%); II=26 (13%); III=92 (45%); IV=24 (12%). The estimated crude probability of recurring within 5 years was 58% (WAI) and 52% (CIM). Adjusting for stage and age, the recurrence rate was 21% lower for CIM patients than for WAI patients (relative hazard [RH]=0.789, 95% confidence interval [CI]: (0.530-1.176), p=0.245, 2-tail test). The estimated death rate was 29% lower among the CIM group (RH=0.712, 95% CI: 0.484-1.048, p=0.085, two-tail test)., Conclusion: We did not find a statistically significant advantage in recurrence rate or survival for adjuvant CIM over WAI in patients with uterine CS. However, the observed differences favor the use of combination chemotherapy in future trials.

For over 4 decades, the delivery of definitive radiotherapy to patients with carcinoma of the cervix has involved both external beam and brachytherapy. Both of these therapeutic modalities have been traditionally linked to 2-dimensional radiographic guidance. Currently, the staging of these tumors still resides in clinical examinations and 2-dimensional diagnostic x-rays. Recently, there have been significant technological developments in imaging, namely magnetic resonance imaging and positron-emission tomography. These novel radiologic advances have subsequently led to a number of investigational studies, which in turn have shown a "paradigm shift" not only in the diagnosis but also in the radiation delivery used for patients with invasive carcinoma of the cervix.

Purpose of Review: The 5-year results of the Canadian multicenter prospectively randomized phase III trial that compared preoperative with postoperative radiotherapy for patients with extremity soft tissue sarcomas were recently presented at the 2004 meeting of the American Society of Clinical Oncology. These latter findings serve as an impetus for this current review to assess the optimal sequencing of adjuvant radiotherapy for such patients undergoing limb-preserving surgery., Recent Findings: The recent studies, including the 2004 American Society of Clinical Oncology presentation, described in this paper show no significant rise in the incidence of long-term side effects, such as delayed wound healing and subcutaneous tissue damage, in patients with extremity soft tissue sarcomas who receive once-daily preoperative irradiation followed by limb-preserving surgery. Postoperative radiotherapy may be best reserved for patients who are most likely to undergo a wide local excision with adequate (>10 mm) tumor-free margins (such as low-grade lesions in the lower extremities). There is an increasing use of neoadjuvant chemoradiation in this group of patients, especially for high-grade and large lesions., Summary: Further investigations regarding the preoperative management of extremity soft tissue sarcomas are continuing in an attempt to optimize the survival and functional status of these patients, while minimizing the permanent side effects resulting from such treatment.

Stereotactic radiosurgery has become a more widely employed modality of treatment for acoustic neuromas, but controversy still arises regarding the safety and efficacy of the technique. In general, radiation doses have been reduced over time. Since beginning treatments of acoustic neuromas with the Gamma Knife at the University of Miami/Jackson Memorial Medical Center in 1994, a dose regimen was adopted by the first author employing limited doses selected on the basis of tumor size with the anterior and medial regions of the prescription isodose surface kept just inside the gadolinium-enhanced limit of the tumor, in order to protect the facial nerve and brainstem. The records of patients treated for unilateral tumors were retrospectively reviewed. Fifty-two patients, aged 23-83 years, were treated with peripheral tumor doses of 10-14 Gy at the 45-70% isodoses. No patient developed new facial weakness or sensory loss; 3 patients had minor transient facial twitching within a few months of treatment. Of 34 patients followed more than 1 year (range 14-100 months, mean 43.4 months, median 37 months), 17 tumors reduced in size, 16 remained unchanged, and 1 increased in size. One patient, who had radiosurgery as planned postoperative adjuvant treatment after partial resection of a large tumor, developed an enlarging peritumoral arachnoid cyst that required surgical resection 79 months after radiosurgery. Patients with good pretreatment hearing retained approximately the same subjective level of hearing. Very good control of unilateral acoustic neuroma has been achieved by a limited-dose scheme that produces minimal complications, but due to the frequently indolent course of these tumors, continued long-term monitoring will be necessary., (2004 S. Karger AG, Basel.)

The standard low-dose-rate (LDR) delivery system utilized in the definitive management of patients with cervical carcinoma involves an intrauterine tandem and a pair of vaginal colpostats (ovoids). This well-known application system may deliver inadequate dosage if the tumor extends to the lower vaginal mucosa. During the gauze packing of the ovoids, either operator error or narrowing of the vaginal apex can result in mal-alignment of the colpostats and subsequent inadequate dosing to the ecto-cervix. A novel vaginal cylinder has been designed to address these concerns. Beginning January 1, 2001, patients with cancer of the cervix, endometrium, or vagina requiring LDR brachytherapy have been enrolled into an institutionally sanctioned clinical trial. As of May 31, 2001, a total of 11 patients have been entered but only 10 were successfully implanted with the test device. Patient follow-up has ranged from 0.81 years to 1.2 years (median: 0.96 years). Using our study applicator, all patients received within 10% of the preimplant prescribed dose to tumor. Also, no one had cumulative dosage that exceeded 10% of the maximum allowed dose to the critical normal tissues. Thus far, all study patients have had no clinical evidence of persistence/recurrence of disease or complications from treatment. The preliminary results presented herein clearly demonstrate the feasibility of this novel LDR vaginal cylinder in the treatment of a variety of clinical situations involving gynecological cancers. Our institutional trial is continuing.

Prophylactic cranial irradiation (PCI) has been demonstrated to significantly reduce the incidence of brain relapse from limited disease small-cell lung cancer (LD SCLC), but concerns about neurologic toxicity remain. The purpose of this report was to update a phase II institutional trial that explored the impact of twice-daily PCI on neurologic toxicity as well as outcome for this group of patients. All eligible subjects had documented complete response to induction chemotherapy and consolidative chest irradiation. The whole brain was treated with twice-daily fractions of 1.5 Gy with megavoltage irradiation to an approximate total dose of 30.0-36.0 Gy. Although not devised as a randomized study, approximately half of the eligible patients declined the protocol enrollment of their own volition and were retrospectively evaluated as a "historical" control group regarding the incidence of brain metastases. Fifteen patients accepted twice-daily PCI, with 12 deferring treatment. Median follow-up was 20 months. Disease-free survival at 2 years was 54% with twice-daily PCI versus 0% without any PCI (p = 0.013). Overall survival at 2 years was 62% with twice-daily PCI versus 23% without PCI (p = 0.032). No statistically significant neurologic deterioration was detected in the PCI group posttreatment. Thus, twice-daily PCI should be considered for patients with LD SCLC who achieve a complete response to chemoirradiation. A multi-institutional randomized trial would be necessary before making definitive recommendations.

Purpose: Because of previous reports of increased rate of recurrence and mortality after radiation therapy, eyelid sebaceous cell carcinoma has been considered radioresistant. Recent reports of success with primary radiation therapy have been attributed to advancements in irradiating technology and technique. Two cases of eyelid sebaceous cell carcinoma successfully treated with radiation therapy are reported. The techniques used are compared with the techniques described in previous reports, and factors favoring successful treatment are reevaluated., Methods: Case series and review of the literature. Two cases of eyelid sebaceous cell carcinoma that underwent radiation therapy are described. Both patients were offered, but refused, surgical excision. One patient received 69 Gy combined superficial and megavoltage x-ray irradiation to the left lower eyelid. The second patient received 59 Gy megavoltage electron beam irradiation to the right upper eyelid. A review of the literature was performed, and Fisher's exact test analysis was used to compare the results of all reported cases treated with < or =55 Gy with those treated with >55 Gy., Results: In both cases, the tumor responded to radiation therapy. One patient died 39 months after treatment, of myocardial infarction. The second patient is without clinical evidence of tumor recurrence 46 months after treatment. Fisher's exact test showed an advantage to patients treated with >55 Gy radiation (p = 0.05)., Conclusion: Radiation therapy with an appropriate delivery system is effective as a curative treatment for eyelid sebaceous cell carcinoma when >55 Gy of radiation dose is delivered. It should be considered for patients seeking an alternative to surgical excision.

High-risk endometrial cancer comprises an uncommon group of tumors, which includes pathological stage III adenocarcinoma and all stages of papillary serous carcinoma. Optimal management of this class of malignant female genital neoplasms is surgical resection, including debulking of any gross abdominopelvic disease. This article analyzes the literature concerning the use of adjunctive radiotherapy. The data presented suggest that postoperative whole abdominal radiotherapy may improve outcome in selected subsets of patients within this high-risk group. Future clinical investigations will greatly benefit from the anticipated published results of two completed prospective cooperative group clinical trials that involve whole abdominal irradiation.

This review of the present literature about the conventional management of patients with definitive radiotherapy for invasive carcinoma of the cervix will focus on advances in the use of external-beam radiation therapy (EBRT) as well as in the administration of low-dose-rate brachytherapy for the delivery of radiotherapy. Important concepts discussed include: techniques and dose fractionation for EBRT; newer imaging modalities for administration of EBRT; construction of the midline shield for external irradiation of the pelvic nodes following brachytherapy; the role of elective para-aortic nodal external radiotherapy; and the adequate number of brachytherapy applications needed to impact on patient outcome. Considerable attention will be given to multi-institutional clinical data (e.g., the Patterns of Care Study and the Radiation Therapy Oncology Group) to illustrate advances in radiotherapy of patients with cervical carcinoma.

Stereotactic irradiation (radiosurgery) is a method of precisely focusing well-defined beams of radiation at small intracranial targets. The technique has been applied to the treatment of brain lesions that are benign (e.g., arteriovenous malformations, meningiomas, pituitary adenomas) and malignant (e.g., gliomas, metastases). This paper introduces preliminary data suggesting the possible value of radiosurgery in the management of ovarian cancer metastatic to the brain. Among 32 women with ovarian cancer metastatic to the brain treated with whole brain irradiation, nine (29%) experienced a complete radiographic response, compared with two of the five patients (40%) treated with radiosurgery. The 2-year survival rate was 60% among those treated with radiosurgery and 15% among those who received whole brain irradiation without radiosurgical boost. Stereotactic irradiation may be of clinical benefit to select patients with brain metastases resulting from ovarian cancer. A prospective randomized trial has been implemented by the Radiation Therapy Oncology Group (RTOG 95-08) to determine whether such observations are reproducible on a national scale.

Purpose: To establish a typical value for radiation doses under pelvic midline shields., Materials and Methods: Three methods were used to determine bladder and rectal doses under 5- or 6-half-value layer (HVL) shields for 10- and 24-MV external beams. First, dose was computed with a standard irregular field routine in 25 consecutive patients (aged 35-70 years) with stage IIB or IIIB disease treated with cesium-137 brachytherapy followed by a parametrial external-beam boost. Second, in vivo measurements with a solid-state probe were recorded during the first boost after completion of brachytherapy in each patient. Third, measurements obtained with an ionization chamber in a solid phantom (water-equivalent material) were compared with computed and in vivo results., Results: All three dosimetric methods yielded bladder and rectal doses higher than the commonly assumed 5% of the unshielded primary beam dose. Doses within the shielded volume may be as high as 15% of the unshielded dose. Doses are similar under 5- and 6-HVL midline shields. Often, the actual bladder and rectal doses exceeded the planned dose limits and their corresponding maximum radiation dose tolerance levels., Conclusion: Bladder and rectal doses are higher than previously understood. Parametrial boosts may contribute as much as 3.0 Gy to the bladder and rectal doses.

This study analyzes a single-institution experience by evaluating the impact on survival of increasing total dose of adjunctive irradiation in patients who had extremity soft-tissue sarcoma (ESTS). A retrospective review of the tumor registry at a university medical center from January 1984 through December 1992 yielded a total of 59 surgical patients of ESTS. With follow-up ranging from 30 to 135 months (median, 65 months), the 2-, 5-, and 8-year overall and disease-free survival for all patients was 86%, 71%, 58% and 76%, 70%, 56%, respectively. Multivariate analyses using the Cox proportional hazards model revealed that total radiation dose (p = 0.02), American Joint Committee on Cancer stage (p = 0.04), and tumor size (p = 0.006) were all significant prognostic factors of overall survival; however, only tumor size was predictive of disease-free survival (p = 0.02). When the effect of tumor size and disease stage were controlled in the Cox model, a dose-response curve between increasing total radiation dose and improved overall patient survival was indicated. This study demonstrates the significance of tumor size on predicting both overall and disease-free survival in patients who have soft-tissue sarcomas of the extremity. It also suggests, however, that a radiation dose-response relation may exist for overall survival. Future investigations should consider evaluating the minimal total radiation dose needed to optimize patient survival after limb-sparing surgery.

Purpose/objective: To determine the prognostic factors for predicting outcome of patients with adenocarcinoma of the fallopian tube and to evaluate the impact of treatment modalities in managing this uncommon disease., Materials and Methods: A retrospective analysis of the tumor registries from 6 major medical centers from January 1, 1960 up to March 31, 1995 yielded 72 patients with primary adenocarcinoma of the fallopian tube. The Dodson modification of the FIGO surgical staging as it applies to carcinoma of the fallopian tube was utilized. Endpoints for outcome included overall and disease-free survival. Univariate analysis of host, tumor, and treatment factors was performed to determine prognostic significance, and patterns of failure were reviewed., Results: The median age of the study cohort was 61 years (range 30-79 years). Stage distribution was 24 (33%) Stage I; 20 (28%) Stage II; 24 (33%) Stage III; and 4 (6%) Stage IV. Adjuvant chemotherapy was administered to 54 (75%) patients, and postoperative radiotherapy was employed in 22 (31%). In the latter treatment group, 14 (64%) had whole pelvic external beam irradiation, 5 (23%) whole abdominal radiotherapy, 2 (9%) P-32 instillation, and 1 (4%) vaginal brachytherapy alone. Chemotherapy was used in 67% of Stage I and in 79% of Stages II/III/IV disease (not significant); radiotherapy was more commonly employed in Stage I than in Stages II/III/IV (46% vs. 23%, p = 0.05). The 5-, 8-, 15-year overall and disease-free survival for the study patients were 44.7%, 23.8%, 18.8% and 27.3%, 17%, 14%, respectively. Significant prognostic factors of overall survival included Stage I vs. II/III/IV (p = 0.04) and age < or = 60 years vs. > 60 years at diagnosis (p = 0.03). Only Stage I vs. II/III/IV (p = 0.05) was predictive of disease-free survival. Patterns of failure included 18% pelvic, 36% upper abdominal, and 19% distant. For all patients, upper abdominal failures were more frequently found in Stages II/III/IV (29%) than in Stage I (7%) (p = 0.03). Relapses solely outside of what would be included in standard whole abdominal radiotherapy portals occurred for only 15% of patients (6 of 40) with failures. Furthermore, patients having any recurrence, including the upper abdomen, were more likely (p = 0.001) to die (45%) than those without any type of relapse (18%)., Conclusion: This retrospective, multi-institutional study demonstrated the importance of FIGO stage in predicting the overall and disease-free survival of patients with carcinoma of the fallopian tube. Future investigations should consider exploring whole abdominal irradiation as adjunctive therapy, particularly in Stage II and higher.

We reviewed the results, in eight patients, of excision of heterotopic ossification about the elbow performed three to ten months (average, seven months) after the initial injury and followed by radiation therapy to prevent recurrence. The etiology of the heterotopic ossification included a neurological (head or spinal cord) injury in five patients and a local injury (fracture or fracture-dislocation) of the elbow in three patients. The average preoperative arc of motion of the three joints that were capable of motion was 12 degrees (5, 10, and 20 degrees); the remaining five joints were fixed in an average of 56 degrees (range, 10 to 90 degrees) of flexion. All of the patients received a total dose of radiation of 1000 centigray, divided into five fractions. The radiation therapy was instituted on the first postoperative day, and at least three of the remaining four treatments were administered on consecutive days. Radiation therapy was not performed on the weekend, so the five fractions were administered over the course of seven days. At an average of forty-six months (range, twenty-five to seventy-two months), the arc of motion averaged 103 degrees, which compared favorably with the 121-degree arc of motion that had been attained intraoperatively. Two patients who had residual motor deficits in the involved extremity had an arc of motion of 50 and 70 degrees at the latest follow-up evaluation; those who had normal motor function fared considerably better, averaging 118 degrees of motion. There was no substantial recurrence of ossification either radiographically or that limited motion, and no complications attributable to the radiation therapy were noted. On the basis of this experience, it seems that the generally recommended twelve to eighteen-month delay between injury and excision, to allow for maturation of heterotopic bone and thus to lessen the likelihood of recurrence, may be eliminated. Additional studies are needed to define the relative risk of recurrence in the various clinical settings in which heterotopic ossification is seen and to determine whether radiation therapy is necessary to prevent recurrence after early excision in each of these instances.

Progression of brain metastases after brain irradiation has prompted several studies on retreatment of the brain. Increased durations of survival and improved quality of life have been reported. Fifteen patients with previously treated brain metastases were entered into this pilot study between May 1990 and January 1994. All patients had neurologic and/or radiologic evidence of progression of brain metastases. The lung was the primary site in 60% of cases. The remaining 40% had breast, ovarian, and skin primaries. The median interval between the first treatment and retreatment was 10 months. All patients received whole-brain irradiation with or without a boost for their initial treatment course. Doses ranged from 3,000 to 5,500 cGy for initial treatments (median, 3,000). Retreatment consisted of limited fields with a median side equivalent square of 8.8 cm. Patients were retreated with a median dose of 3,000 cGy (range, 600-3,000 cGy). A median cumulative dose of 6,000 cGy was achieved. Retreatment consisted of twice-daily fractions (150 cGy/fraction). Retreatment was tolerated without serious complications. Of the 15 patients treated, nine (60%) experienced improvement, and five (27%) had stabilization of neurologic function and/or radiographic parameters. Median survival was 3.2 months; two of the reirradiated patients survived > or = 9 months. In conclusion, reirradiation is a viable option in patients with recurrent metastatic lesions of the brain, and the use of a limited retreatment volume makes this a well-tolerated, low-morbidity treatment that leads to clinical benefits and, in some instances, enhanced survival. The influence of hyperfractionation on the outcome needs to be investigated further in large series.

Purpose: An individualized midline shield (MLS) has been advocated for delivering homogeneous radiotherapy for patients with invasive cervical carcinoma. Yet, many radiation oncologists continue to employ a standard block. In the latter instance, any deviation of the cranial-caudal central axis of he tandem from the patient's midline could result in dose inhomogeneity to tumor. A retrospective review of a single university medical center's experience with constructing the MLS was initiated to determine the outcome of using a standard block vs. a customized block that conforms to the "Point A" isodose line. In addition, participating radiation oncologists associated with the Gynecologic Oncology Group (GOG) were polled to assess if there exists a consensus regarding midline block utilization in the management of cervical cancer patients which could be compared to the institutional study., Methods and Materials: From January 1, 1990 through December 31, 1992, 32 patients with invasive cervical carcinoma who underwent low dose rate brachytherapy at a single institution were identified. Patients were grouped as having a standard block (18 cases), customized block (5 cases), or no block (9 cases). The "Point A" isodose distribution from the implant was superimposed onto the whole pelvic simulation film and quantitatively compared to the actual or a hypothetical standard block outlined on the same radiograph. In September of 1995, 56 member and affiliated institutions in the GOG were surveyed concerning their use of a MLS, and the results were tabulated in December of 1995., Results: Approximately 72% of all cases (23 out of 32) at the single institution had tandem deviation ranging from 0-230 with a median of 50. This translated into a median percent overdosage to "Point A" Right of 15% and "Point A" Left of 12.5%. Although overall survival and incidence of chronic complications have not been affected by type of shielding, patient follow-up is limited with a median of 17.7 months (range: 4.2-58.9 months). Of the 56 surveyed radiation facilities in the GOG, 34 (61%) responded. One center was subsequently excluded as it performs only high dose rate brachytherapy. Of the evaluable respondents, 88% (29 out of 33) utilize a MLS in treating their patients with invasive cervical carcinoma. Of the latter group, 76% (22 out of 29), 21% (6 out of 29), and 3% (1 out of 29) employ a standard block, customized block, and a "step-wedge," respectively. For those using a standard block, 77% (17 out of 22) align the central cranial-caudal axis of the MLS along the corresponding midplane of the patient's pelvis on an anteroposterior radiograph rather than along the superior-inferior central axis of the tandem., Conclusions: This study suggests that the use of a standard midline shield could result in potential tumor dose inhomogeneity and should be avoided. A national survey of major academic centers further suggests that the majority of these facilities also utilize a rectangular central block that is not positioned with respect to possible tandem deviation. Further investigation concerning the techniques of midline shield construction should be considered.