Publications by authors named "Perry W Grigsby"

178 Publications

Standardized Uptake Value for F-Fluorodeoxyglucose Is a Marker of Inflammatory State and Immune Infiltrate in Cervical Cancer.

Clin Cancer Res 2021 Apr 5. Epub 2021 Apr 5.

Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.

Purpose: Chemoradiotherapy for locally advanced cervical cancer fails in over a third of patients. Biomarkers with therapeutic implications are therefore needed. We investigated the relationship between an established prognostic marker, maximum standardized uptake value (SUV) on F-fluorodeoxyglucose positron emission tomography, and the inflammatory and immune state of cervical cancers.

Experimental Design: An SUV most prognostic for freedom from progression (FFP) was identified and compared with known prognostic clinical variables in a cohort of 318 patients treated with definitive radiation with prospectively collected clinical data. Gene set enrichment analysis (GSEA) and CIBERSORT of whole-transcriptome data from 68 patients were used to identify biological pathways and immune cell subpopulations associated with high SUV. IHC using a tissue microarray (TMA, = 82) was used to validate the CIBERSORT findings. The impact of macrophages on cervical cancer glucose metabolism was investigated in coculture experiments.

Results: SUV <11.4 was most prognostic for FFP ( = 0.001). The GSEA showed that high SUV is associated with increased gene expression of inflammatory pathways, including JAK/STAT3 signaling. CIBERSORT and CD68 staining of the TMA showed high SUV tumors are characterized by a monocyte-predominant immune infiltrate. Coculture of cervical cancer cells with macrophages or macrophage-conditioned media altered glucose uptake, and IL6 and JAK/STAT3 signaling contribute to this effect.

Conclusions: SUV is a prognostic marker in cervical cancer that is associated with activation of inflammatory pathways and tumor infiltration of myeloid-derived immune cells, particularly macrophages. Macrophages contribute to changes in cervical cancer glucose metabolism.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-4450DOI Listing
April 2021

Targetability of cervical cancer by magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU)-mediated hyperthermia (HT) for patients receiving radiation therapy.

Int J Hyperthermia 2021 ;38(1):498-510

Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA.

Purpose: To evaluate the targetability of late-stage cervical cancer by magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU)-induced hyperthermia (HT) as an adjuvant to radiation therapy (RT).

Methods: Seventy-nine cervical cancer patients (stage IIIB-IVA) who received RT with lesions visible on positron emission tomography-computed tomography (PET-CT) were retrospectively analyzed for targetability using a commercially-available HT-capable MRgHIFU system. Targetability was assessed for both primary targets and/or any metastatic lymph nodes using both posterior (supine) and anterior (prone) patient setups relative to the transducer. Thirty-four different angles of rotation along subjects' longitudinal axis were analyzed. Targetability was categorized as: (1) Targetable with/without minimal intervention; (2) Not targetable. To determine if any factors could be used for prospective screening of patients, potential associations between demographic/anatomical factors and targetability were analyzed.

Results: 72.15% primary tumors and 33.96% metastatic lymph nodes were targetable from at least one angle. 49.37% and 39.24% of primary tumors could be targeted with patient laying in supine and prone positions, respectively. 25°-30° rotation and 0° rotation had the highest rate of the posterior and anterior targetability, respectively. The ventral depth of the tumor and its distance to the coccyx were statistically correlated with the anterior and posterior targetability, respectively.

Conclusion: Most late-stage cervical cancer primaries were targetable by MRgHIFU HT requiring either no/minimal intervention. A rotation of 0° or 25°-30° relative to the transducer might benefit anterior and posterior targetability, respectively. Certain demographic/anatomic parameters might be useful in screening patients for treatability.
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http://dx.doi.org/10.1080/02656736.2021.1895330DOI Listing
January 2021

Integrating imaging and RNA-seq improves outcome prediction in cervical cancer.

J Clin Invest 2021 Mar;131(5)

Department of Radiation Oncology.

Approaches using a single type of data have been applied to classify human tumors. Here we integrate imaging features and transcriptomic data using a prospectively collected tumor bank. We demonstrate that increased maximum standardized uptake value on pretreatment 18F-fluorodeoxyglucose-positron emission tomography correlates with epithelial-to-mesenchymal transition (EMT) gene expression. We derived and validated 3 major molecular groups, namely squamous epithelial, squamous mesenchymal, and adenocarcinoma, using prospectively collected institutional (n = 67) and publicly available (n = 304) data sets. Patients with tumors of the squamous mesenchymal subtype showed inferior survival outcomes compared with the other 2 molecular groups. High mesenchymal gene expression in cervical cancer cells positively correlated with the capacity to form spheroids and with resistance to radiation. CaSki organoids were radiation-resistant but sensitive to the glycolysis inhibitor, 2-DG. These experiments provide a strategy for response prediction by integrating large data sets, and highlight the potential for metabolic therapy to influence EMT phenotypes in cervical cancer.
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http://dx.doi.org/10.1172/JCI139232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919714PMC
March 2021

Repeatability of F-FDG PET Radiomic Features in Cervical Cancer.

J Nucl Med 2020 Oct 2. Epub 2020 Oct 2.

Mallinckrodt Institute of Radiology, United States.

Knowledge of the intrinsic variability of radiomic features is essential to the proper interpretation of changes in these features over time. The primary aim of this study was to assess the test-retest repeatability of radiomic features extracted from F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) images of cervical tumors. The impact of different image pre-processing methods was also explored. Patients with cervical cancer underwent baseline and repeat FDG PET/CT imaging within 7 days. PET images were reconstructed using 2 methods ordered subset expectation maximization (PETOSEM) or OSEM with point-spread function (PETPSF). Tumors were segmented to produce whole-tumor volumes of interest (VOIWT) and 40% isocontours (VOI40). Voxels were either left at the default size or resampled to 3 mm isotropic voxels. SUV was discretized to a fixed number of bins (32, 64, or 128). Radiomic features were extracted from both VOIs and repeatability was then assessed using Lin's concordance correlation coefficient (CCC). Eleven patients were enrolled and completed the test-retest PET/CT imaging protocol. Shape, neighborhood gray-level difference matrix (NGLDM), and gray-level cooccurence matrix (GLCM) features were repeatable with mean CCC values of 0.81. Radiomic features extracted from PETOSEM images showed significantly better repeatability than features extracted from PETPSF images ( < 0.001). Radiomic features extracted from VOI40 were more repeatable than features extracted from VOIWT ( < 0.001). For most features (78.4%), a change in bin number or voxel size resulted in less than 10% change in feature value. All gray-level emphasis and gray-level run emphasis features showed poor repeatability (CCC values < 0.52) when extracted from VOIWT, but were highly repeatable (mean CCC values > 0.96) when extracted from VOI40. Shape, GLCM, and NGLDM radiomic features were consistently repeatable while gray-level run length matrix (GLRLM) and gray-level zone length matrix (GLZLM) features were highly variable. Radiomic features extracted from 40% isocontours were more repeatable than features extracted from whole-tumor contours. Changes in voxel size or SUV discretization parameters typically resulted in relatively small differences in feature value, though several features were highly sensitive to these changes.
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http://dx.doi.org/10.2967/jnumed.120.247999DOI Listing
October 2020

Early posttherapy clearance of human papillomavirus and treatment response in cervical carcinoma.

Cancer 2020 Sep 8;126(18):4168-4176. Epub 2020 Jul 8.

Washington University Medical Center, St. Louis, Missouri.

Background: Among patients with cervical cancer, little is known about the significance of persistent human papillomavirus (HPV) expression after chemoradiation (CRT). This study evaluated associations between early posttreatment HPV clearance and patient outcomes with an added focus on the value of posttherapy positron emission tomography (PET) imaging.

Methods: Included patients underwent pretreatment testing indicating a high-risk HPV infection and posttreatment testing with a messenger RNA (mRNA)-based genital swab after CRT. Posttherapy responses were stratified on the basis of HPV mRNA detection into an early clearance (EC) group (no mRNA) and a persistent expression (PE) group (detectable mRNA) on the basis of an evaluation at a median of 6 weeks after therapy. The Kaplan-Meier method was used to compare outcomes, and multivariable analysis was used to identify predictors of outcomes.

Results: Seventy-two of the 97 eligible patients (74.2%) had EC. The mean follow-up time was 25 months (range, 4-56 months), and 2-year pelvic control (76.9% vs 50.2%; P = .01) and overall survival (OS; 80.9% vs 52.2%; P < .01) were superior among EC patients. In the multivariable analysis, EC predicted for improved survival (hazard ratio [HR] for mortality, 0.46; 95% confidence interval [CI], 0.21-0.96; P = .047), as did a complete response (CR) on posttherapy PET (HR for less than a CR on PET, 6.17; 95% CI, 2.58-14.72; P < .01). In a subset analysis of patients with a posttherapy PET CR, HPV clearance retained prognostic significance (2-year OS, 95.6% with EC vs 66.7% with PE; P = .04), whereas PE patients without a PET CR had the worst survival (35.9%; P < .01 for trend).

Conclusions: Early posttherapy clearance of HPV is associated with improved survival in cervical cancer. Evaluating HPV expression at this 6-week time point provides prognostic information beyond posttherapy PET imaging and may aid in risk stratification and decisions for treatment escalation.
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http://dx.doi.org/10.1002/cncr.33040DOI Listing
September 2020

Long-term outcomes of intensity-modulated radiation therapy (IMRT) and high dose rate brachytherapy as adjuvant therapy after radical hysterectomy for cervical cancer.

Int J Gynecol Cancer 2020 08 11;30(8):1157-1161. Epub 2020 Jun 11.

Radiation Oncology, Washington University School of Medicine, St Louis, Missouri, USA

Objective: Compared with 3D-planned pelvic radiation, intensity-modulated radiation therapy (IMRT) has been shown to reduce acute toxicity in cervical cancer patients after radical hysterectomy. This study evaluated late toxicity and patterns of failure after post-operative pelvic IMRT interdigitated weekly with high dose rate brachytherapy.

Methods: This retrospective study included 53 cervical cancer patients treated between January 2006 and August 2019 with radical hysterectomy, lymphadenectomy, and post-operative IMRT and high dose rate brachytherapy. The decision to include chemotherapy was made by the treating gynecologic oncologist based on patient-specific criteria including positive pelvic lymph nodes, positive surgical margins, or positive parametrial invasion. The actuarial rates of genitourinary and gastrointestinal toxicity, vaginal cuff/regional nodal/distant failure, and overall survival were calculated using the Kaplan-Meier method.

Results: Median follow-up was 70 months (range 5.4-148) months and age at diagnosis was 47 (range 24-73) years. The 2018 International Federation of Gynecology and Obstetrics (FIGO) clinical stages were IB1 (n=19), IB2 (n=7), IIB (n=7), IIIC1 (n=19), and IIIC2 (n=1). Median radiation dose delivered in 160 cGy daily fractions was 5120 (range 4640-5120) cGy. Median brachytherapy dose prescribed to the vaginal surface delivered in six weekly fractions was 2400 (range 1200-4800) cGy. Concurrent chemotherapy was delivered in 35 (66%) patients. There were no acute grade 3 genitourinary or gastrointestinal toxicities. Late grade 3 occurred in two (3.8%) patients, including a small bowel obstruction and a ureteral stricture. The 5-year actuarial rate for gastrointestinal or genitourinary toxicity was 1.9%. There were no vaginal cuff recurrences. The 5-year actuarial rates for regional nodal failure, distant failure outside the radiation field, any failure, and overall survival were 11%, 11%, 14%, and 85%, respectively.

Conclusions: Post-operative IMRT with high dose rate brachytherapy for patients with cervical cancer is associated with excellent outcomes and limited rates of radiation-related non-hematologic toxicity.
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http://dx.doi.org/10.1136/ijgc-2020-001412DOI Listing
August 2020

Radiologic Assessment of Groin Lymph Nodes in Pelvic Malignancies.

Int J Gynecol Cancer 2020 07 2;30(7):947-953. Epub 2020 Jun 2.

Department of Radiation Oncology, Washington University in Saint Louis, Saint Louis, Missouri, USA

Introduction: Metastatic involvement of groin nodes can alter radiation therapy planning for pelvic tumors. F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) can identify nodal metastases; however, interpretation of PET/CT-positive nodes can be complicated by non-malignant processes. We evaluated quantitative metrics as methods to identify groin metastases in patients with pelvic tumors by comparison with standard subjective interpretive criteria, with pathology as the reference standard.

Methods: We retrospectively identified patients with vulvar, vaginal, or anal cancers who underwent F-FDG PET/CT before pathologic evaluation of groin nodes between 2007 and 2017. Because patho-radiologic correlation was not possible for every node, one index node identified on imaging was selected for each groin. For each index node, standardized uptake value measurements, total lesion glycolysis, metabolic tumor volume, CT-based volume, and short and long axes were measured. Multivariate logistic regression was used to identify metrics predictive for pathologically positive groins and generate a probabilistic model. Area under the receiver-operating characteristic curves (AUCs) for the model were compared with clinical interpretation from the diagnostic report via a Wald's χ test.

Results: Of 55 patients identified for analysis, 75 groins had pathologic evaluation resulting in 75 index groin nodes for analysis with 35 groins pathologically positive for malignancy. Logistic regression identified mean standardized-uptake-value (50% threshold) and short-axis length as the most predictive imaging metrics for metastatic nodal involvement. The probabilistic model performed better at predicting pathologic involvement compared with standard clinical interpretation on analysis (AUC 0.91, 95% CI 0.84 to 0.97 vs 0.80, 95% CI 0.71 to 0.89; p<0.01).

Discussion: Accuracy of F-FDG PET/CT for detecting groin nodal metastases in patients with pelvic tumors may be improved with the use of quantitative metrics. Improving prediction of nodal metastases can aid with appropriate selection of patients for pathologic node evaluation and guide radiation volumes and doses.
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http://dx.doi.org/10.1136/ijgc-2020-001363DOI Listing
July 2020

FIGO 2018 staging criteria for cervical cancer: Impact on stage migration and survival.

Gynecol Oncol 2020 06 2;157(3):639-643. Epub 2020 Apr 2.

Alvin J. Siteman Cancer Center, Washington University in St. Louis School of Medicine, United States of America; Division of Gynecology Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, United States of America.

Objective: To compare FIGO 2009 and FIGO 2018 cervical cancer staging criteria with a focus on stage migration and treatment outcomes.

Methods: This study is based on a database cohort of 1282 patients newly diagnosed with cervical cancer from 1997 to 2019. All underwent standard clinical examination and whole-body FDG-PET. Tumor stage was recorded using the FIGO 2009 system, which excluded surgical pathologic, FDG-PET and other advanced imaging findings, and then re-classified to the FIGO 2018 system, including surgical pathologic and imaging findings. Patient management was based on clinical, surgical, and imaging findings. Stage migration and prognosis were evaluated.

Results: The distribution per the 2009 staging system was stage I in 593 (46%), stage II in 342 (27%), stage III in 263 (21%), and stage IV in 84 (7%) and the 2018 staging system was stage I in 354 (28%), stage II in 156 (12%), stage III in 601 (47%), and stage IV in 171 (13%). No patients were down-staged. Stage migration occurred in 53% (676/1282) and was attributable to detection of occult lymph node metastasis in 520 (41%), occult distant metastasis in 90 (7%), and tumor size and extent in 66 (5%). The 5-year progression-free survivals (PFS) by FIGO 2009 versus FIGO 2018 were as follows: stage I, 80% vs. 87% (p = 0.02); stage II, 59% vs. 71% (p = 0.002); stage III, 35% vs. 55% (p < 0.001), and stage IV, 20% vs. 16% (p = 0.41).

Conclusion: Inclusion of surgical pathologic and imaging findings resulted in upward stage migration in the majority, mostly related to nodal and distant metastasis. While FIGO 2018 improves survival discriminatory ability for stages I and IV patients, survival remains heterogeneous among stage III substages.
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http://dx.doi.org/10.1016/j.ygyno.2020.03.027DOI Listing
June 2020

Treatment Outcome Prediction for Cancer Patients based on Radiomics and Belief Function Theory.

IEEE Trans Radiat Plasma Med Sci 2019 Mar 27;3(2):216-224. Epub 2018 Sep 27.

Department of Radiation Oncology, Washington University, Saint louis, MO 63110 USA.

In this study, we proposed a new radiomics-based treatment outcome prediction model for cancer patients. The prediction model is developed based on belief function theory (BFT) and sparsity learning to address the challenges of redundancy, heterogeneity, and uncertainty of radiomic features, and relatively small-sized and unbalanced training samples. The model first selects the most predictive feature subsets from relatively large amounts of radiomic features extracted from pre- and/or in-treatment positron emission tomography (PET) images and available clinical and demographic features. Then an evidential k-nearest neighbor (EK-NN) classifier is proposed to utilize the selected features for treatment outcome prediction. Twenty-five stage II-III lung, 36 esophagus, 63 stage II-III cervix, and 45 lymphoma cancer patient cases were included in this retrospective study. Performance and robustness of the proposed model were assessed with measures of feature selection stability, outcome prediction accuracy, and receiver operating characteristics (ROC) analysis. Comparison with other methods were conducted to demonstrate the feasibility and superior performance of the proposed model.
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http://dx.doi.org/10.1109/TRPMS.2018.2872406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941853PMC
March 2019

Decreased local immune response and retained HPV gene expression during chemoradiotherapy are associated with treatment resistance and death from cervical cancer.

Int J Cancer 2020 04 4;146(7):2047-2058. Epub 2019 Dec 4.

Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO.

More than one-third of patients with locally advanced cervical cancer do not respond to chemoradiation therapy (CRT). We aimed to characterize the transcriptional landscape of paired human cervical tumors before and during CRT in order to gain insight into the evolution of treatment response and to elucidate mechanisms of treatment resistance. We prospectively collected cervical tumor biopsies from 115 patients both before and 3 weeks into CRT. RNA-sequencing, Gene Set Enrichment Analysis and HPV gene expression were performed on 20 paired samples that had adequate neoplastic tissue mid-treatment. Tumors from patients with no evidence of disease (NED) at last follow-up had enrichment in pathways related to the immune response both pretreatment and mid-treatment, while tumors from patients dead of disease (DOD) demonstrated enrichment in biosynthetic and mitotic pathways but not in immune-related pathways. Patients DOD had decreased expression of T-cell and cytolytic genes and increased expression of PD-L2 mid-treatment compared to patients NED. Histological and immunohistochemical analysis revealed a decrease in tumor-associated lymphocytes (TAL) during CRT in all patients but tumors from patients DOD had a significantly more pronounced decrease in TALs and CD8+ cells mid-treatment, which was validated in a larger mid-treatment cohort. Finally, patients DOD retained more HPV E6/E7 gene expression during CRT and this was associated with increased expression of genes driving mitosis, which was corroborated in vitro. Our results suggest that decreased local immune response and retained HPV gene expression may be acting together to promote treatment resistance during CRT in patients with cervical cancer.
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http://dx.doi.org/10.1002/ijc.32793DOI Listing
April 2020

Molecular Imaging for Radiotherapy Planning and Response Assessment for Cervical Cancer.

Semin Nucl Med 2019 11 19;49(6):493-500. Epub 2019 Jun 19.

Department of Radiation Oncology, Barnes-Jewish Hospital, St. Louis, MO; Washington University School of Medicine, St. Louis, MO. Electronic address:

Positron emission tomography (PET) with [F]fluorodeoxyglucose (FDG) leverages imaging contrast from accelerated and aberrant glucose metabolism, which is a hallmark of cancer. FDG-PET is essential for assessing involved lymph nodes and distant metastases for cervical cancer. It is also utilized for target delineation in radiation treatment planning, with investigations into functional bone marrow sparing intensity modulated radiation therapy. Tumor heterogeneity in FDG-uptake is part of a radiomics approach to potentially escalate treatment to radiation-resistant tumors. Standardizing posttreatment PET surveillance could also allow early surgical salvage of recurrent tumors. The future of molecular imaging in cervical cancer will require development of novel PET tracers to personalize treatments based on tumor biology.
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http://dx.doi.org/10.1053/j.semnuclmed.2019.06.009DOI Listing
November 2019

Impact of tumor histology on detection of pelvic and para-aortic nodal metastasis with F-fluorodeoxyglucose-positron emission tomography in stage IB cervical cancer.

Int J Gynecol Cancer 2019 11 30;29(9):1351-1354. Epub 2019 Aug 30.

Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri, USA

Objective: F-fluorodeoxyglucose-positron emission tomography (FDG-PET) detection of metastatic nodal disease is useful for guiding cervical cancer treatment but the impact of tumor histology is unknown. This study reports the detection of FDG avid pelvic and para-aortic lymph nodes in patients with early stage cervical cancer with squamous carcinoma and adenocarcinoma tumor histology.

Methods: Patients with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB1-2 cervical cancer who underwent pre-surgical FDG-PET between March 1999 and February 2018 were identified in a tertiary academic center database. All patients had radical hysterectomy with pelvic and para-aortic lymph node dissection. Detection of pelvic and para-aortic lymph nodes by FDG-PET versus surgical dissection was compared. FDG-PET sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined and stratified by tumor histology.

Results: We identified 212 patients with early stage cervical cancer (84% FIGO IB1, 16% IB2) who underwent pre-surgical FDG-PET; 137 (65%) patients had squamous carcinoma and 75 (35%) patients had adenocarcinoma. PET/computed tomography was performed in 189 (89%) patients and 23 (11%) had PET only. Surgical dissection revealed positive pelvic and para-aortic lymph nodes in 25% and 3.3% of patients, respectively. For squamous carcinoma, sensitivity, specificity, PPV, and NPV of FDG-PET for pelvic nodal metastasis were 44%, 99%, 95%, and 78%, respectively. For adenocarcinoma, the corresponding results for pelvic nodal metastasis were 25%, 99%, 67%, and 92%, respectively. The overall values for sensitivity, specificity, PPV, and NPV of FDG-PET for para-aortic nodal metastasis were 29%, 99%, 67%, and 98%, respectively.

Discussion: Pelvic nodal metastasis was less likely to be detected by FDG-PET in patients with early stage adenocarcinoma than with squamous carcinoma.
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http://dx.doi.org/10.1136/ijgc-2019-000528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6984174PMC
November 2019

Concurrent chemoradiation for cervical cancer: Comparison of LDR and HDR brachytherapy.

Brachytherapy 2019 May - Jun;18(3):353-360. Epub 2019 Apr 7.

Mallinckrodt Institute of Radiology, St. Louis, MO. Electronic address:

Purpose: To compare clinical outcomes between low-dose-rate (LDR) brachytherapy and high-dose-rate (HDR) brachytherapy for cervical cancer patients.

Methods And Materials: All consecutive newly diagnosed cervical cancer patients undergoing pretreatment 18-fluorodeoxyglucose positron emission tomography imaging and treated with curative-intent definitive chemoradiation from 1997 to 2016 at a U.S. academic center were included. Brachytherapy boost was LDR or HDR 2D treatment planning from 1997 to 2005 and HDR with MR-based 3D planning from 2005 to 2016. Local control (LC), cancer-specific survival (CSS), and late bowel/bladder complications were evaluated.

Results: Tumor stages were International Federation of Gynecology and Obstetrics IB1-IIB (n = 457; 75%) and III-IVA (n = 152; 25%). Brachytherapy was LDR for 104 patients and HDR for 505 patients. Concurrent weekly cisplatin was administered to 536 patients (88%). With median followup of 9.4 years, there was no difference in LC (p = 0.24) or CSS (p = 0.50) between LDR and HDR brachytherapy. Cox multivariable regression showed that only International Federation of Gynecology and Obstetrics stage III-IVA (HR=2.4, p = 0.004) was associated with worse LC. A propensity-matched cohort (90 LDR vs. 90 HDR) was created, and the 5-year LC rates were 88% LDR and 82% HDR, p = 0.26; 5-year CSS rates were 66% LDR and 58% HDR, p = 0.19; 5-year grade ≥3 bowel/bladder toxicities were 23% LDR and 16% HDR, p = 0.44. For all patients, the 5-year late toxicity in stage III-IVA patients was higher with LDR 47% vs. HDR 15%, p = 0.03, with no difference in LC, 86% and 75%, respectively (p = 0.09).

Conclusions: There was no difference in LC with either LDR or HDR brachytherapy. The late complication rate was reduced with HDR and 3D-planned brachytherapy compared to LDR and 2D-planned brachytherapy.
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http://dx.doi.org/10.1016/j.brachy.2018.11.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477730PMC
December 2019

Clinical outcomes after isolated pelvic failure in cervical cancer patients treated with definitive radiation.

Gynecol Oncol 2019 06 21;153(3):530-534. Epub 2019 Mar 21.

Department of Radiation Oncology, Washington University School of Medicine, United States of America. Electronic address:

Purpose: To describe clinical outcomes in patients with isolated pelvic failures after definitive radiation treatment for cervical cancer.

Methods And Materials: Cervical cancer patients with isolated pelvic failure after definitive radiation with brachytherapy boost were identified in a tertiary academic center database from 1997 to 2016. All patients received an FDG-PET scan prior to their initial treatment and at the time of their first recurrence. Isolated failures in the cervix or pelvic nodes were biopsy-proven. Distant failure and overall survival (OS) were censored outcomes.

Results: Isolated pelvic failure was detected in 67(11%) out of 607 consecutive patients treated with external beam pelvic radiation and brachytherapy boost. The median time to isolated pelvic recurrence was 9 months (range 3-198). Median follow-up time for patients alive after isolated pelvic recurrence was 40 months (range 0.6-183). Of these 67 patients, 28(42%) received salvage surgery, 17(25%) received chemotherapy alone, and 22(33%) received neither surgery nor chemotherapy. The median time to distant failure after isolated pelvic failure was 20 months (95% CI 3-37), with no significant difference between patients treated surgically vs. non-surgically. FDG-avid pelvic and para-aortic nodes at initial presentation were associated with worse distant control after isolated pelvic failure (HR = 3.4, 95% CI 1.0-12). Median OS for patients treated with surgery, chemotherapy alone, and neither surgery nor chemotherapy was 29 months (95% CI 16-41), 12 months (95% CI 3-21), and 3 months (95% CI 1-5), respectively.

Conclusions: Patients who have pelvic and para-aortic nodal disease at initial presentation are at higher risk of failing distantly after isolated pelvic failure, which should be considered when counseling patients on aggressive surgical salvage. Surgical salvage was associated with prolonged survival after isolated pelvic failure.
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http://dx.doi.org/10.1016/j.ygyno.2019.03.104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428083PMC
June 2019

Measurement Repeatability of F-FDG PET/CT Versus F-FDG PET/MRI in Solid Tumors of the Pelvis.

J Nucl Med 2019 08 7;60(8):1080-1086. Epub 2019 Feb 7.

Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri.

Knowledge of the within-subject variability of F-FDG PET/MRI measurements is necessary for proper interpretation of quantitative PET or MRI metrics in the context of therapeutic efficacy assessments with integrated PET/MRI scanners. The goal of this study was to determine the test-retest repeatability of these metrics on PET/MRI, with comparison to similar metrics acquired by PET/CT. This prospective study enrolled subjects with pathology-proven pelvic malignancies. Baseline imaging consisted of PET/CT immediately followed by PET/MRI, using a single 370-MBq F-FDG dose. Repeat imaging was performed within 7 d using an identical imaging protocol, with no oncologic therapy between sessions. PET imaging on both scanners consisted of a list-mode acquisition at a single pelvic station. The MRI consisted of 2-point Dixon imaging for attenuation correction, standard sequences for anatomic correlation, and diffusion-weighted imaging. PET data were statically reconstructed using various frame durations and minimizing uptake time differences between sessions. SUV metrics were extracted for both PET/CT and PET/MRI in each imaging session. Apparent diffusion coefficient (ADC) metrics were extracted for both PET/MRI sessions. The study cohort consisted of 14 subjects (13 female, 1 male) with various pelvic cancers (11 cervical, 2 rectal, 1 endometrial). For SUV, the within-subject coefficient of variation (wCV) appeared higher for PET/CT (8.5%-12.8%) than PET/MRI (6.6%-8.7%) across all PET reconstructions, though with no significant repeatability differences (all values ≥ 0.08) between modalities. For lean body mass-adjusted SUV, the wCVs appeared similar for PET/CT (9.9%-11.5%) and PET/MRI (9.2%-11.3%) across all PET reconstructions, again with no significant repeatability differences (all values ≥ 0.14) between modalities. For PET/MRI, the wCV for ADC of 3.5% appeared lower than the wCVs for SUV (6.6%-8.7%) and SUL (9.2%-11.3%), though without significant repeatability differences (all values ≥ 0.23). For solid tumors of the pelvis, the repeatability of the evaluated SUV and ADC metrics on F-FDG PET/MRI is both acceptably high and similar to previously published values for F-FDG PET/CT and MRI, supporting the use of F-FDG PET/MRI for quantitative oncologic treatment response assessments.
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http://dx.doi.org/10.2967/jnumed.118.218735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6681694PMC
August 2019

Intensity Modulated Radiation Therapy and Image-Guided Adapted Brachytherapy for Cervix Cancer.

Int J Radiat Oncol Biol Phys 2019 04 14;103(5):1088-1097. Epub 2018 Nov 14.

Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri; Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Missouri. Electronic address:

Purpose: This study reported long-term outcomes of patients with cervical cancer who were treated with intensity modulated radiation therapy and 3-dimensional (3D) image-guided adapted brachytherapy (IMRT/3D-IGABT) compared with those treated with 2-dimensional (2D) external irradiation and 2D brachytherapy (2D EBRT/BT).

Methods And Materials: This study included patients with newly diagnosed cervical cancer and pretreatment fluorodeoxyglucose positron emission tomography scans who were treated with curative-intent irradiation from 1997 to 2013. The treatment policy changed from using 2D EBRT/BT to IMRT/3D-IGABT in 2005. Patterns of recurrence, cancer-specific survival (CSS), and overall survival (OS) were evaluated. Late gastrointestinal and genitourinary toxicity were scored with National Cancer Institute Common Terminology Criteria for Adverse Events.

Results: The median follow-up for patients alive at the time of last follow-up in the 2D EBRT/BT group (n = 300) was 15.3 years (range, 10.8-20.5 years). In the IMRT/3D-IGABT group (n = 300), it was 7 years (range, 5-12.4 years). According to the International Federation of Gynecology and Obstetrics, 33% of tumors were stage IB1 to IB2, 41% were stage IIA to IIB, and 26% were stage IIIA to IVA. The results after 5 years for patients treated with 2D EBRT/BT showed that freedom from relapse (FFR) was 57%, CSS was 62%, and OS was 57%. For the IMRT/3D-IGABT group, the 5-year results showed that FFR was 65% (P = .04), CSS was 69% (P = .01), and OS was 61% (P = .04). When stratified by lymph node status according to positron emission tomography scan results, disease control was most improved with IMRT/3D-IGABT versus 2D EBRT/BT in patients with positive pelvic lymph nodes only (P = .02). Cumulatively, 88 of 600 patients (15%) had grade ≥3 late bowel/bladder toxicity. The 2D EBRT/BT group had 55 patients (18%), and the IMRT/3D-IGABT group had 33 patients (11%; P = .02).

Conclusions: IMRT/3D-IGABT was associated with improved survival and decreased gastrointestinal and genitourinary toxicity in patients with cervical cancer compared with those who received 2D EBRT/BT.
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http://dx.doi.org/10.1016/j.ijrobp.2018.11.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065668PMC
April 2019

Long-term outcomes of follicular variant vs classic papillary thyroid carcinoma.

Endocr Connect 2018 Dec;7(12):1226-1235

Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.

The majority of papillary thyroid carcinoma (PTC) cases comprise classic papillary (C-PTC) and follicular variant (FV-PTC) histologic sub-types. Historically, clinical equivalency was assumed, but recent data suggest C-PTC may have poorer outcomes. However, large single-institution series with long-term outcomes of C-PTC and FV-PTC, using modern pathologic criteria for FV-PTC, are needed. Our objective was to compare prevalence and impact of clinicopathologic factors, including BRAF mutation status, on long-term outcomes of C-PTC and FV-PTC. We hypothesized that patients with C-PTC would have higher risk disease features and worse survival outcomes. This retrospective study included 1293 patients treated at a single, US academic institution between 1943 and 2009 with mean follow-up of 8.6 years. All patients underwent either partial or total thyroidectomy and had invasive C-PTC or FV-PTC per modern pathology criteria. Primary study measurements included differences in recurrence-free survival (RFS), disease-specific survival (DSS) and associations with clinicopathologic factors including the BRAF mutation. Compared to FV-PTC, C-PTC was associated with multiple features of high-risk disease (P < 0.05) and significantly reduced RFS and DSS. Survival differences were consistent across univariate, multivariate and Kaplan-Meier analyses. BRAF mutations were more common in C-PTC (P = 0.002). However, on Kaplan-Meier analysis, mutational status did not significantly impact RFS or DSS for patients with either histologic sub-type. C-PTC therefore indicates higher-risk disease and predicts for significantly poorer long-term outcomes when compared to FV-PTC. The nature of this difference in outcome is not explained by traditional histopathologic findings or by the BRAF mutation.
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http://dx.doi.org/10.1530/EC-18-0264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240143PMC
December 2018

Spatial relationship of 2-deoxy-2-[F]-fluoro-D-glucose positron emission tomography and magnetic resonance diffusion imaging metrics in cervical cancer.

EJNMMI Res 2018 Jun 15;8(1):52. Epub 2018 Jun 15.

Department of Radiation Oncology, Washington University School of Medicine, 660 S. Euclid Ave, Box 8224, St. Louis, MO, 63110, USA.

Background: This study investigated the spatial relationship of 2-deoxy-2-[F]-fluoro-D-glucose positron emission tomography ([F]FDG-PET) standardized uptake values (SUVs) and apparent diffusion coefficients (ADCs) derived from magnetic resonance (MR) diffusion imaging on a voxel level using simultaneously acquired PET/MR data. We performed an institutional retrospective analysis of patients with newly diagnosed cervical cancer who received a pre-treatment simultaneously acquired [F]FDG-PET/MR. Voxel SUV and ADC values, and global tumor metrics including maximum SUV (SUV), mean ADC (ADC), and mean tumor-to-muscle ADC ratio (ADC) were compared. The impacts of histology, grade, and tumor volume on the voxel SUV to ADC relationship were also evaluated. The potential prognostic value of the voxel SUV/ADC relationship was evaluated in an exploratory analysis using Kaplan-Meier/log-rank and univariate Cox analysis.

Results: Seventeen patients with PET/MR scans were identified. There was a significant inverse correlation between SUV and ADC, and SUV and ADC. In the voxelwise analysis, squamous cell carcinomas (SCCAs) and poorly differentiated tumors showed a consistent significant inverse correlation between voxel SUV and ADC values; adenocarcinomas (AdenoCAs) and well/moderately differentiated tumors did not. The strength of the voxel SUV/ADC correlation varied with metabolic tumor volume (MTV). On log-rank analysis, the correlation between voxel SUV/ADC values was prognostic of disease-free survival (DFS).

Conclusions: In this hypothesis-generating study, a consistent inverse correlation between voxel SUV and ADC values was seen in SCCAs and poorly differentiated tumors. On univariate statistical analysis, correlation between voxel SUV and ADC values was prognostic for DFS.
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http://dx.doi.org/10.1186/s13550-018-0403-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003894PMC
June 2018

The Role of PET Imaging in Gynecologic Radiation Oncology.

PET Clin 2018 Apr;13(2):225-237

Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO 63110, USA. Electronic address:

The goal of this review is to discuss the current utility of fluorine-18-fluorodeoxyglucose (FDG)-PET for radiation oncologists who treat gynecologic malignancies. FDG-PET/computed tomography (CT) is recommended for baseline assessment in cervical cancer and for staging in vulvar and vaginal cancer. The authors use FDG-PET/CT in definitive radiation treatment planning for cervical, vulvar, and vaginal cancer. PET may be helpful for salvage radiation treatment planning for any recurrent gynecologic malignancy. There are published data to support the use of PET in posttreatment evaluation of cervical and vulvar cancer.
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http://dx.doi.org/10.1016/j.cpet.2017.11.007DOI Listing
April 2018

Magnetic resonance imaging metal artifact reduction for eye plaque patient with dental braces.

J Contemp Brachytherapy 2017 Oct 30;9(5):490-495. Epub 2017 Oct 30.

Department of Radiation Oncology.

Purpose: To determine if metal artifact reduction can minimize magnetic susceptibility artifacts in the orbits for an eye plaque brachytherapy patient with metallic dental braces.

Material And Methods: A 62-year-old female patient with a choroidal melanoma in the right eye received a 1.5 T magnetic resonance imaging (MRI) simulation for 3D eye plaque brachytherapy planning. The protocol included conventional 3D T-weighted and 2D T-weighted MRIs. A vendor-supplied T-weighted metal artifact reduction sequence was added to the protocol to reduce magnetic susceptibility artifacts from the metallic dental braces. The metal artifact reduction sequence combined turbo spin echo acquisitions, high RF excitation and readout bandwidths, and view angle tilting and slice encoding for metal artifact correction with z-shimming to correct in-plane and through-plane image distortions, respectively.

Results: Dental braces caused significant signal loss and image distortion in the orbits on the conventional T-weighted and T-weighted MRIs, and the MRIs were unusable for treatment planning. The metal artifact reduction sequence with 13 z-phase encodes minimized distortion and signal loss in the orbits, allowing the tumor to be clearly delineated.

Conclusions: T-weighted MRI with metal artifact reduction was successfully applied to minimize artifacts in the orbits resulting from the dental braces, thus allowing the MRIs to be used in 3D brachytherapy treatment planning.
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http://dx.doi.org/10.5114/jcb.2017.71184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705839PMC
October 2017

Serum squamous cell carcinoma antigen as an early indicator of response during therapy of cervical cancer.

Br J Cancer 2018 01 7;118(1):72-78. Epub 2017 Nov 7.

Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO 63110, USA.

Background: Pretreatment serum squamous cell carcinoma antigen (SCCA) is a prognostic biomarker in women with cervical cancer. SCCA has not been evaluated as an early indicator of response to chemoradiation therapy (CRT). The molecular role of the two SCCA isoforms, SCCA1 (SERPINB3) and SCCA2 (SERPINB4), in cervical cancer is unknown. We hypothesised that changes in serum SCCA during definitive CRT predicts treatment response, and that SCCA1 mediates radiation resistance.

Methods: Patients treated with definitive CRT for cervical squamous carcinoma with serum SCCA measured were included. SCCA immunohistochemistry was performed on tumour biopsies. Post-treatment FDG-PET/CT, recurrence, and overall survival were recorded. Radiation response of cervical tumour cell lines after SCCA1 expression or CRISPR/Cas9 knockout was evaluated by clonogenic survival assay.

Results: Persistently elevated serum SCCA during definitive CRT was an independent predictor of positive post-therapy FDG-PET/CT (P=0.043), recurrence (P=0.0046) and death (P=0.015). An SCCA1-expressing vector increased radioresistance, while SCCA knock out increased radiosensitivity of cervical tumour cell lines in vitro.

Conclusions: Early response assessment with serum SCCA is a powerful prognostic tool. These findings suggest that escalation of therapy in patients with elevated or sustained serum SCCA and molecular targeting of SCCA1 should be considered.
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http://dx.doi.org/10.1038/bjc.2017.390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765231PMC
January 2018

MRI-based treatment planning and dose delivery verification for intraocular melanoma brachytherapy.

Brachytherapy 2018 Jan - Feb;17(1):31-39. Epub 2017 Aug 14.

Department of Radiation Oncology, Washington University School of Medicine, Saint Louis, MO.

Purpose: Episcleral plaque brachytherapy (EPB) planning is conventionally based on approximations of the implant geometry with no volumetric imaging following plaque implantation. We have developed an MRI-based technique for EPB treatment planning and dose delivery verification based on the actual patient-specific geometry.

Methods And Materials: MR images of 6 patients, prescribed 85 Gy over 96 hours from Collaborative Ocular Melanoma Study-based EPB, were acquired before and after implantation. Preimplant and postimplant scans were used to generate "preplans" and "postplans", respectively. In the preplans, a digital plaque model was positioned relative to the tumor, sclera, and nerve. In the postplans, the same plaque model was positioned based on the imaged plaque. Plaque position, point doses, percentage of tumor volume receiving 85 Gy (V), and dose to 100% of tumor volume (D) were compared between preplans and postplans. All isodose plans were computed using TG-43 formalism with no heterogeneity corrections.

Results: Shifts and tilts of the plaque ranged from 1.4 to 8.6 mm and 1.0 to 3.8 mm, respectively. V was ≥97% for 4 patients. D for preplans and postplans ranged from 83 to 118 Gy and 45 to 110 Gy, respectively. Point doses for tumor apex and base were all found to decrease from the preimplant to the postimplant plan, with mean differences of 16.7 ± 8.6% and 30.5 ± 11.3%, respectively.

Conclusions: By implementing MRI for EPB, we eliminate reliance on approximations of the eye and tumor shape and the assumption of idealized plaque placement. With MRI, one can perform preimplant as well as postimplant imaging, facilitating EPB treatment planning based on the actual patient-specific geometry and dose-delivery verification based on the imaged plaque position.
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http://dx.doi.org/10.1016/j.brachy.2017.07.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366337PMC
July 2018

Intensity modulated radiation therapy for squamous cell carcinoma of the vulva: Treatment technique and outcomes.

Adv Radiat Oncol 2017 Apr-Jun;2(2):148-158. Epub 2017 Feb 28.

Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.

Objective: The objective of this study was to present the treatment technique and evaluate clinical outcomes after intensity modulated radiation therapy (IMRT) for vulvar cancer.

Methods And Materials: This retrospective study included 39 patients with squamous cell carcinoma of the vulva treated with IMRT from 2005 to 2015. There were 21 patients treated with postoperative IMRT, 13 with definitive IMRT, and 5 with preoperative IMRT. Tumor staging was Federation of Gynecology and Obstetrics stage I in 6, stage II in 7, stage III in 19, and stage IV in 7 patients. Concurrent chemotherapy was administered to 14 patients. Brachytherapy was delivered in 8 patients.

Results: The median follow-up was 34 months (range, 3.3-71). Median IMRT dose to patients receiving pre- or postoperative IMRT was 5040 cGy (range, 5040-6080). Median combined IMRT and brachytherapy dose to gross tumor was 7000 cGy (range, 5040-7520) in those treated with definitive RT. The 3-year locoregional control (LRC) and overall survival for those receiving postoperative RT were 89% and 67%, respectively. The 3-year LRC and overall survival for those receiving definitive IMRT were 42% and 49%, respectively. In patients receiving definitive or neoadjuvant IMRT, 69% had complete clinical response and 44% had complete pathologic response. The actuarial 3-year inguinal recurrence rate was 7%. There were no acute grade 3-4 hematological, gastrointestinal, or genitourinary toxicities. There were no late grade 3-4 gastrointestinal or genitourinary toxicities.

Conclusions: IMRT for vulvar cancer is associated with high rates of LRC in the postoperative setting and limited radiation-related toxicity. Durable LRC of disease after definitive IMRT remains challenging, and several refinements to our treatment technique are suggested.
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http://dx.doi.org/10.1016/j.adro.2017.02.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514255PMC
February 2017

Improved survival with definitive chemoradiation compared to definitive radiation alone in squamous cell carcinoma of the vulva: A review of the National Cancer Database.

Gynecol Oncol 2017 09 27;146(3):572-579. Epub 2017 Jun 27.

Department of Radiation Oncology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, United States. Electronic address:

Background: It is unclear whether definitive chemoradiation (CRT) results in improved overall survival compared to radiation therapy (RT) alone in patients with vulvar cancer who are not candidates for surgery. We compared these treatment strategies in the National Cancer Database (NCDB).

Methods: We identified 1352 patients with pathologically-confirmed squamous cell carcinoma of the vulva treated with definitive RT (n=353) or definitive CRT (n=999) between 2003 and 2014 in the NCDB. Exclusion criteria were metastatic disease at diagnosis, RT dose <4000cGy, follow-up <6months, and surgical treatment. Overall survival was compared using Kaplan-Meier method with log-rank test. Cox proportional hazard modeling, propensity score matching, and subgroup analyses were performed.

Results: The median age overall was 66 (23-90) years. The CRT group was younger (p<0.001) and had more advanced FIGO staging (p<0.001) compared to the RT group. Median radiation dose was 5940 (4000-7920) cGy. The median follow-up for living patients was longer in the CRT group (45.2months [6.0-131.6]) than RT (34.4months [6.1-127.6]) (p=0.004). The 5-year overall survival was higher in the CRT group compared to RT (49.9% vs. 27.4%, p<0.001). On multivariate analysis, CRT was associated with a reduced hazard of death compared to RT (HR: 0.76 [0.63-0.91], p=0.003). The effect remained significant after propensity score matching (HR: 0.78 [0.63-0.97], p=0.023). On subgroup analysis, patients with FIGO stage I only had a trend towards improved survival with CRT (p=0.058).

Conclusions: In the NCDB, definitive chemoradiation was associated with higher overall survival compared to radiation alone in patients with squamous cell carcinoma of the vulva who did not receive surgery. These findings suggest that concurrent chemoradiation may be beneficial for select patients in the definitive setting.
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http://dx.doi.org/10.1016/j.ygyno.2017.06.022DOI Listing
September 2017

Which patients with inoperable vulvar cancer may benefit from brachytherapy in addition to external beam radiation? A Surveillance, Epidemiology, and End Results analysis.

Brachytherapy 2017 Jul - Aug;16(4):831-840. Epub 2017 May 19.

Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO. Electronic address:

Purpose: It is unknown whether brachytherapy after external beam radiation (EBRT + BT) results in improved outcomes compared with EBRT alone for patients with inoperable vulvar cancer. The purpose of this study was to compare survival outcomes for patients who received these treatment modalities.

Methods And Materials: Data between 1973 and 2011 from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database were analyzed. Patients with Federation of International Gynecologists and Obstetricians stage I-IVA vulvar cancer treated with definitive EBRT + BT or EBRT alone were included. Patients with prior surgical resection were excluded. Disease-specific survival (DSS) and overall survival were compared using the Kaplan-Meier method and Cox proportional hazard models.

Results: A total of 649 patients were analyzed, of which 617 received EBRT alone and 32 received EBRT + BT. Median follow-up was 33 months in surviving patients. The use of brachytherapy declined from 16% of cases treated in 1973-1980 to 4% in 2001-2011 (p = 0.04). EBRT + BT vs. EBRT alone was not significantly associated with improved DSS (45% vs. 33% at 5 years) or overall survival (34% vs. 24% at 5 years) on univariate or multivariate analyses. On post hoc subgroup analyses, brachytherapy consolidation was associated with higher 5-year DSS in a composite subgroup that included patients with stage IVA disease, tumor >4 cm, or node-positive disease (52% vs. 27%, p = 0.02).

Conclusions: Utilization of BT consolidation with EBRT for vulvar cancer is declining in the United States. EBRT + BT is not associated with improved survival compared with EBRT alone in the overall group of patients. Certain subgroups of patients might benefit from brachytherapy, but this hypothesis requires validation in future studies.
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http://dx.doi.org/10.1016/j.brachy.2017.03.012DOI Listing
May 2017

Survival of Cervical Cancer Patients Presenting with Occult Supraclavicular Metastases Detected by FDG-Positron Emission Tomography/CT: Impact of Disease Extent and Treatment.

Gynecol Obstet Invest 2018 8;83(1):83-89. Epub 2017 Apr 8.

Department of Gynecology and Obstetrics, Loma Linda University School of Medicine, Loma Linda, CA, USA.

Aims: The study aimed to do the following: (1) describe progression free survival (PFS) and overall survival (OS) of women with cervical cancer presenting with occult supraclavicular lymph node (SCLN) metastases, identified by positron emission tomography CT (PET-CT) and (2) compare OS of patients with isolated SCLN metastases to that of patients with SCLN and extranodal metastatic disease.

Methods: Patients were identified retrospectively. Treatment intent was abstracted. PFS and OS in the high-dose chemo-radiotherapy (RT), palliative RT, and supportive treatment groups, as well as OS of patients with SCLN metastases only vs. SCLN and extranodal metastases were calculated.

Results: Fourteen patients received high-dose chemo-RT, 32 received palliative RT, and 6 received supportive care (n = 52). Median PFS was 3 months in high-dose chemo-RT group and 1 month in palliative RT (p = ns). Median OS was 12 months in high-dose chemo-RT group, 7 months in palliative RT group, and 2 months in palliative care group (p = 0.05). OS was significantly different between patients with isolated SCLN disease vs. SCLN and extranodal disease, that is, 10.5 vs. 3 months (p = 0.009, χ2 = 6.9).

Conclusions: In this limited analysis, median OS of cervical cancer patients with PET/CT-positive SCLN metastases was the longest when treated with high-dose chemo-RT. Patients with SCLN and extranodal metastases experienced significantly shorter OS, as compared to patients with SCLN only disease.
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http://dx.doi.org/10.1159/000458706DOI Listing
July 2018

Metal artifact reduction in MRI-based cervical cancer intracavitary brachytherapy.

Phys Med Biol 2017 04 17;62(8):3011-3024. Epub 2017 Mar 17.

Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63110, United States of America.

Magnetic resonance imaging (MRI) plays an increasingly important role in brachytherapy planning for cervical cancer. Yet, metal tandem, ovoid intracavitary applicators, and fiducial markers used in brachytherapy cause magnetic susceptibility artifacts in standard MRI. These artifacts may impact the accuracy of brachytherapy treatment and the evaluation of tumor response by misrepresenting the size and location of the metal implant, and distorting the surrounding anatomy and tissue. Metal artifact reduction sequences (MARS) with high bandwidth RF selective excitations and turbo spin-echo readouts were developed for MRI of orthopedic implants. In this study, metal artifact reduction was applied to brachytherapy of cervical cancer using the orthopedic metal artifact reduction (O-MAR) sequence. O-MAR combined MARS features with view angle tilting and slice encoding for metal artifact correction (SEMAC) to minimize in-plane and through-plane susceptibility artifacts. O-MAR improved visualization of the tandem tip on T and proton density weighted (PDW) imaging in phantoms and accurately represented the diameter of the tandem. In a pilot group of cervical cancer patients (N  =  7), O-MAR significantly minimized the blooming artifact at the tip of the tandem in PDW MRI. There was no significant difference observed in artifact reduction between the weak (5 kHz, 7 z-phase encodes) and medium (10 kHz, 13 z-phase encodes) SEMAC settings. However, the weak setting allowed a significantly shorter acquisition time than the medium setting. O-MAR also reduced susceptibility artifacts associated with metal fiducial markers so that they appeared on MRI at their true dimensions.
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http://dx.doi.org/10.1088/1361-6560/62/8/3011DOI Listing
April 2017

Association of post-treatment positron emission tomography with locoregional control and survival after radiation therapy for squamous cell carcinoma of the vulva.

Radiother Oncol 2017 03 4;122(3):445-451. Epub 2017 Jan 4.

Department of Radiation Oncology, Washington University School of Medicine, St. Louis, United States; Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, United States. Electronic address:

Background/purpose: The aim of this study was to investigate the use of post-treatment F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for vulvar cancer and compare metabolic response to clinical outcomes.

Materials/methods: This retrospective study included 21 patients with vulvar squamous cell carcinoma treated with curative-intent radiation between 2007 and 2015. All patients received intensity-modulated radiation treatment (IMRT), a pre-treatment FDG/PET-CT, and a post-treatment FDG-PET/CT performed at a median time of 3months post-IMRT.

Results: Median follow-up time was 28months. Post-treatment FDG-PET/CT demonstrated no evidence of disease (NED) in 12 patients and residual or progressive disease (PD) in 9. FDG-PET/CT response significantly correlated with biopsy-proven locoregional failure (p=0.02) and was the only significant factor associated with overall survival (OS) (p=0.049). Patients with NED on FDG-PET had a 2-year locoregional control (LRC) of 89% versus 25% for those with PD (p<0.01). Patients with NED on FDG-PET/CT had a 2-year OS of 100% versus 42% for those with PD (p=0.02). FDG-PET/CT evaluation had a sensitivity of 100% and a specificity of 71% for detecting pathologically proven residual disease in patients receiving neoadjuvant or definitive radiation.

Conclusion: In this single-institution study of women with vulvar cancer, post-treatment response on FDG-PET/CT was associated with LRC and OS.
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http://dx.doi.org/10.1016/j.radonc.2016.12.019DOI Listing
March 2017

Efficacy and toxicity of rectal cancer reirradiation using IMRT for patients who have received prior pelvic radiation therapy.

Adv Radiat Oncol 2016 Apr-Jun;1(2):94-100. Epub 2016 Feb 22.

Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado.

Purpose: Locally recurrent rectal cancer may cause significant morbidity. Prior reports of rectal cancer reirradiation following local recurrence suggest treatment efficacy, with variable rates of late toxicity. Modern techniques including intensity modulated radiation therapy (IMRT) may improve the therapeutic index. We report outcomes for pelvic reirradiation as treatment for rectal cancer using IMRT.

Methods And Materials: The records of 31 patients undergoing reirradiation for rectal cancer between 2004 and 2013 were reviewed. All patients underwent IMRT using an accelerated hyperfractionation (39 Gy in 1.5-Gy fractions delivered twice daily, n=15) or once-daily fractionation technique (median dose, 30.4 Gy; range, 27-40 Gy in 15-22 fractions; n = 16). The median cumulative dose was 77 Gy (range, 59-113), and the median interval from prior pelvic radiation therapy was 39.8 months (range, 10.1-307.6). Treatment intent was palliative in 20 patients and neoadjuvant or adjuvant in 11 patients. Surgery was generally reserved for patients with an isolated local recurrence. Concurrent chemotherapy was administered for 25/31 patients, most frequently capecitabine (n=11) or continuous infusion 5-fluorouracil (n=10).

Results: Median follow-up was 11.3 months. The prescribed treatment was completed in 29/31 patients (93.5%). Among 18 patients with symptoms attributable to recurrent disease, successful palliation was achieved in 10/18 (55.6%). The rate of grade 2 and grade 3 acute toxicities was 32.3% and 3.2%, respectively. Local control rates at 1 and 2 years were 61.3% and 47.3%, respectively. Median overall survival was 21.9 months, and 1-year survival was 66.7% for patients who had surgical resection versus 58.7% for those who did not ( = .0802).

Conclusions: Rectal cancer reirradiation using IMRT is well-tolerated in the setting of prior pelvic radiation therapy. Given significant risk of local progression, further dose escalation may be warranted for patients with life expectancy exceeding 1 year.
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http://dx.doi.org/10.1016/j.adro.2016.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5506712PMC
February 2016

Clinical implementation of multisequence MRI-based adaptive intracavitary brachytherapy for cervix cancer.

J Appl Clin Med Phys 2016 01 8;17(1):121-131. Epub 2016 Jan 8.

Washington University School of Medicine.

The purpose of this study was to describe the clinical implementation of a magnetic resonance image (MRI)-based approach for adaptive intracavitary brachytherapy (ICBT) of cervix cancer patients. Patients were implanted with titanium tandem and colpostats. MR imaging was performed on a 1.5-T Philips scanner using T2-weighted (T2W), proton-density weighted (PDW), and diffusion-weighted (DW) imaging sequences. Apparent diffusion coefficient (ADC) maps were generated from the DW images. All images were fused. T2W images were used for the definition of organs at risk (OARs) and dose points. ADC maps in conjunction with T2W images were used for target delineation. PDW images were used for applicator definition. Forward treatment planning was performed using standard source distribution rules normalized to Point A. Point doses and dose-volume parameters for the tumor and OARs were exported to an automated dose-tracking application. Brachytherapy doses were adapted for tumor shrinkage and OAR variations during the course of therapy. The MRI-based ICBT approach described here has been clinically implemented and is carried out for each brachytherapy fraction. Total procedure time from patient preparation to delivery of treatment is typically 2 hrs. Implementation of our tech-nique for structure delineation, applicator definition, dose tracking, and adaptation is demonstrated using treated patient examples. Based on published recommendations and our clinical experience in the radiation treatment of cervix cancer patients, we have refined our standard approach to ICBT by 1) incorporating a multisequence MRI technique for improved visualization of the target, OARs, and applicator, and by 2) implementing dose adaptation by use of automated dose tracking tools.
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http://dx.doi.org/10.1120/jacmp.v17i1.5736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5690214PMC
January 2016