Mohamed A. Elshaikh

Impact of marital status on survival among women with invasive cervical cancer: analysis of population-based surveillance, epidemiology, and end results data.

Objective: For some cancers, married individuals present with less advanced stage of disease, receive more aggressive treatment, and live longer after diagnosis compared with unmarried individuals. We examined survival differences by marital status among women with cervical cancer using a population-based sample of patients in the United States while considering patient, tumor, and treatment characteristics. Methods: We identified 7,997 women (1,835 single, 3,849 married, 1,193 separated/divorced, and 1,120 widowed) diagnosed with primary invasive cervical cancer from 1992 to 1996 (with follow-up through December 31, 2004) from the Surveillance, Epidemiology, and End Results program. Associations of marital status, race, age at diagnosis, tumor grade, tumor stage, cancer-directed radiotherapy, and cancer-directed surgery with survival were examined using Cox proportional hazard regression models. Results: Five-year survival was highest for married women and lowest for widowed women (p <.0001). Compared with married women, risks of death for single, separated/divorced, and widowed women were 1.13 (95% confidence interval [CI] = 1.03-1.25), 1.41 (95% CI = 1.28-1.57), and 2.51 (95% CI = 2.29-2.76), respectively. After adjustment, marital status was not independently associated with risk of death (p =.21), although it interacted with tumor stage and cancer-directed radiation therapy. Married women with early stage disease who did not receive radiation therapy had improved survival compared with single, separated/divorced, or widowed women. Conclusions: Marital status interacted with tumor stage and cancer-directed radiation therapy to influence survival among women with cervical cancer. Additional study of the pathways through which partner status influences survival after cancer diagnosis could inform the development of social support interventions.

Contouring variability of human- and deformable-generated contours in radiotherapy for prostate cancer

This study was designed to evaluate contouring variability of human-and deformable-generated contours on planning CT (PCT) and CBCT for ten patients with low-or intermediate-risk prostate cancer. For each patient in this study, five radiation oncologists contoured the prostate, bladder, and rectum, on one PCT dataset and five CBCT datasets. Consensus contours were generated using the STAPLE method in the CERR software package. Observer contours were compared to consensus contour, and contour metrics (Dice coefficient, Hausdorff distance, Contour Distance, Center-of-Mass [COM] Deviation) were calculated. In addition, the first day CBCT was registered to subsequent CBCT fractions (CBCTn: CBCT2-CBCT5) via B-spline Deformable Image Registration (DIR). Contours were transferred from CBCT1 to CBCTn via the deformation field, and contour metrics were calculated through comparison with consensus contours generated from human contour set. The average contour metrics for prostate contours on PCT and CBCT were as follows: Dice coefficient-0.892 (PCT), 0.872 (CBCT-Human), 0.824 (CBCT-Deformed); Hausdorff distance-4.75u2009mm (PCT), 5.22u2009mm (CBCT-Human), 5.94u2009mm (CBCT-Deformed); Contour Distance (overall contour)-1.41u2009mm (PCT), 1.66u2009mm (CBCT-Human), 2.30u2009mm (CBCT-Deformed); COM Deviation-2.01u2009mm (PCT), 2.78u2009mm (CBCT-Human), 3.45u2009mm (CBCT-Deformed). For human contours on PCT and CBCT, the difference in average Dice coefficient between PCT and CBCT (approx. 2%) and Hausdorff distance (approx. 0.5u2009mm) was small compared to the variation between observers for each patient (standard deviation in Dice coefficient of 5% and Hausdorff distance of 2.0u2009mm). However, additional contouring variation was found for the deformable-generated contours (approximately 5.0% decrease in Dice coefficient and 0.7u2009mm increase in Hausdorff distance relative to human-generated contours on CBCT). Though deformable contours provide a reasonable starting point for contouring on CBCT, we conclude that contours generated with B-Spline DIR require physician review and editing if they are to be used in the clinic.

An Adaptive MR-CT Registration Method for MRI-guided Prostate Cancer Radiotherapy

Magnetic Resonance images (MRI) have superior soft tissue contrast compared with CT images. Therefore, MRI might be a better imaging modality to differentiate the prostate from surrounding normal organs. Methods to accurately register MRI to simulation CT images are essential, as we transition the use of MRI into the routine clinic setting. In this study, we present a finite element method (FEM) to improve the performance of a commercially available, B-spline-based registration algorithm in the prostate region. Specifically, prostate contours were delineated independently on ten MRI and CT images using the Eclipse treatment planning system. Each pair of MRI and CT images was registered with the B-spline-based algorithm implemented in the VelocityAI system. A bounding box that contains the prostate volume in the CT image was selected and partitioned into a tetrahedral mesh. An adaptive finite element method was then developed to adjust the displacement vector fields (DVFs) of the B-spline-based registrations within the box. The B-spline and FEM-based registrations were evaluated based on the variations of prostate volume and tumor centroid, the unbalanced energy of the generated DVFs, and the clarity of the reconstructed anatomical structures. The results showed that the volumes of the prostate contours warped with the B-spline-based DVFs changed 10.2% on average, relative to the volumes of the prostate contours on the original MR images. This discrepancy was reduced to 1.5% for the FEM-based DVFs. The average unbalanced energy was 2.65 and 0.38u2009mJu2009cm(-3), and the prostate centroid deviation was 0.37 and 0.28u2009cm, for the B-spline and FEM-based registrations, respectively. Different from the B-spline-warped MR images, the FEM-warped MR images have clear boundaries between prostates and bladders, and their internal prostatic structures are consistent with those of the original MR images. In summary, the developed adaptive FEM method preserves the prostate volume during the transformation between the MR and CT images and improves the accuracy of the B-spline registrations in the prostate region. The approach will be valuable for the development of high-quality MRI-guided radiation therapy.

The impact of tumor grade on survival end points and patterns of recurrence of 949 patients with early-stage endometrioid carcinoma: a single institution study.

Objectives This study aimed to determine the impact of tumor grade on patterns of recurrence and survival end points in patients with endometrioid carcinoma 2009 International Federation of Gynecology and Obstetrics stages I-II. Methods We identified 949 patients who underwent hysterectomy between 1988 and 2011. Patients were divided into 3 groups based on tumor grade. Kaplan-Meier plots were generated for each group for recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS). Results Median follow-up was 52 months. Median age was 60 years. All patients underwent total abdominal hysterectomy and salpingo-oophorectomy. Eighty percent of patients underwent lymph node dissection, 83% had peritoneal cytology. There were 76 (8%) patients who developed tumor recurrence. Tumor recurrence rates were significantly higher in patients with grade 3 tumors compared to grade 1 (P = 0.006). Additionally, patients with grade 3 tumors developed significantly more frequent distant metastases compared to patients with grade 1 (P = 0.002). Five-year RFS for the patients with grade 1, 2, and 3 were 95%, 82%, and 68%, respectively (P = <0.001). Five-year DSS was 99%, 93%, and 79%, respectively (P = <0.001). Five-year OS was 89%, 84%, and 63%, respectively (P = <0.001). Lymphovascular space involvement and grade were significant independent predictors of RFS and DSS. For OS age, lymphovascular space involvement, grade, and body mass index were significant predictors. Conclusions International Federation of Gynecology and Obstetrics grade is a strong predictor of clinical survival end points in women with early-stage endometrioid carcinoma. The pattern of recurrence in patients with grade 3 tumors is mainly distant rather than locoregional. Further studies incorporating systemic therapy in the adjuvant settings in these patients are warranted.

Outcomes of patients with uterine serous carcinoma using the revised FIGO staging system.

Objective Our aim was to evaluate the prognostic significance of the revised 2009 International Federation of Gynecology and Obstetrics (FIGO) staging criteria in patients with uterine serous carcinoma (USC). Materials and Methods We retrieved clinical and histopathologic data on women with USC from 2 large academic centers. Age, race, stage, myometrial invasion, angiolymphatic invasion, and adjuvant therapy were analyzed using Kaplan-Meier and Cox regression models. Results A total of 168 patients were included. Three-year survival rate was 81% for revised stage I, 52% for stage II, 46% for stage III, and 19% for stage IV. Survival was not significantly different when comparing overall 1988 FIGO stage I or II to 2009 FIGO stage I or II. The 3-year survival rate for 1988 stage IA (93%), IB (75%), and IC (60%) significantly differed (P = 0.02). When patients were restaged using the 2009 staging system, the 3-year overall survival of 2009 stage IA dropped to 83.4% and 68.8% for stage IB. New FIGO stage, myometrial invasion, angiolymphatic invasion, and administration of chemotherapy all remained independent predictors of survival on multivariate analysis (P < 0.05). Of note, extrauterine disease was observed in 22% of patients without myometrial invasion. Age and race were not prognostic factors for either classification. Conclusions The streamlined 2009 FIGO criteria do not adequately delineate survival for USC in early-stage disease. The 1988 FIGO classification correctly identified 3 subgroups of stage I USC patients with significantly different survival that is lost with the elimination of the most favorable 1988 stage IA subgroup. Because evaluation for adjuvant therapy and patient planning may change based on survival information, further evaluation of more appropriate USC staging is warranted. Caution should be taken when evaluating therapeutic response and comparing studies using these revised criteria in the future.

The impact of race on survival in uterine serous carcinoma: A hospital-based study

OBJECTIVEnAlthough less common than endometrioid carcinoma, uterine serous carcinoma (USC) accounts for a disproportionate number of endometrial cancer-related deaths. It is relatively more common in black compared to white women. The aim of our study is to analyze the impact of race on survival in USC.nnnMETHODSnWe conducted a retrospective review in women with USC managed at two large urban medical centers. Clinical and histopathologic parameters were retrieved. Recurrence and survival data were obtained from medical records and the Surveillance, Epidemiology, and End Results (SEER) registry. Differences in overall survival between African American and Caucasian women were compared using Kaplan-Meier curves and log rank test for univariate analysis. Cox regression models for multivariate analyses were built to evaluate the relative impact of the various prognostic factors.nnnRESULTSnOne hundred seventy-two women with USC were included in this study, including 65 Caucasian women and 107 African American women. Both groups were similar with respect to age, stage at diagnosis, angiolymphatic invasion (p=0.79), and the depth of myometrial invasion (p=0.36). There was no statistical difference in overall survival between African American and Caucasian patients in univariate analysis (p=0.14). In multivariate analysis, stage at diagnosis, angiolymphatic invasion, and depth of myometrial invasion, but not race, were significantly associated with overall survival.nnnCONCLUSIONnIn this study, African American women with USC had a similar survival to Caucasian women. This suggests that the racial differences seen in USC at a larger population level may be diminished in hospital-based studies, where women are managed in a uniform way.

Predictive Capacity of 3 Comorbidity Indices in Estimating Survival Endpoints in Women With Early-Stage Endometrial Carcinoma.

Objective The negative impact of comorbidity on survival in women with endometrial carcinoma (EC) is well-known. Few validated comorbidity indices are available for clinical use, such as the Charlson Comorbidity Index (CCI), the Age-Adjusted CCI (AACCI), and the Adult Comorbidity Evaluation-27 (ACE-27). The aim of the study is to determine which index best correlates with survival endpoints in women with EC. Materials and Methods We identified 1132 women with early-stage EC treated at an academic center. Three scores were calculated for each patient using CCI, AACCI, and ACE-27 at the time of hysterectomy. Univariate and multivariable modeling was used to determine predictors of survival. Results For each of the studied comorbidity indices, the highest scores were significantly correlated with poorer overall survival. The hazard ratio of death from any cause was 3.92 for AACCI, 2.25 for CCI, and 1.57 for ACE-27. All 3 indices were independent predictors of overall survival with a P value of less than 0.001 on multivariate analysis. In addition, lymphovascular space invasion, lower uterine segment involvement, and tumor grade were predictors of overall survival. Lymphovascular space invasion, grade (P < 0.001), and high AACCI score were the only significant predictors of recurrence-free survival (RFS). Lymphovascular space invasion and tumor grade were the only 2 predictors of disease-specific survival. Conclusions Although all 3 studied comorbidity indices were significant predictors of overall survival in women with early-stage EC, AACCI showed a stronger association. It should be considered for evaluating comorbidity in women with early-stage EC.

Characterization of a commercial hybrid iterative and model-based reconstruction algorithm in radiation oncology.

PURPOSEnIterative reconstruction (IR) reduces noise, thereby allowing dose reduction in computed tomography (CT) while maintaining comparable image quality to filtered back-projection (FBP). This study sought to characterize image quality metrics, delineation, dosimetric assessment, and other aspects necessary to integrate IR into treatment planning.nnnMETHODSnCT images (Brilliance Big Bore v3.6, Philips Healthcare) were acquired of several phantoms using 120 kVp and 25-800 mAs. IR was applied at levels corresponding to noise reduction of 0.89-0.55 with respect to FBP. Noise power spectrum (NPS) analysis was used to characterize noise magnitude and texture. CT to electron density (CT-ED) curves were generated over all IR levels. Uniformity as well as spatial and low contrast resolution were quantified using a CATPHAN phantom. Task specific modulation transfer functions (MTF task) were developed to characterize spatial frequency across objects of varied contrast. A prospective dose reduction study was conducted for 14 patients undergoing interfraction CT scans for high-dose rate brachytherapy. Three physicians performed image quality assessment using a six-point grading scale between the normal-dose FBP (reference), low-dose FBP, and low-dose IR scans for the following metrics: image noise, detectability of the vaginal cuff/bladder interface, spatial resolution, texture, segmentation confidence, and overall image quality. Contouring differences between FBP and IR were quantified for the bladder and rectum via overlap indices (OI) and Dice similarity coefficients (DSC). Line profile and region of interest analyses quantified noise and boundary changes. For two subjects, the impact of IR on external beam dose calculation was assessed via gamma analysis and changes in digitally reconstructed radiographs (DRRs) were quantified.nnnRESULTSnNPS showed large reduction in noise magnitude (50%), and a slight spatial frequency shift (∼ 0.1 mm(-1)) with application of IR at L6. No appreciable changes were observed for CT-ED curves between FBP and IR levels [maximum difference ∼ 13 HU for bone (∼ 1% difference)]. For uniformity, differences were ∼ 1 HU between FBP and IR. Spatial resolution was well conserved; the largest MTFtask decrease between FBP and IR levels was 0.08 A.U. No notable changes in low-contrast detectability were observed and CNR increased substantially with IR. For the patient study, qualitative image grading showed low-dose IR was equivalent to or slightly worse than normal dose FBP, and is superior to low-dose FBP (p < 0.001 for noise), although these did not translate to differences in CT number, contouring ability, or dose calculation. The largest CT number discrepancy from FBP occurred at a bone/tissue interface using the most aggressive IR level [-1.2 ± 4.9 HU (range: -17.6-12.5 HU)]. No clinically significant contour differences were found between IR and FBP, with OIs and DSCs ranging from 0.85 to 0.95. Negligible changes in dose calculation were observed. DRRs preserved anatomical detail with <2% difference in intensity from FBP combined with aggressive IRL6.nnnCONCLUSIONSnThese results support integrating IR into treatment planning. While slight degradation in edges and shift in texture were observed in phantom, patient results show qualitative image grading, contouring ability, and dosimetric parameters were not adversely affected.

Vaginal cuff dehiscence after vaginal cuff brachytherapy for uterine cancer. A case report

Vaginal cuff dehiscence is a rare, but potentially serious complication after total hysterectomy. We report a case of vaginal cuff dehiscence after vaginal cuff brachytherapy. A 62 year old female underwent a robotic-assisted laparoscopic hysterectomy with bilateral salpingo-oophorectomy, and was found to have International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB endometrioid adenocarcinoma of the uterus. The patient was referred for adjuvant vaginal cuff brachytherapy. During the radiation treatment simulation, a computerized tomography (CT) of the pelvis showed abnormal position of the vaginal cylinder. She was found to have vaginal cuff dehiscence that required immediate surgical repair. Vaginal cuff dehiscence triggered by vaginal cuff brachytherapy is very rare with only one case report in the literature.

Vaginal cuff dehiscence after vaginal cuff brachytherapy for uterine cancer. A

Vaginal cuff dehiscence is a rare, but potentially serious complication after total hysterectomy. We report a case of vaginal cuff dehiscence after vaginal cuff brachytherapy. A 62 year old female underwent a robotic-assisted laparoscopic hysterectomy with bilateral salpingo-oophorectomy, and was found to have International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB endometrioid adenocarcinoma of the uterus. The patient was referred for adjuvant vaginal cuff brachytherapy. During the radiation treatment simulation, a computerized tomography (CT) of the pelvis showed abnormal position of the vaginal cylinder. She was found to have vaginal cuff dehiscence that required immediate surgical repair. Vaginal cuff dehiscence triggered by vaginal cuff brachytherapy is very rare with only one case report in the literature.