Showing papers by "William Small published in 2017"

Cervical cancer: A global health crisis

Abstract: Cervical cancer is the fourth most common malignancy diagnosed in women worldwide. Nearly all cases of cervical cancer result from infection with the human papillomavirus, and the prevention of cervical cancer includes screening and vaccination. Primary treatment options for patients with cervical cancer may include surgery or a concurrent chemoradiotherapy regimen consisting of cisplatin-based chemotherapy with external beam radiotherapy and brachytherapy. Cervical cancer causes more than one quarter of a million deaths per year as a result of grossly deficient treatments in many developing countries. This warrants a concerted global effort to counter the shocking loss of life and suffering that largely goes unreported. This article provides a review of the biology, prevention, and treatment of cervical cancer, and discusses the global cervical cancer crisis and efforts to improve the prevention and treatment of the disease in underdeveloped countries. Cancer 2017;123:2404-12. © 2017 American Cancer Society.

Cervical Cancer: A Global Health Crisis

Abstract: Cervical cancer is the fourth most common malignancy diagnosed in women worldwide. Nearly all cases of cervical cancer result from infection with the human papillomavirus, and the prevention of cervical cancer includes screening and vaccination. Primary treatment options for patients with cervical cancer may include surgery or a concurrent chemoradiotherapy regimen consisting of cisplatin-based chemotherapy with external beam radiotherapy and brachytherapy. Cervical cancer causes more than one quarter of a million deaths per year as a result of grossly deficient treatments in many developing countries. This warrants a concerted global effort to counter the shocking loss of life and suffering that largely goes unreported. This article provides a review of the biology, prevention, and treatment of cervical cancer, and discusses the global cervical cancer crisis and efforts to improve the prevention and treatment of the disease in underdeveloped countries. Cancer 2017;123:2404-12. © 2017 American Cancer Society.

Intraoperative Radiotherapy for Breast Cancer.

Abstract: Intraoperative radiotherapy (IORT) for early stage breast cancer is a technique for partial breast irradiation. There are several technologies in clinical use to perform breast IORT. Regardless of technique, IORT generally refers to the delivery of a single dose of radiation to the periphery of the tumor bed in the immediate intraoperative time frame, although some protocols have performed IORT as a second procedure. There are two large prospective randomized trials establishing the safety and efficacy of breast IORT in early stage breast cancer patients with sufficient follow-up time on thousands of women. The advantages of IORT for partial breast irradiation include: direct visualization of the target tissue ensuring treatment of the high-risk tissue and eliminating the risk of marginal miss; the use of a single dose coordinated with the necessary surgical excision thereby reducing omission of radiation and the selection of mastectomy for women without access to a radiotherapy facility or unable to undergo several weeks of daily radiation; favorable toxicity profiles; patient convenience and cost savings; radiobiological and tumor microenvironment conditions which lead to enhanced tumor control. The main disadvantage of IORT is the lack of final pathologic information on the tumor size, histology, margins, and nodal status. When unexpected findings on final pathology such as positive margins or positive sentinel nodes predict a higher risk of local or regional recurrence, additional whole breast radiation may be indicated, thereby reducing some of the convenience and low-toxicity advantages of sole IORT. However, IORT as a tumor bed boost has also been studied and appears to be safe with acceptable toxicity. IORT has potential efficacy advantages related to overall survival related to reduced cardiopulmonary radiation doses. It may also be very useful in specific situations, such as prior to oncoplastic reconstruction to improve accuracy of adjuvant radiation delivery, or when used as a boost in higher risk patients to improve tumor control. Ongoing international clinical trials are studying these uses and follow-up data are accumulating on completed studies.

Adaptive Radiotherapy for Head and Neck Cancer.

Abstract: Objective:To investigate the effects of adaptive radiotherapy on dosimetric, clinical, and toxicity outcomes for patients with head and neck cancer undergoing chemoradiotherapy with intensity-modul...

Clinical trials in low and middle-income countries - Successes and challenges.

Abstract: Gynecologic malignancies affect women in low and middle-income countries (LMICs) at equal or higher rates compared to high income countries (HICs), yet practice guidelines based on clinical trials performed in HICs do not routinely account for resource disparities between these regions. There is a need and growing interest for executing clinical trials in LMICs. This has led to the creation of multinational cooperative groups and the initiation of several ongoing clinical trials in Mexico, China, and Korea. In this article we describe the challenges involved in initiating clinical trials in LMICs, review current efforts within surgical, medical, and radiation oncology, and introduce high priority topics for future research.

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

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

Screening for depression in cancer patients receiving radiotherapy: Feasibility and identification of effective tools in the NRG Oncology RTOG 0841 trial.

Abstract: BACKGROUND Brief tools are needed to screen oncology outpatients for depressive symptoms. METHODS Patients starting radiotherapy for the first diagnosis of any tumor completed distress screening tools, including the 9-item Patient Health Questionnaire (PHQ-9), the 2-item Patient Health Questionnaire (PHQ-2), the National Comprehensive Cancer Network Distress Thermometer (NCCN-DT), and the Hopkins Symptom Checklist (HSCL) (25-item version). Patients exceeding validated cutoff scores and a systematic sample of patients whose screening was negative completed the Structured Clinical Interview for DSM-IV (SCID) mood disorder modules via telephone. RESULTS Four hundred sixty-three patients from 35 community-based radiation oncology sites and 2 academic radiation oncology sites were recruited. Sixty-six percent of the 455 eligible patients (n = 299) were women, and the eligible patients had breast (45%), gastrointestinal (11%), lung (10%), gynecologic (6%), or other cancers (27%). Seventy-five (16.5%) exceeded screening cutoffs for depressive symptoms. Forty-two of these patients completed the SCID. Another 37 patients whose screening was negative completed the SCID. Among the 79 patients completing the SCID, 8 (10.1%) met the criteria for major depression, 2 (2.5%) met the criteria for dysthymia, and 6 (7.6%) met the criteria for an adjustment disorder. The PHQ-2 demonstrated good psychometric properties for screening for mood disorders with a cutoff score of ≥3 (receiver operating characteristic area under the curve [AUC], 0.83) and was comparable to the PHQ-9 ( > 9; AUC = 0.85). The NCCN-DT did not detect depression (AUC = 0.59). CONCLUSIONS The PHQ-2 demonstrated good psychometric properties for screening for mood disorders, which were equivalent to the PHQ-9 and superior to the NCCN-DT. These findings support using the PHQ-2 to identify patients in need of further assessment for depression, which has a low prevalence but is a clinically significant comorbidity. These findings could inform the implementation of distress screening accreditation standards. Cancer 2017;123:485–493. © 2016 American Cancer Society.

Adjuvant Chemoradiation Therapy for Cervical Cancer and Effect of Timing and Duration on Treatment Outcome

Abstract: Purpose Worse Treatment outcomes are expected with prolongation of overall treatment time (OTT) during definitive chemoradiotherapy of cervical cancer. In the adjuvant setting, data on the relative importance of OTT and the importance of radiotherapy and chemotherapy synchronization are scarce. Using the National Cancer Data Base, we aimed to evaluate the impact of these treatment variables on overall survival in the adjuvant chemoradiotherapy setting. Methods The analysis included non-metastatic cervical cancer patients undergoing hysterectomy followed by adjuvant chemoradiotherapy. The proportional hazard model estimated the effect of prognostic factors (age, comorbidity, race, tumor size, grade and histology, number of high risk pathologic factors) and time-related variables (surgery to radiotherapy start interval (SR), OTT (radiotherapy start to end dates), package time (from diagnosis date to CRT end date) and optimum chemoradiotherapy synchronization (if chemotherapy and radiation start date coincided) on survival. Results Of the 3051 patients, 60% finished RT within 7 weeks and 85% had optimum chemoradiotherapy. Among other factors, univariate analysis identified longer OTT (hazards ratio (HR): 1.33; p Conclusions Our analysis suggests that prolongation of adjuvant chemoradiotherapy duration beyond 7 weeks is associated with poor survival, and surgery to radiotherapy interval less than 8 weeks should be attempted whenever clinically feasible.

Dilator Use After Vaginal Brachytherapy for Endometrial Cancer: A Randomized Feasibility and Adherence Study.

Abstract: Background Vaginal brachytherapy, a common treatment of endometrial cancer, is associated with high rates of vaginal stenosis. Recommendations for vaginal dilator use to minimize stenosis generally include 3 times per week for approximately 10 minutes per use. However, adherence rates range widely and are generally well less than 50%. Objectives The aims of this study were to assess feasibility of recruitment to a study of dilator use and test a theoretically driven enhanced educational program (EEP) to increase adherence. Methods Eligibility included women treated with postoperative vaginal brachytherapy for stage I to IIIc endometrial cancer. Patients were randomized to either nurse-delivered standard institutional instruction or EEP. Results Of eligible patients, 76% consented, 42 were randomized, and 69% completed the 6-month assessment. Mean age was 58.2 years; 48% were sexually active. There was no difference in adherence between arms. Overall, 20% and 8.3% were adherent to the prescribed use of 3 times per week, and 64% and 16% were adherent to use at least once per week at 6 weeks and 6 months, respectively. Adherence was greater among those motivated by vaginal health and having lower body mass index. Nonadherence was significantly higher among those who are college educated, in the EEP group, and with higher weight. Conclusions Feasibility of recruitment into a study of vaginal dilator use was high. Adherence was low, and there was no difference between groups. Adherence to vaginal dilator use requires novel interventions to test. Implications for practice Nursing education that includes how dilators may maintain vaginal health may improve use because it was a motivator for adherence in this study.

How one institution overcame the challenges to start an MRI-based brachytherapy program for cervical cancer

Abstract: PURPOSE Adaptive magnetic resonance imaging (MRI)-based brachytherapy results in improved local control and decreased high-grade toxicities compared to historical controls. Incorporating MRI into the workflow of a department can be a major challenge when initiating an MRI-based brachytherapy program. This project aims to describe the goals, challenges, and solutions when initiating an MRI-based cervical cancer brachytherapy program at our institution. MATERIAL AND METHODS We describe the 6-month multi-disciplinary planning phase to initiate an MRI-based brachytherapy program. We describe the specific challenges that were encountered prior to treating our first patient. RESULTS We describe the solutions that were realized and executed to solve the challenges that we faced to establish our MRI-based brachytherapy program. We emphasize detailed coordination of care, planning, and communication to make the workflow feasible. We detail the imaging and radiation physics solutions to safely deliver MRI-based brachytherapy. The focus of these efforts is always on the delivery of optimal, state of the art patient care and treatment delivery within the context of our available institutional resources. CONCLUSIONS Previous publications have supported a transition to MRI-based brachytherapy, and this can be safely and efficiently accomplished as described in this manuscript.

Commentary on "Accelerated partial breast irradiation consensus statement: Update of an ASTRO Evidence-Based Consensus Statement".

Abstract: 5 Although the new American Society for Radiation Oncology (ASTRO) consensus statement on accelerated partial breast irradiation (APBI) reflects many important changes relative to case selection and inclusion criteria for APBI, we would like to address our concerns specifically regarding the recommendations on the use of low-energy x-ray intraoperative radiation therapy (IORT). The consensus should include a statement that targeted intraoperative radiation therapy (TARGIT) IORT achieves local control similar to external beam radiation therapy (EBRT) with a potential for a survival benefit.1-4 Although the panel correctly recognized that the local recurrence rate in prepathology (TARGIT given simultaneously during lumpectomy) stratum was NOT significantly different from the whole-breast external beam irradiation (WBI) arm (2.1% vs 1.1%, P = .31), the panel gave “greater weight” to the local recurrence rate of the entire IORT cohort (prepathology and postpathology [TARGIT given after lumpectomy as a second procedure by reopening the wound at a median of 37 days after the initial excision] strata combined). Sometimes the devil is in the details. The TARGIT-A trial specified stratification between preand postpathology before randomization to

Adjuvant External Radiation Impacts Outcome of Pelvis-limited Stage III Endometrial Carcinoma: A Multi-institutional Study.

Abstract: BACKGROUND Adjuvant therapy choice for women with FIGO stage III endometrial carcinoma (EC) is controversial. We investigate the comparative benefit of adjuvant chemotherapy (CT) alone, radiation therapy alone (RT) or in combination (chemotherapy and radiation therapy [CRT]) with respect to recurrence-free survival (RFS) and overall survival (OS) in women with pelvis-limited (PL) EC (stage IIIA, IIIB, and IIIC1). MATERIALS AND METHODS A multi-institutional database of 270 surgically staged women with PLEC was analyzed. Univariate log-rank analyses and Cox regression multivariate analyses (MVA) were performed to identify factors associated with RFS and OS. RESULTS Median RFS and OS were 112 and 130 months, respectively, for the full cohort. Adjuvant treatment was CT in 21%, RT in 27%, and CRT in 47%. Age, year of treatment, grade, histology, and adjuvant treatment were significantly associated with RFS and OS on univariate analysis. PLEC patients receiving CT alone fared worse in terms of RFS (P=0.07 relative to RT and <0.01 relative to CRT). On MVA, CRT retained significantly improved RFS relative to CT (hazard ratio for recurrence 0.38, P<0.01). PLEC patients receiving RT or CRT had improved OS compared with CT, P<0.01 and 0.03, respectively. On MVA, both RT only and CRT retained association with improved OS relative to CT alone (hazard ratio for death, 0.43, P=0.02 and 0.40, P<0.01, respectively). CONCLUSIONS For surgically staged PL stage III EC, treatment regimens incorporating RT were associated with improved survival endpoints relative to CT alone. As such, RT should be considered an important component in the adjuvant management of stage III PLEC.

A multi-institutional analysis of intraoperative radiotherapy for early breast cancer: Does age matter?

Abstract: Background Single-session intraoperative radiation therapy (IORT) minimizes treatment demands associated with traditional whole breast radiation therapy (WBRT) but outcomes on local disease control and morbidity among the elderly is limited. Methods A multi-institutional retrospective registry was established from 19 centers utilizing IORT from 2007 to 2013. Patient, tumor, and treatment variables were analyzed for ages Results We evaluated 686 patients ( Conclusions IORT was associated with a low rate of wound complication and local recurrence on short-term follow-up in this cohort.

ACR Appropriateness Criteria® Resectable Pancreatic Cancer.

Abstract: Management of resectable pancreatic adenocarcinoma continues to present a challenge due to a paucity of high-quality randomized studies. Administration of adjuvant chemotherapy is widely accepted due to the high risk of systemic spread associated with pancreatic adenocarcinoma, but the role of radiation therapy is less clear. This paper reviews literature associated with resectable pancreatic cancer to include prognostic factors to aid in the selection of patients appropriate for adjuvant therapies. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Spectral characterization of tissues in high spectral and spatial resolution MR images: Implications for a classification-based synthetic CT algorithm.

Abstract: Purpose To characterize the spectral parameters of tissues with high spectral and spatial resolution magnetic resonance images to be used as a foundation for a classification-based synthetic CT algorithm. Methods A phantom was constructed consisting of a section of fresh beef leg with bone embedded in 1% agarose gel. The high spectral and spatial (HiSS) resolution MR imaging sequence used had 1.0 mm in-plane resolution and 11.1 Hz spectral resolution. This sequence was used to image the phantom and one patient. Post-processing was performed off-line with IDL and included Fourier transformation of the time-domain data, labeling of fat and water peaks, and fitting the magnitude spectra with Lorentzian functions. Images of the peak height and peak integral of both the water and fat resonances were generated and analyzed. Several regions-of-interest (ROIs) were identified in phantom: bone marrow, cortical bone, adipose tissue, muscle, agar gel, and air; in the patient, no agar gel was present but an ROI of saline in the bladder was analyzed. All spectra were normalized by the noise within each voxel; thus, all parameters are reported in terms of signal-to-noise (SNR). The distributions of tissue spectral parameters were analyzed and scatterplots generated. Water peak height in cortical bone was compared to air using a nonparametric t-test. Composition of the various ROIs in terms of water, fat, or fat and water was also reported. Results In phantom, the scatterplot of peak height (water versus fat) showed good separation of bone marrow and adipose tissue. Water versus fat integral scatterplot showed better separation of muscle and cortical bone than the peak height scatterplot. In the patient data, the distributions of water and fat peak heights were similar to that in phantom, with more overlap of bone marrow and cortical bone than observed in phantom. The relationship between bone marrow and cortical bone for peak integral was better separated than those of peak heights in the patient data. For both the phantom and patient, there was a significant amount of overlap in spectral parameters of cortical bone versus air. Conclusion These results show promising results for utilizing HiSS imaging in a classification-based synthetic CT algorithm. Cortical bone and air overlap was expected due to the short T2* of bone; reducing early echo times would improve the SNR in bone and image data from these early echoes could help differentiate these tissue types. Further studies need to be done with the goal of better separation of air and bone, and to extend the concept to volumetric imaging before it can be clinically applied.

The Impact of an International Network (Gynecologic Cancer InterGroup) for Clinical Research on Global Capacity for Gynecologic Cancer Clinical Trials.

Abstract: Objective The objective of this study was to demonstrate that the construction of the Gynecologic Cancer InterGroup (GCIG) has increased collaboration and accrual to high-quality phase 3 trials at a global level. Materials and Methods The GCIG is a collaboration of 29 international cooperative clinical trial groups committed to conduct of high-quality phase 3 trials among women with gynecologic cancer. A complete bibliography of the reported phase 3 trials has been developed and is available on the GCIG Web site http://www.gciggroup.com. A “GCIG trial” is a trial in which any 2 or more GCIG member groups are formally involved. We reviewed the output of the GCIG from 1997 to 2015 with respect to member participation and quality of publication (impact factor and citation index). The publications are considered in 3 cohorts, 1997 to 2002, 2003 to 2008, and 2009 to 2014, for the purposes of comparison and progress. A social network map has been developed for these publications to identify how the GCIG has increased capacity for clinical trials globally. Results Using a global map, the number of member groups in the GCIG has increased in each of the 3 periods. The total annual number of publications and citations within the 1997 to 2015 period has increased significantly. The average number of citations per publication is demonstrated in each of the 3 periods. The steady increase in the number of citations is used as a proxy for the impact of the publications. The impact factor of the journal and the number of citations are reported for the 10 most highly cited publications. Finally, using a social networking methodology, networking has visibly and numerically increased in each of the 3 periods. Conclusions Evidence supports that the construction of the GCIG has increased collaboration and accrual to high-quality phase 3 trials at a global level among women with gynecologic cancer.