Adjuvant chemotherapy following chemoradiotherapy as primary treatment for locally advanced cervical cancer versus chemoradiotherapy alone (OUTBACK): an international, open-label, randomised, phase 3 trial.

BACKGROUND: Standard treatment for locally advanced cervical cancer is chemoradiotherapy, but many patients relapse and die of metastatic disease. We aimed to determine the effects on survival of adjuvant chemotherapy after chemoradiotherapy. METHODS: The OUTBACK trial was a multicentre, open-label, randomised, phase 3 trial done in 157 hospitals in Australia, China, Canada, New Zealand, Saudi Arabia, Singapore, and the USA. Eligible participants were aged 18 year or older with histologically confirmed squamous cell carcinoma, adenosquamous cell carcinoma, or adenocarcinoma of the cervix (FIGO 2008 stage IB1 disease with nodal involvement, or stage IB2, II, IIIB, or IVA disease), Eastern Cooperative Oncology Group performance status 0-2, and adequate bone marrow and organ function. Participants were randomly assigned centrally (1:1) using a minimisation approach and stratified by pelvic or common iliac nodal involvement, requirement for extended-field radiotherapy, FIGO 2008 stage, age, and site to receive standard cisplatin-based chemoradiotherapy (40 mg/m2 cisplatin intravenously once-a-week for 5 weeks, during radiotherapy with 45·0-50·4 Gy external beam radiotherapy delivered in fractions of 1·8 Gy to the whole pelvis plus brachytherapy; chemoradiotherapy only group) or standard cisplatin-based chemoradiotherapy followed by adjuvant chemotherapy with four cycles of carboplatin (area under the receiver operator curve 5) and paclitaxel (155 mg/m2) given intravenously on day 1 of a 21 day cycle (adjuvant chemotherapy group). The primary endpoint was overall survival at 5 years, analysed in the intention-to-treat population (ie, all eligible patients who were randomly assigned). Safety was assessed in all patients in the chemoradiotherapy only group who started chemoradiotherapy and all patients in the adjuvant chemotherapy group who received at least one dose of adjuvant chemotherapy. The OUTBACK trial is registered with ClinicalTrials.gov, NCT01414608, and the Australia New Zealand Clinical Trial Registry, ACTRN12610000732088. FINDINGS: Between April 15, 2011, and June 26, 2017, 926 patients were enrolled and randomly assigned to the chemoradiotherapy only group (n=461) or the adjuvant chemotherapy group (n=465), of whom 919 were eligible (456 in the chemoradiotherapy only group and 463 in the adjuvant chemotherapy group; median age 46 years [IQR 37 to 55]; 663 [72%] were White, 121 [13%] were Black or African American, 53 [6%] were Asian, 24 [3%] were Aboriginal or Pacific islander, and 57 [6%] were other races) and included in the analysis. As of data cutoff (April 12, 2021), median follow-up was 60 months (IQR 45 to 65). 5-year overall survival was 72% (95% CI 67 to 76) in the adjuvant chemotherapy group (105 deaths) and 71% (66 to 75) in the chemoradiotherapy only group (116 deaths; difference 1% [95% CI -6 to 7]; hazard ratio 0·90 [95% CI 0·70 to 1·17]; p=0·81). In the safety population, the most common clinically significant grade 3-4 adverse events were decreased neutrophils (71 [20%] in the adjuvant chemotherapy group vs 34 [8%] in the chemoradiotherapy only group), and anaemia (66 [18%] vs 34 [8%]). Serious adverse events occurred in 107 (30%) in the adjuvant chemotherapy group versus 98 (22%) in the chemoradiotherapy only group, most commonly due to infectious complications. There were no treatment-related deaths. INTERPRETATION: Adjuvant carboplatin and paclitaxel chemotherapy given after standard cisplatin-based chemoradiotherapy for unselected locally advanced cervical cancer increased short-term toxicity and did not improve overall survival; therefore, it should not be given in this setting. FUNDING: National Health and Medical Research Council and National Cancer Institute.

Prognostic significance of FIGO 2018 staging of loco-regionally advanced cervical cancer (LRACC) with the use of MRI and PET and implications for treatment selection.

INTRODUCTION: The FIGO 2018 staging of cervix cancer recognizes a total of 11 categories of loco-regionally advanced cervix cancer (LRACC). Whilst incorporating imaging is an improvement over clinical staging (FIGO 2009), this had led to more categories of disease which are not prognostically discrete groups. We aimed to analyze survival according to 2018 FIGO stages of cervix cancer and identify isoprognostic groups of patients based on primary tumor volume and nodal status. METHODS: Patients referred for radiotherapy with curative intent between 1996 and 2014 were eligible. Baseline clinico-pathological and follow up information was retrieved from an ethics-approved institutional prospective database. Patients were classified according to FIGO 2018 staging based on histo-pathology, MRI (tumor volume and local compartmental spread assessment) and PET results (nodal spread). Kaplan-Meier method was used to estimate survival at five years. Following survival analysis using recognized prognostic factors, isoprognostic categories were identified and merged to form 5 isoprognostic groups. RESULTS: Seven hundred and forty-four LRACC patients were included. The median (IQR) follow-up was 5.1 (2.6-8.4) yrs. Stage migration occurred in most patients, showing heterogeneous 5 years survival according to 2018 FIGO stages. In contrast progressively worsening prognosis could be demonstrated in the 5 observed isoprognostic clusters (p < 0.002). CONCLUSION/IMPLICATIONS: Prognosis in LRACC depends on the interplay between primary tumor characteristics, type of local spread and nodal disease. A prospective study of survival and patterns of failure according to isoprognostic clusters would be useful to determine the most appropriate treatment modality and estimate survival as well as better patient selection for clinical trials.

Tumor control after palliative hypofractionated, "Quad-shot," external beam radiotherapy followed by brachytherapy: An effective approach in medically compromised and/or elderly patients with cervix cancer.

Context: Cervix cancer is still a leading cause of death in developing countries. Concurrent chemoradiation (CCRT) over 5 weeks followed by brachytherapy is standard of care in locoregionally advanced cervix cancer. Such prolonged treatment may not be tolerated in medically compromised patients. High-dose interrupted hypofractionated Quad-Shot (QS) radiotherapy with brachytherapy treatment was well tolerated. Aims: This study aims to assess the locoregional tumor control in cervix cancer patients who were treated with QS regimen. Settings and Design: Retrospective. Subjects and Methods: Newly diagnosed histologically confirmed cervix cancer patients who were unfit for conventional CCRT and who were treated with QS protocol between 1999 and 2016 were analyzed. Tumor stage, treatment, and follow-up details were retrieved from an ethics-approved prospective departmental database. Statistical Analysis Used: Descriptive statistics and Kaplan-Meier method were used for estimating survival. Results: Thirty-six patients were available for analysis. The median age was 70.5 (32-92) years. Twenty-two of 36 (61.1%) patients had nodal disease while 33% of all patients had distant metastasis. Of 27 patients who died during follow-up, the local and pelvic control was 75% and 60%, respectively. The median overall survival and progression-free survival were 18.6 months. Grade 3-4 toxicity was observed (16%) in the bowel only. Conclusions: Hypofractionated QS radiotherapy with brachytherapy resulted in an overall 82.1% at least stable disease at the primary site. This treatment regimen was well tolerated and may be considered appropriate for patients who may not be suitable for conventional fully fractionated CCRT.

Incidence of intraoperative hypotension in acute traumatic spinal cord injury and associated factors.

OBJECTIVE: The importance of maintaining mean arterial pressure (MAP) > 85 mm Hg for patients with acute spinal cord injury (SCI) is well documented, because systemic hypotension greatly increases the risk of secondary SCI. Current literature focuses on the ICU setting; however, there is a paucity of data describing the changes in MAP in the operating room (OR). In the present study, the authors investigated the incidence of intraoperative hypotension for patients with acute traumatic SCI as well as any associated factors that may have impacted these findings. METHODS: This retrospective study was performed at a level 1 trauma center from 2015 to 2016. All patients with American Spinal Injury Association (ASIA) score A-D acute traumatic SCIs from C1 to L1 were identified. Those included underwent spinal instrumentation and/or laminectomy decompression. Associated factors investigated include the following: age, body mass index, trauma mechanism of injury, Injury Severity Score, level of SCI, ASIA score, hospital day of surgery, total OR time, need for laminectomy decompression, use of spinal fixation, surgical positioning, blood loss, use of blood products, length of hospital stay, length of ICU stay, and discharge disposition. Intraoperative minute-by-minute MAP recordings were used to determine time spent in various MAP ranges. RESULTS: Thirty-two patients underwent a total of 33 operations. Relative to the total OR time, patients spent an average of 51.9% of their cumulative time with an MAP < 85 mm Hg. Furthermore, 100% of the study population recorded at least one MAP measurement < 85 mm Hg. These hypotensive episodes lasted a mean of 103 cumulative minutes per operative case. Analysis of associated factors demonstrated that fall mechanisms of injury led to a statistically significant increase in intraoperative hypotension compared to motor vehicle collisions/motorcycle collisions (p = 0.033). There were no significant differences in MAP recordings when analyzed according to all other associated factors studied. CONCLUSIONS: This is the first study reporting the incidence of intraoperative hypotension for patients with acute traumatic SCIs, and the results demonstrated higher proportions of relative hypotension than previously reported in the ICU setting. Furthermore, the authors identified that every patient experienced at least one MAP below the target value, which was much greater than the initial hypothesis of 50%. Given the findings of this study, adherence to the MAP protocol intraoperatively needs to be improved to minimize the risk of secondary SCI and associated deleterious neurological outcomes.

The role of positron emission tomography in the selection of patients for salvage hysterectomy following chemoradiotherapy for locally advanced cervical cancer.

BACKGROUND: Patients selection for salvage hysterectomy following chemoradiotherapy of cervical cancer is vital to avoid significant morbidity. The purpose of this study was to describe the role of post-treatment F18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography scanning (FDG-PET/CT) in patient selection for salvage hysterectomy. METHODS: This was a retrospective analysis of 49 patients with cervical cancer treated between January 1996 and December 2012 who were candidates for salvage hysterectomy. RESULTS: Three groups were defined based on institutional treatment guidelines, as experience in using post-treatment FDG-PET/CT to guide management evolved. Group 1 consisted of 15 patients who underwent planned hysterectomy based on clinical, cytological, or histological suspicion. Of these, only three (20%) patients had residual disease on histology. Group 2 consisted of 13 patients who had post-treatment FDG-PET/CT 3-6 months after the completion of chemoradiotherapy due either to suspicion of recurrence on examination or patients thought to be at high risk of recurrence at the primary site. Of these, eight patients had hysterectomy and four patients showed positive histology for residual tumor. Group 3 had 21 patients who showed isolated FDG uptake at the primary site on first FDG-PET/CT scanning at 6 months. A subsequent FDG-PET/CT scan after 3 months showed disease progression in seven and complete metabolic response in 14, and surgery was avoided in all patients. CONCLUSION: FDG-PET/CT scanning at 6 months after radiotherapy is a good tool for assessing treatment response in patients with cervical cancer. In patients with persistent uptake on 6 months post-treatment FDG-PET/CT, repeat imaging at a 3-month interval helps in selecting patients for salvage hysterectomy.

Lateral position and utility of navigation for posterior fixation of unstable cervical fracture with ankylosing spondylitis.

BACKGROUND: Ankylosing spondylitis (AS) is a seronegative spondyloarthropathy within the spectrum of rheumatologic diseases. The systemic inflammation that characterizes AS leads to bone resorption and reformation. Pathologic remodeling may include kyphosis, osteoporosis, and multi-segment auto-fusion. Cervical fractures account for 53-78% of spinal trauma seen with AS. Surgical planning is often challenging owing to spinal deformity, medical comorbidities, the cervicothoracic foci of injury, and gross instability of these fracture. CASE DESCRIPTION: A 55-year-old male with AS was presented with a three-column injury at the C6 level. The C6 vertebra was fractured, minimally displaced, and there was a focal kyphotic deformity. Attempted posterior fixation 2 days after presentation was aborted; the patient could not tolerate prone positioning, and there were further technical limitations to a posterior approach. Cervicothoracic fixation from C2 to T2 was then performed using the right lateral decubitus position employing the Mayfield head holder, a beanbag, and spinal neuronavigation. CONCLUSION: In this study, we presented a unique approach to posterior fixation of an unstable cervicothoracic fracture in a patient with AS utilizing the lateral position and neural navigation under intraoperative physiological monitoring.

Surgical treatment of "intermediate risk" lymph node negative cervical cancer patients without adjuvant radiotherapy-A retrospective cohort study and review of the literature.

OBJECTIVES: The role of adjuvant radiotherapy for lymph node-negative stage IB patients with tumor-related negative prognostic factors is not uniformly accepted. It is advocated based on the GOG 92 trial, which was initiated in 1989. The aim of the current study is to report the oncological outcome of "intermediate risk" patients treated by tailored surgery without adjuvant radiotherapy. Data from two institutions that refer these patients for adjuvant radiotherapy served as a control group. METHODS: Included were patients with stage IB cervical cancer treated with radical hysterectomy and pelvic lymphadenectomy, who had negative pelvic lymph nodes but a combination of negative prognostic factors adopted from the GOG 92 trial. Data were obtained from prospectively collected databases of three institutions. Radical surgery was a single-treatment modality in one of them and in the remaining two institutes it was followed by adjuvant chemoradiation. RESULTS: In 127 patients who received only radical surgery, with a median follow-up of 6.1 years, the local recurrence rate was 1.6% (2 cases), and total recurrence was 6.3% (8 cases). Disease-specific survival at 5 years was 95.7% (91.9%; 99.4%) and 91% (83.7%; 98.3%) at 10 years. The only significant factor for disease-specific survival was tumor size ≥4 cm (P = 0.032). The recurrence rate, local control or overall survival did not differ from the control group. Adjuvant radiotherapy was not a significant prognostic factor within the whole cohort. CONCLUSIONS: An excellent oncological outcome, especially local control, can be achieved by both radical surgery or combined treatment in stage IB lymph node-negative cervical cancer patients with negative prognostic factors. The substantially better outcome than in the GOG 92 trial can be attributed to more accurate pre-operative and pathological staging and an improvement in surgical techniques.

Role of imaging in the routine management of endometrial cancer.

Endometrial cancer is the most common gynecologic cancer in women today. It is surgically staged, and while surgery is the primary treatment modality, the identification of disease extent-in particular extrauterine spread-prior to surgery is important to optimize treatment decision making. Ultrasound and MRI are useful for evaluating the extent of local disease, while CT and PET are used for detecting lymph node or distant metastases. Diffusion-weighted MRI has also been used for detecting small metastatic deposits in lymph nodes and omentum. Extrauterine soft tissue involvement can be detected by ultrasound, CT, MRI, and PET. Recently, intraoperative visualization techniques, such as sentinel lymph node mapping, are increasingly used to avoid extensive surgical staging without compromising treatment. Imaging is also used for planning adjuvant treatment and detection of postoperative residual disease in high-risk patients, monitoring and detecting recurrent disease, and in post-treatment surveillance of asymptomatic patients with high risk of relapse.

Cortical Trajectory Pedicle Screws for the Fixation of Traumatic Thoracolumbar Fractures.

Objective Cortical bone trajectory pedicle screws (CBT) have a different trajectory compared to traditional pedicle screws (PS) and they may confer biomechanical advantages in some patient populations. We hypothesize that the placement of CBT in traumatic thoracolumbar fractures could be an alternative technique to the traditional utilization of PS. Methods Single surgeon, retrospective study was performed at a Level 1 Trauma Center from 2013 to 2017. All patients aged between 18 and 90 years with operative AO classification A, B, and C traumatic thoracolumbar fractures were included. Patients with pathological fractures, active spinal infections, or history of vertebral augmentation were excluded. Age, injury severity score (ISS), AO classification, operative time, estimated blood loss (EBL), length of stay (LOS), and presence of proximal junctional kyphosis (PJK) or construct failure were compared between CBT and PS groups. The PS group was further separated into open reduction internal fixation (ORIF) and minimally invasive spine (MIS) groups. All CBT and ORIF cases were completed via open incisions allowing arthrodesis of the involved lamina and facet joints whereas no arthrodesis was completed in the MIS patients. Choice of technique was at the attending surgeon's discretion. Results The study included 71 patients, out of which 12 received CBT and 59 received PS. Of the 59 PS patients, 39 were ORIF and 20 were MIS. The average operative time was 22.9 minutes less in CBT compared to ORIF (p = 0.24). EBL was 337.50 mL for CBT, 184.33 mL for MIS, and 503.33 mL for ORIF (p = 0.01) demonstrating that MIS technique results in a significantly reduced blood loss. However, EBL was comparable for CBT versus MIS (p > 0.05). ISS was not significantly different between the three groups (p = 0.89). LOS was 4.06 days fewer for CBT patients compared to ORIF patients (p = 0.36). There was one case of construct failure as well as one case of incisional site infection in the PS group, but none were found in the CBT group. Instances of PJK complications were determined by the change in the Cobb angle over time and they were not statistically different between the three groups (p = 0.68). Conclusions CBT is noninferior to PS in the fixation of unstable adult traumatic thoracolumbar fractures. With the exception of EBL, CBT was not statistically different compared to MIS and ORIF. This study establishes a precedent to expand the application of this new technique and investigate with larger sample sizes.

Incidence of dysphagia after odontoid screw fixation of type II odontoid fracture in the elderly.

BACKGROUND: Although surgery may reduce mortality rates from type II odontoid fractures in the elderly population, post-operative dysphagia resulting from screw fixation remains a serious complication. METHODS: We retrospectively performed a chart review of patients over 65 years of age who underwent odontoid screw placement for type II odontoid fractures (2009-2014) and sustained post-operative dysphagia. The severity of dysphagia was determined based on the requirements for modified diets, PEG tubes, and prolonged length of stay (LOS), while costs were based upon discharge disposition (e.g. home vs. rehabilitation facilities) and total hospital costs. RESULTS: The incidence of postoperative dysphagia was 80%; 33% required feeding tubes, and 35% warranted PEG placement. The mean LOS for patients with dysphagia was 5 days longer and the total hospital costs averaged $50,000 higher. CONCLUSIONS: Age over 65 is a significant predictor of post-operative dysphagia in patients undergoing type II odontoid screw fixation. Notably, with each additional year above 65, the likelihood of post-operative dysphagia increased by 12%. Furthermore, postoperative dysphagia statistically increased the LOS and total costs.

A Case-Based Review of the Management of Penetrating Brain Trauma.

Principles of penetrating head trauma management were established by Harvey Cushing in relation to the management of penetrating brain injuries of World War One. Cushing radically debrided the scalp and skull and aggressively irrigated wound tracks to remove foreign bodies. He would then obtain water-tight closure. Cushing significantly decreased infection rates which reportedly limited the major cause of mortality due to penetrating head injuries. Many advances have been made by contributions from World War Two, Korean War, Vietnam War, and Iran/Iraq conflicts. Early radical decompression, with conservative debridement and duraplasty applied to blast-induced penetrating injuries during Operation Iraqi Freedom, has resulted in increased survivability and neurological improvement. Each advance in the management of these injuries is based upon more effectively addressing one or more components of Matson's tenets. This case series reviews the successful management of three patients that presented to a level I trauma center with a penetrating head injury from high-velocity projectiles. Management principles of each patient begin with a proper patient assessment, application of Matson's tenets from the time of injury, and airway control. Surgical management is based upon adherence to Grahm's Guidelines which emphasize criteria centered upon post-resuscitative Glasgow Coma Scale score and appropriate imaging. This case series suggests that proper patient evaluation, adherence to Matson's tenets and to Grahm's Guidelines, and appropriate patient selection for operative management leads to improved survival of patients with penetrating head trauma from high-velocity projectiles.

Glut-1 expression in small cervical biopsies is prognostic in cervical cancers treated with chemoradiation.

BACKGROUND/PURPOSE: Chemoradiation (CRT) is standard therapy for locally advanced cervical cancer (LACC). However, there is a lack of biomarkers to identify patients at high relapse-risk. We examine metabolic (glucose transporter-1 [Glut-1]), hypoxic (hypoxia inducible factor [HIF-1α]; carbonic anhydrase [CA-9]) and proliferative (Ki-67) markers for prognostic utility in LACC. MATERIALS/METHODS: 60 LACC patients treated with CRT had pre-treatment biopsies. Immunohistochemistry was performed for Glut-1, HIF-1a and CA-9, to generate a histoscore from intensity and percentage staining; and Ki-67 scored by percentage of positive cells. For each biomarker, treatment response and survival was compared between low and high-staining groups by logrank testing and multivariate analyses. RESULTS: High Glut-1 expression was associated with inferior progression-free survival (PFS), (hazard ratio [HR] 2.8, p = 0.049) and overall survival (OS), (HR 5.0, p = 0.011) on multifactor analysis adjusting for stage, node positivity, tumour volume and uterine corpus invasion. High Glut-1 correlated with increased risk of distant failure (HR 14.6, p = 0.001) but not local failure. Low Glut-1 was associated with higher complete metabolic response rate on post-therapy positron emission tomography scan (odds ratio 3.4, p = 0.048). Ki-67 was significantly associated with PFS only (HR 1.19 per 10 units increase, p = 0.033). Biomarkers for hypoxia were not associated with outcome. CONCLUSIONS: High Glut-1 in LACC is associated with poor outcome post CRT. If prospectively validated, Glut-1 may help select patients for more intensive treatment regimens.

American Brachytherapy Society: Brachytherapy treatment recommendations for locally advanced cervix cancer for low-income and middle-income countries.

PURPOSE: Most cervix cancer cases occur in low-income and middle-income countries (LMIC), and outcomes are suboptimal, even for early stage disease. Brachytherapy plays a central role in the treatment paradigm, improving both local control and overall survival. The American Brachytherapy Society (ABS) aims to provide guidelines for brachytherapy delivery in resource-limited settings. METHODS AND MATERIALS: A panel of clinicians and physicists with expertise in brachytherapy administration in LMIC was convened. A survey was developed to identify practice patterns at the authors' institutions and was also extended to participants of the Cervix Cancer Research Network. The scientific literature was reviewed to identify consensus papers or review articles with a focus on treatment of locally advanced, unresected cervical cancer in LMIC. RESULTS: Of the 40 participants invited to respond to the survey, 32 responded (response rate 80%). Participants were practicing in 14 different countries including both high-income (China, Singapore, Taiwan, United Kingdom, and United States) and low-income or middle-income countries (Bangladesh, Botswana, Brazil, India, Malaysia, Pakistan, Philippines, Thailand, and Vietnam). Recommendations for modifications to existing ABS guidelines were reviewed by the panel members and are highlighted in this article. CONCLUSIONS: Recommendations for treatment of locally advanced, unresectable cervical cancer in LMIC are presented. The guidelines comment on staging, external beam radiotherapy, use of concurrent chemotherapy, overall treatment duration, use of anesthesia, applicator choice and placement verification, brachytherapy treatment planning including dose and prescription point, recommended reporting and documentation, physics support, and follow-up.

Does the mobilization of circulating tumour cells during cancer therapy cause metastasis?

Despite progressive improvements in the management of patients with locoregionally confined, advanced-stage solid tumours, distant metastasis remains a very common - and usually fatal - mode of failure after attempted curative treatment. Surgery and radiotherapy are the primary curative modalities for these patients, often combined with each other and/or with chemotherapy. Distant metastasis occurring after treatment can arise from previously undetected micrometastases or, alternatively, from persistent locoregional disease. Another possibility is that treatment itself might sometimes cause or promote metastasis. Surgical interventions in patients with cancer, including biopsies, are commonly associated with increased concentrations of circulating tumour cells (CTCs). High CTC numbers are associated with an unfavourable prognosis in many cancers. Radiotherapy and systemic antitumour therapies might also mobilize CTCs. We review the preclinical and clinical data concerning cancer treatments, CTC mobilization and other factors that might promote metastasis. Contemporary treatment regimens represent the best available curative options for patients who might otherwise die from locally confined, advanced-stage cancers; however, if such treatments can promote metastasis, this process must be understood and addressed therapeutically to improve patient survival.

Neuraxial Anesthesia Reduces Lymphatic Flow: Proof-of-Concept in First In-Human Study.

Dilation of lymphatic vessels may contribute to iatrogenic dissemination of cancer cells during surgery. We sought to determine whether neuraxial anesthesia reduces regional lymphatic flow. Using nuclear lymphoscintigraphy, 5 participants receiving spinal anesthesia for brachytherapy had lower extremity lymph flow at rest compared with flow under conditions of spinal anesthesia. Six limbs were analyzed. Four limbs were excluded because of failure to demonstrate lymph flow (1 patient, 2 limbs), colloid injection error (1 limb), and undiagnosed deep vein thrombosis (1 limb). All analyzed limbs showed reduced lymph flow washout from the pedal injection site (range 62%-100%) due to neuraxial anesthesia. Lymph flow was abolished in 3 limbs. We report proof-of-concept that neuraxial anesthesia reduces lymphatic flow through a likely mechanism of sympathectomy.

Clinical outcomes from an innovative protocol using serial ultrasound imaging and a single MR image to guide brachytherapy for locally advanced cervix cancer.

PURPOSE: The aim of this study was to report clinical outcomes in a series of patients who underwent serial ultrasound and a single MRI to plan and verify intracavitary brachytherapy. METHODS AND MATERIALS: Data for patients who were referred for curative intent radiotherapy for International Federation of Gynecology and Obstetrics (FIGO) Stage 1-1V cervix cancer between January 2007 and March 2012 were analyzed. All patients received external beam radiotherapy with concurrent chemotherapy and sequential high-dose rate brachytherapy. Brachytherapy was planned and verified using serial ultrasound imaging and a single MRI. RESULTS: Data from 191 patients were available for analyses. The median (range) followup time was 5.08 (0.25-8.25) years. Five-year local control, failure-free survival, cancer-specific survival, and overall survival were 86%, 57.3%, 70% and 63%, respectively. Mean (standard deviation) combined external beam radiotherapy and brachytherapy target doses, equivalent to doses in 2 Gy fractions were 80.4 Gy10 (3.89), median (range) 80 (49-96) Gy10. Grade 3 or greater gastrointestinal, genitourinary, or vaginal late toxicity occurred in 3%, 1.6%, and 2% of patients, respectively. Survival, patterns of failure, and late complication rates were similar to published series of MRI/CT-based brachytherapy practices. CONCLUSIONS: This large study demonstrates that favorable treatment outcomes can be obtained using a pragmatic and innovative combination of ultrasound and MR imaging.

Carcinoma of the cervix in elderly patients treated with radiotherapy: patterns of care and treatment outcomes.

OBJECTIVE: The aim of this analysis was to examine the management of cervix cancer in elderly patients referred for radiotherapy and the results of treatment in terms of overall survival (OS), relapse-free survival (RFS), and treatment-related toxicities. METHODS: Patients were eligible if they were aged ≥75 years, newly diagnosed with cervix cancer and referred for radiotherapy as part of their treatment. Patient details were retrieved from the gynaecology service database where clinical, histopathological treatment and follow-up data were prospectively collected. RESULTS: From 1998 to 2010, 126 patients aged ≥75 years, met selection criteria. Median age was 81.5 years. Eighty-one patients had definitive radiotherapy, 10 received adjuvant radiotherapy and 35 had palliative radiotherapy. Seventy-one percent of patients had the International Federation of Gynecology and Obstetrics stage 1b-2b disease. Median follow-up was 37 months. OS and RFS at 3 years among those treated with curative intent were 66.6% and 75.9% respectively with majority of patients dying without any evidence of cervix cancer. Grade 2 or more late toxicities were: bladder 5%, bowel 11%, and vagina 27%. Eastern Cooperative Oncology Group (ECOG) status was a significant predictor of OS and RFS with each unit increment in ECOG score increased the risk of death by 1.69 times (p<0.001). CONCLUSION: Following appropriate patient selection, elderly patients treated curatively with radiotherapy for cervix cancer have good disease control. Palliative hypofractionated regimens are well tolerated in patients unsuitable for radical treatment.

Advances and Concepts in Cervical Cancer Trials: A Road Map for the Future.

OBJECTIVE: Cervical cancer is responsible for more than a quarter of a million deaths globally each year, mostly in developing countries, making therapeutic advances in all health care settings a top priority. The Gynecologic Cancer InterGroup (GCIG) is a worldwide collaboration of leading national research groups that develops and promotes multinational trials in gynecologic cancer. In recognition of the pressing need for action, the GCIG convened an international meeting with expert representation from the GCIG groups and selected large sites in low- and middle-income countries. METHODS: The focus was to develop a consensus on several concepts for future clinical trials, which would be developed and promoted by the GCIG and launched with major international participation. The first half of the meeting was devoted to a resume of the current state of the knowledge and identifying the gaps in need of new evidence, validating control arms for present and future clinical trials and identifying national and international barriers for studies of cervix cancers. The second half of the meeting was concerned with achieving consensus on a path forward. RESULTS AND CONCLUSIONS: There were 5 principal outcomes as follows: first, a proposal to expand fertility-preserving options with neoadjuvant chemotherapy; second, validation of the assessment of sentinel lymph nodes using minimally invasive surgery with an emphasis on identification and management of low-volume metastasis, such as isolated tumor cells and micrometastasis; third, evaluation of hypofractionation for palliative and curative radiation under the umbrella of the GCIG Cervix Cancer Research Network; fourth, adding to the advances in antiangiogenesis therapy in the setting of metastatic disease; and fifth, developing a maintenance study among women at high risk of relapse. The latter 2 systemic interventions could study PI3K (phosphatidylinositol-3-kinase) inhibitors, immunotherapy, anti-human papillomavirus approaches, or novel antiangiogenic agents/combinations.