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.

A phase III randomized clinical trial comparing sentinel node biopsy with no retroperitoneal node dissection in apparent early-stage endometrial cancer - ENDO-3: ANZGOG trial 1911/2020.

BACKGROUND: Sentinel node biopsy is a surgical technique to explore lymph nodes for surgical staging of endometrial cancer, which has replaced full retroperitoneal lymph node dissection. However, the effectiveness of sentinel node biopsy, its value to patients, and potential harms compared with no-node dissection have never been shown in a randomized trial. PRIMARY OBJECTIVES: Stage 1 will test recovery from surgery. Stage 2 will compare disease-free survival at 4.5 years between patients randomized to sentinel node biopsy versus no retroperitoneal node dissection. STUDY HYPOTHESIS: The primary hypothesis for stage 1 is that treatment with sentinel node biopsy will not cause detriment to patient outcomes (lymphedema, morbidity, loss of quality of life) and will not increase treatment-related morbidity or health services costs compared with patients treated without a retroperitoneal node dissection at 12 months after surgery. The primary hypothesis for stage 2 is that disease-free survival at 4.5 years after surgery in patients without retroperitoneal node dissection is not inferior to those receiving sentinel node biopsy. TRIAL DESIGN: This phase III, open-label, two-arm, multistage, randomized non-inferiority trial (ENDO-3) will determine the value of sentinel node biopsy for surgical management of endometrial cancer. Patients with endometrial cancer are randomized to receive: (1) laparoscopic/robotic hysterectomy, bilateral salpingo-oophorectomy with sentinel node biopsy or (2) laparoscopic/robotic hysterectomy, bilateral salpingo-oophorectomy without retroperitoneal node dissection. In stage 1, 444 patients will be enrolled to demonstrate feasibility and quality of life. If this is demonstrated, we will enroll another 316 patients in stage 2. MAJOR INCLUSION AND EXCLUSION CRITERIA: Inclusion criteria include women aged 18 years or older with histologically confirmed endometrial cancer; clinical stage 1, who meet the criteria for laparoscopic or robotic total hysterectomy and bilateral salpingo-oophorectomy. Patients with uterine mesenchymal tumors are excluded. PRIMARY ENDPOINTS: The endpoint for stage 1 is surgical recovery, with the proportion of patients returning to usual daily activities at 3 months post-surgery as measured with the EQ-5D. Stage 2 is disease-free survival at 4.5 years. SAMPLE SIZE: 760 participants (both stages). ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Stage 1 commenced in January 2021 and is planned to be completed in December 2024 when 444 participants have completed 12 months' follow-up. Stage 2 will enroll a further 316 participants for a total of 760 patients. TRIAL REGISTRATION: NCT04073706.

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.

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.

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.

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.

Screening of hospital workers for pulmonary tuberculosis in a medical center in Taiwan.

At a medical center in Taiwan, all workers were examined by chest radiography, to determine the prevalence of pulmonary tuberculosis. The prevalence of tuberculosis among all hospital workers was 0.12%, that among nurses was 0.35%, and that among externally contracted cleaners was 0.57%. All of the Mycobacterium tuberculosis isolates recovered from 2 nurses and from a patient with pulmonary tuberculosis were the Beijing strain, but the strains had different serotypes.

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.

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.

Staging for cervix cancer: Role of radiology, surgery and clinical assessment.

Staging is necessary in determining the extent of disease, its prognosis and in the formulation of optimal treatment protocols for patients with cancer. Clinical examination of patients and subsequent histopathological assessment when available has traditionally been used to determine the application of different primary and adjuvant treatment modalities. Over the years, surgery, radiotherapy and chemotherapy all have been used either singly or in combinations, and the resulting survival and patterns of failure studies have contributed much in the development of less toxic and more effective protocols. All three modalities of treatments work through separate mechanisms, and they are effective in different stages of cervix cancer. Even within the same stage, the extent of the disease, tumour volume, tissue infiltration and lymph-node metastases requires the use of differing protocols for the disease control. More recently, advances in magnetic resonance imaging (MRI) and positron emission tomography/computerised tomography (PET/CT) have made it possible to examine many of the prognostic factors non-invasively. In addition to clinical assessment, surgical and radiological staging has enabled us to triage patients far more accurately for surgery or for primary radiotherapy, such as unnecessary multimodality treatments are avoided. Only patients with poor prognosis are subjected to a combined modality treatment. Those with poorer prognosis still can be selected for clinical studies exploring new treatment.

Absence of a relationship between tumor ¹8F-fluorodeoxyglucose standardized uptake value and survival in patients treated with definitive radiotherapy for non-small-cell lung cancer.

INTRODUCTION: A recent meta-analysis suggested that patients with non-small-cell lung cancer (NSCLC) whose primary tumors have a higher standardized uptake value (SUV) derived from F-fluorodeoxyglucose positron emission tomography (PET) have a worse prognosis in comparison with those with tumors with lower values. However, previous analyses have had methodological weaknesses. Furthermore, the prognostic significance over the full range of SUV values in patients treated nonsurgically remains unclear. The aim of this retrospective study was to investigate the relationship between survival and maximum SUV (SUV(max)) analyzed as a continuous variable, in patients with NSCLC, staged using PET/computed tomography (CT) and treated with radiotherapy with or without chemotherapy. METHODS: Eligible patients had a histological diagnosis of NSCLC, were treated with radical radiotherapy with or without chemotherapy as their primary treatment, and had pretreatment PET/CT scans. SUV(max), defined as the maximum pixel SUV value retrieved from the primary tumor, was analyzed primarily as a continuous variable for overall survival. RESULTS: Eighty-eight patients met eligibility criteria: stage I, 19; stage II, 10; and stage III, 59. Median SUV(max) was 15.0 (range, 2.5-56). Higher stage was associated with higher SUV(max) values (p = 0.048). In univariate analysis, there was no evidence of a prognostic effect of SUV(max) (hazard ratio per doubling = 0.83; 95% confidence interval, 0.62-1.11; p = 0.22). Analyzing SUV(max) as a dichotomous variable (median cut point = 15.0), the hazard ratio (high: low) for risk of death was 0.71, with p = 0.18 (95% confidence interval, 0.44-1.15). CONCLUSIONS: In this cohort of patients, increasing SUV(max) derived from F-fluorodeoxyglucose-PET/CT was associated with increasing tumor, node, metastasis (TNM) stage. We found no evidence of an association of increasing SUV(max) with a shorter survival. Previous reports of an association between prognosis and SUV(max) may partly be the result of methodological differences between this study and previous reports and an association between stage and SUV(max).