Treatment outcomes of early-stage endometrial cancer patients: A propensity score matching of vaginal brachytherapy versus pelvic radiotherapy.

OBJECTIVES: This study aimed to report the treatment outcomes of radiation therapy for early-stage endometrial cancer patients. In addition, this study intended to identify high-risk factors that require pelvic radiotherapy (PRT) in addition to vaginal brachytherapy (VBT) for intermediate-risk endometrial cancer patients. METHODS: Patients with early-stage endometrial cancer receiving postoperative VBT alone or with PRT were included. Propensity score matching was used to balance the two study groups. The primary endpoint was locoregional recurrence (LRR). Age-adjusted Charlson comorbidity index and substantial lymphovascular space invasion were selected for subgroup analyses to identify the benefits of PRT over VBT alone. RESULTS: From 2005 to 2017, a total of 288 patients underwent analysis following propensity score matching. Of these, 144 received VBT and 144 received PRT. There was no significant difference in 5-year LRR between VBT and PRT for both intermediate (0% vs. 0%) and high-intermediate risk patients (3.5% VBT vs. 5.4% PRT; HR 0.54: 0.05-6.00; p = 0.616). The subgroup analyses revealed no significant factors favoring PRT over VBT. Patients with high comorbidities may have higher risks of non-cancer death after receiving PRT. CONCLUSIONS: Postoperative VBT alone is sufficient for early-stage intermediate-risk endometrial cancer patients.

Screening the risk factors for methamphetamine use in pregnant women not receiving prenatal care.

OBJECTIVE: To develop a screening tool for the risk factors potentially indicating methamphetamine use in pregnant women who are not receiving prenatal care. METHOD: This prospective cohort, Institutional Review Board-approved study was performed at a university hospital in Thailand between January 2017 and January 2019. A screening tool was developed using data from 125 pregnant women not receiving prenatal care upon their first admission for childbearing at the hospital delivery room. Potential factors obtained from the patient's history, physical examination, and methamphetamine use in pregnancy or had a urine amphetamine test positive were entered into a logistic regression analysis. The discriminative ability of the screening tool was expressed by the area under the receiver operating characteristic curve (AUROC) sensitivity and specificity, while bootstrapping was used for internal validation. RESULTS: The screening covered four factors: smoking (odds ratio 7.73, score = 2), drinking (3.81, score = 1), living with a spouse or friend who uses methamphetamine (17.28, score = 3), BP ≥ 130/90 mmHg (2.47, score = 1). The AUROC for the model was 0.87, 95% CI, 0.81-0.93 (SE: 0.03). A total points score ≥3 represented the best cut-off value, with a sensitivity of 81% and specificity of 82%. Across the bootstrapping, the C-statistic for the full screening was 0.86, 95% CI, 0.81-0.93 (SE: 0.03). CONCLUSION: A screening tool was developed with an excellent ability to discriminate the risk factors potentially indicating methamphetamine use in pregnant women not receiving prenatal care. Validation in pregnant women receiving prenatal care still needs to be performed.

Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy followed by adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma.

BACKGROUND: Concurrent chemoradiotherapy followed by adjuvant chemotherapy (CCRT-AC) is currently recommended as the standard treatment for locally advanced nasopharyngeal carcinoma (LA-NPC). Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy (NAC-CCRT) is an alternative strategy for decreasing tumor size and controlling micrometastases before main treatment. The aim of this study was to investigate and compare survival outcomes between LA-NPC patients treated with CCRT-AC and those treated with NAC-CCRT. METHODS: This retrospective cohort study included consecutive histologically confirmed LA-NPC patients that were treated with NAC-CCRT or CCRT-AC at Siriraj Hospital during the March 2010 to October 2014 study period. CCRT in both protocols consisted of 3-week cycles of cisplatin 100 mg/m2 with concurrent radiotherapy. Either NAC or AC consisted of 3-week cycles of cisplatin on day 1 and fluorouracil/leucovorin on days 1-4 for a maximum three cycles. The primary endpoint was 5-year overall survival (OS). Flexible parametric survival analysis was used, because the proportional hazards assumption of Cox regression was violated. RESULTS: Of the 266 LA-NPC patients that received treatment during the study period, 79 received NAC-CCRT and 187 received CCRT-AC. Median follow-up was 37 months. Significantly more patients with advanced clinical stage (stage IVA-IVB) received NAC-CCRT (86% in NAC-CCRT vs. 29% in CCRT-AC; p < 0.001). Compared to CCRT-AC in crude analysis, 3-year and 5-year OS of NAC-CCRT were 72% vs. 86% and 62% vs. 75% respectively (p = 0.059). Interestingly, the 3-year and 5-year post-estimation adjusted OS was 84% and 74% for NAC-CCRT and 81% and 70% for CCRT-AC, respectively (HR: 0.83, 95% confidence interval (CI): 0.45-1.56; p = 0.571). Also, adjusted analysis of distant-metastasis survival, NAC-CCRT showed HR was 0.79 (95% CI:0.37-1.72, p = 0.557). Conversely, adjusted analysis of locoregional relapse (LLR)-free survival revealed NAC-CCRT to have a significantly higher risk of LRR (HR: 2.18, 95% CI: 0.98-4.87; p = 0.057). CONCLUSIONS: The results suggested that prognosis in the NAC-CCRT treated patients was not superior to that of the CCRT-AC treated individuals. In patients that receive neoadjuvant chemotherapy, locoregional relapse should be of concern. High-risk distant metastasis patients (N3 stage) that could achieve survival advantage from NAC-CCRT is an interesting and important topic for further study.

Improving breast cancer detection using ultrasonography in asymptomatic women with non-fatty breast density.

BACKGROUND: Mammography (MX) is a reliable modality for detection of breast cancer in asymptomatic women. Use of additional whole breast ultrasonography (US) for breast cancer screening is widely recognized, in particular in women with dense breast parenchyma. PURPOSE: To determine the subgroup of women, according to breast density and age, who receive most benefit from US following MX for detection of breast cancer in an asymptomatic condition. MATERIAL AND METHODS: The study was conducted in asymptomatic women who had non-fatty breast parenchyma using MX and US during January 2006 and December 2007. Mammographic breast density was classified as recommended by ACR BI-RADS lexicon. Non-fatty breast referred to D2, D3, and D4. US was performed by the same radiologists who interpreted MX with a handheld machine during the same visit. Data on demographics, cancer detection rate (CDR), and incremental cancer detection rate (ICDR) were analyzed using 95% confident interval (CI). RESULTS: Of 14,483 breast cancer screenings in women who had non-fatty breast density, 115 cancers were documented. The mean age of cancer patients was 49.6 years. Of 115 cancers, 105 were evidenced on images (31 with MX alone, 19 with US alone, and 55 with both MX and US). Overall CDR was 7.9 per 1000 examination (95% CI, 6.5-9.5). CDR for MX only (MX-CDR) was 6.5 per 1000 examinations (95% CI, 5.2-7.9). Additional US could significantly improve CDR (P < 0.001; 95% CI, 0.9-2.2); US-ICDR was 1.4 per 1000 examinations. According to age group, the group of 40-59 years had statistically significant improvement of ICDR (P < 0.001). The ICDR was highest in D4 breast density (D4) (US-ICDR = 2.5 per 1000 examinations). CONCLUSION: Use of US adjunct to MX for detection of breast cancer in asymptomatic non-fatty, average-risk women for detection of breast cancer is a promising diagnostic procedure. A significant benefit was documented, in particular, in women aged 40-59 years old, and in women with D4 breast density.

Comparison of 18F-FDG Pet/CT and CT: diagnosis performance in lymphoma patient after treatment.

OBJECTIVE: Retrospectively comparing 18F-FDG PET/CT and CT findings at the same anatomic locations in patients with lymphoma by using a combined PET/CT scanner and to analyze the lesions on both metabolic and anatomic bases to evaluate their sensitivity specificity positive predictive value (PPV), negative predictive value (NPV), and accuracy. We analyzed all studies, all patients, common cell type in this study such as diffuse large B cell lymphoma (DLBCL) and Hodgkin's lymphoma and indication of the study such as restaging for recurrence post-therapy and evaluate residual disease within two months after chemotherapy. MATERIAL AND METHOD: Sixty-seven lymphoma patients were studied PET/CT between January 2007 and December 2012 in Siriraj Hospital. We excluded six patients due to no medial report in our hospital. Sixty-one patients (29 male, 32 female, mean age 46.6 +/- 17.7 years, range 8-75) with NHL and with HL) were analyzed for the result of dual-modality PET/CT They underwent 77 18F-FDG PET/CT studies for restaging, for recurrence post-therapy based on 41 studies and evaluation of residual disease within two months after chemotherapy in 36 studies. RESULTS: The statistical parameters of 18F-FDG PET/CT imaging of lymphoma patients after treatment show significantly better specificity than CT and insignificant high accuracy for all studies, all patients, histology of DLBCL, indication of evaluation of active lymphoma within two months after chemotherapy. The 18F-FDG PET/CT parameters of accuracy and PPV are higher than CT without statistical significance. The 18F-FDG PET/CT is not significantly better than CT for histology of Hodgkin's lymphoma and indication of restaging for recurrence post-therapy Nevertheless, the 18F-FDG PET/CT shows slightly improved specificity PPV and accuracy than CT The sensitivity of CT in this study is high and may be from most of our cases selected post-treatment lymphoma that had a residual mass after treatment. Therefore, the sensitivity of PET scan is not significantly higher when compared with CT scan. CONCLUSION: The PET/CT is better than CT for post-treatment lymphoma patient particularly for cell type of DLBCL and indication for evaluation of active lymphoma within two months after chemotherapy.

Development and Internal Validation of a Prediction Model for Nasopharyngeal Carcinoma: Using BMI and Inflammatory Response for Deciding Sequence of Chemotherapy.

PURPOSE: Concurrent chemoradiotherapy followed by adjuvant chemotherapy (CRT-AC) and induction chemotherapy followed by concurrent chemoradiotherapy (IC-CRT) are among the best treatments in nasopharyngeal carcinoma (NPC). This study aimed to develop a model for deciding the sequence of chemotherapy in NPC. METHODS: Data were separated into two cohorts. The CRT-AC cohort had 295 patients, while the IC-CRT cohort had 112. The predictors were standard factors with BMI and neutrophil-lymphocyte ratio (NLR) to predict overall survival (OS). A flexible parametric survival model was used. RESULTS: A total of 132 (44.7%) and 72 patients (64.3%) died in the CRT-AC and IC-CRT cohorts, respectively. The predictors in the final models were age, sex, T, N, NLR, and BMI. The models of OS for CRT-AC and IC-CRT had concordance indices of 0.689 and 0.712, respectively, with good calibration curves. When changing the burden of disease along with NLR and BMI, we found that CRT-AC was not significantly different OS from IC-CRT when low NLR (<3) and high burden of disease (T3N3). By contrast, CRT-AC was remarkably more effective when there were high levels of NLR (≥3) and BMI (≥25) with any burden of disease (anyT anyN). CONCLUSION: With additional BMI and NLR in model, it could be easier to decide between CRT-AC and IC-CRT in countries with limited health care resources.

Comparison of dosimetric parameters for predicting radiation-induced cataract in paediatric patients.

INTRODUCTION: This study compared the predictive ability of radiation-induced cataract between maximum point dose of the lens (Lens Dmax) ≥7 Gy, mean lens dose (Lens Dmean) ≥7 Gy, Lens Dmax ≥10 Gy, and Lens Dmean ≥10 Gy. METHODS: Patients aged 3-18 years received cranial irradiation or radiation therapy at head and neck area between January 2010 and December 2019 at our institute were included. Patients without baseline and/or follow-up eye examination were excluded. Receiver operating characteristic (ROC) curves identified potential predictors and Cox regression analysed correlations between potential factors and cataract occurrence. RESULTS: Sixty-three patients (122 eyes) were analysed. Cataracts were detected in 14 eyes (11.5%). Median follow-up time was 4 years (range 0.5-10 years), with cataract developing in a median of 2.5 years (range 0.3-7 years). Three patients (21.4%) developed grade ≥3 cataract. Lens Dmean ≥10 Gy was associated with cataract formation. CONCLUSION: Lens Dmean ≥10 Gy showed the highest ability for predicting radiation-induced cataract in paediatric patients. Net reclassification improvement (NRI) suggested that changing lens dose constraint from Dmax <7 Gy to Dmean <10 Gy would miss 7% of cataract cases but avoid 28% of unnecessary restrictions. Adopting a mean lens dose <10 Gy was suggested as a constraint for lens dose.

Non-irradiated area of intraoperative radiotherapy with electron technique: outcomes and pattern of failure in early-stage breast cancer from a single-center, registry study.

INTRODUCTION: Intraoperative radiotherapy (IORT) with electrons has revealed to have higher rates of ipsilateral breast tumor recurrence (IBTR) than external beam radiotherapy in updated large-scale, randomized controlled trials in 2021. This study details the oncological outcomes of IORT with electron beams using our strict IORT policies. We have found new and important observations regarding the location of recurrence. METHODS AND MATERIALS: This is a single institution registry of early-stage breast cancer patients who underwent lumpectomy and electron beam IORT with appropriate cone size. All patients met our pre-excision requirements. The primary endpoint was 5-year IBTR rate, with secondary endpoints being 5-year locoregional failure rate, 5-year distant metastasis rate, 5-year overall survival and, importantly, the failure patterns. RESULTS: Between January 2011 and December 2022, 124 patients were recruited. The median follow-up was 6.7 years. The 5-year IBTR rate was 1.87% (95% CI 0.47-7.29%), which is much lower than the ELIOT trial and comparable with other accelerated partial breast irradiation (APBI) techniques. The 5-year locoregional failure rate was 3.68% (95% CI 1.40-9.52%), and the 5-year distant metastasis rate was 0.88% (95% CI 0.13-6.12%), while the 5-year overall survival rate was 97.52% (95% CI 92.44-99.19%). Six patients experienced IBTR. All recurrences were in surgical area, occurring superficial to the tumor bed and within 1 cm of the skin dermis. This failure pattern is very unique and might be explained by our hypothesis of the non-irradiated area beneath the skin. CONCLUSIONS: IORT with electron beams with strict patient selection criteria and strict large cone size is still an acceptable treatment for select patients with early-stage breast cancer. However, our new findings support extreme caution in the non-irradiated area beneath the skin around the tumor cavity. Given the constraints of our sample size, these findings should be interpreted cautiously and warrant further investigation in larger, more comprehensive studies.

Outcomes of Patients With Breast Cancer Treated With or Without Internal Mammary Irradiation: A Single-Center, Retrospective Propensity Score-Matched Study.

Purpose: Internal mammary lymph node radiation therapy (IMN-RT) has unclear benefits. Historical data were based on only conventional (2-dimensional) radiation techniques. In this 3-dimensional radiation therapy era, we compared the distant metastasis-free survival (DMFS) rates of patients receiving IMN-RT with those who did not include coverage of the IMN (non-IMN-RT). This study aimed to determine the relationship between IMN-RT and distant metastasis control in patients with lymph node-positive breast cancer. Methods and Materials: This was a single-center retrospective cohort study. Patients were divided into 2 groups: IMN-RT and non-IMN-RT. The criterion of the IMN-RT group was that 80% of the prescribed dose covered ≥98% of the Clinical Target Volume of IMN. The primary outcome was 4-year DMFS, and the secondary outcomes were 4-year overall survival, 4-year disease-free survival, and cardiac toxicity. Results: From January 2012 to December 2018, 570 patients were evaluated (IMN-RT, 143 patients; non-IMN-RT, 427 patients). Propensity score matching decreased the number of patients in each group to 139. The median follow-up was 4.3 years. The 4-year DMFS rates were as follows: IMN-RT, 79.1% (95% confidence interval [CI], 70.1%-85.6%), and non-IMN-RT, 82.8% (95% CI, 74.2%-88.7%; P = .43). The groups' 4-year overall survival and disease-free survival rates did not differ. The 4-year overall survival rates were 84.3% (95% CI, 76.4%-89.8%) for IMN-RT and 88.1% (95% CI, 81.0%-92.7%; P = .39) for non-IMN-RT. The 4-year disease-free survival rates were 77.1% (95% CI, 68.1%-83.8%) for IMN-RT and 82.1% (95% CI, 73.6%-88.1%; P = .29) for non-IMN-RT. There was no significant difference in cardiac toxicity (IMN-RT, 1.4%; non-IMN-RT, 1.4%; P = 1.0). Conclusions: In the modern radiation technique era with real-world data, we could not find a benefit of internal mammary irradiation.

Single-bundle versus double-bundle anterior cruciate ligament reconstruction: a meta-analysis.

OBJECTIVE: This meta-analysis study compares the treatment outcomes between single bundle (SB) and double bundle (DB) anterior cruciate ligament reconstructions (ACLR) including manual laxity tests, KT-1000 measurements and functional knee scores including International Knee Documentation Committee (IKDC) and Lysholm scores. DATA SOURCES: Medline, Scopus, Web of Science and Cochrane Central Register of Controlled Trials (January 1985 to March 2008). MATERIAL AND METHOD: All randomized controlled trials reporting one or more outcomes related to single bundle versus double bundle ACLR were recruited in the present study. Random effect models were used to pool the data. Heterogeneity in the effect of treatment was tested on the basis of study quality, randomization status and type of ACLR. RESULTS: There were 2,119 studies initially identified, 7 studies met our inclusion criteria. Four hundred and eighty two patients (238 in SB group and 244 in DB group) were included in the present study. The results of KT 1,000 arthrometry in 7 studies favor DB-ACLR with statistical significance (p < 0.05). Pivot shift test were available for 374 patients from 6 studies, 183 and 191 patients in SB group and DB group respectively. The results favor DB-ACLR with statistical significance (p < 0.001). IKDC scores were available for 257 patients from 4 studies. The results trend to favor DB-ACLR but not statistically significant (p = 0.17). Lysholm scores were available for 174 patients from 3 studies. The results trend to favor DB-ACLR without statistical significance (p = 0.10). CONCLUSION: The present study shows that DB-ACLR provides better AP and rotational stability than SB-ACLR. There is no difference in the results of functional scores. DB-ACLR should be considered in patients who particularly require rotational stability of the knee. In the future, the interesting issue is to develop the functional knee score that is more specific to rotational stability evaluation.

Added survival benefit of whole brain radiotherapy in brain metastatic non-small cell lung cancer: Development and external validation of an individual prediction model.

Background: The heterogeneous survival benefit of whole brain radiotherapy (WBRT) in brain metastatic non-small cell lung cancer (NSCLC) was prospectively evidenced in the Quality of Life after Treatment for Brain Metastases (QUARTZ) trial, resulting in inconsistent guideline recommendations and diverse clinical practices for giving WBRT. The objective of this study was to develop and externally validate an individual prediction model to demonstrate the added survival benefit of WBRT to assist decision making when giving WBRT is undetermined. Methods: For model development, we collected 479 brain metastatic NSCLC patients unfit for surgery or stereotactic radiotherapy techniques at Siriraj Hospital. Potential predictors were age, sex, performance status, histology, genetic mutation, neurological symptoms, extracranial disease, previous systemic treatment, measurable lesions, further systemic treatment, and WBRT. Cox proportional hazard regression was used for survival analysis. We used multiple imputations to handle missing data and a backward selection method for predictor selection. Bootstrapping was used for internal validation, while model performance was assessed with discrimination (c-index) and calibration prediction accuracy. The final model was transformed into a nomogram and a web-based calculator. An independent cohort from Sawanpracharak Hospital was used for external validation. Results: In total, 452 patients in the development cohort died. The median survival time was 4.4 (95% CI, 3.8-4.9) months, with 5.1 months for patients who received WBRT and 2.3 months for those treated with optimal supportive care (OSC). The final model contained favorable predictors: female sex, KPS > 70, receiving additional systemic treatment, and WBRT. Having active extracranial disease, experiencing neurological symptoms, and receiving previous systemic treatment were adverse predictors. After optimism correction, the apparent c-index dropped from 0.71 (95% CI, 0.69-0.74) to 0.70 (95% CI, 0.69-0.73). The predicted and observed values agreed well in all risk groups. Our model performed well in the external validation cohort, with a c-index of 0.66 (95% CI, 0.59-0.73) and an acceptable calibration. Conclusions: This model (https://siriraj-brainmetscore.netlify.app/) predicted the added survival benefit of WBRT for individual brain metastatic NSCLC patients, with satisfactory performance in the development and validation cohorts. The results certify its value in aiding treatment decision-making when the administration of WBRT is unclear.

Vaginal 11-point and volumetric dose related to late vaginal complications in patients with cervical cancer treated with external beam radiotherapy and image-guided adaptive brachytherapy.

OBJECTIVE: To investigate the vaginal 11-point and volumetric dose-toxicity relationships in definitive cervical cancer radiotherapy. METHODS: A retrospective cohort study of patients with cervical cancer with a complete response of at least 12 months was performed. Additional per vaginal examinations and patient-scoring questionnaires on the date of patient enrolment were assessed for vaginal strictures. Retrospective dosimetric analysis of vaginal 11-point and volumetric doses was performed with descriptive and probit analyses to investigate dose-toxicity relationships. RESULTS: Ninety-seven patients were included in the study, with a 20-month median follow-up. The incidence rate of grade 3 vaginal strictures was 22.7%. A comparison between patients with grade 1-3 vaginal strictures revealed significant differences in age, stage, initial tumour size, and vaginal involvement. PIBS + 2, PIBS, PIBS-2, D + 5, and D2cc were all significantly different among grade 1-3 vaginal strictures and showed significant probit coefficients. The lateral dose points were significantly higher in grade 2 strictures, but negative probit coefficients failed to establish causal inferences. Post-estimation analyses yielded effective doses (ED) for 15% and 20% probability of grade 3 vaginal strictures (ED15 and ED20) for PIBS + 2 at 57.4 and 111 Gy3, respectively. PIBS-2 yielded an ED20 of 7 Gy3. D + 5 yielded positive ED10, ED15, and ED20 values of 52.2, 66.6, and 78 Gy3, respectively. CONCLUSIONS: This study showed a significant relationship between age, tumour size, and lower-third vaginal involvement with the incidence of vaginal toxicity. The goal of a cumulative radiotherapy dose of ≤ 55 Gy3 to PIBS + 2, ≤5 Gy3 to PIBS-2, and ≤ 65 Gy3 to D + 5 points may reduce the risk of grade 3 vaginal stenosis to less than 15-20%.

High-dose Intensity-modulated proton therapy versus Standard-dose Intensity-modulated RadIation therapy for esophageal squamous cell carcinoma (HI-SIRI): study protocol for a randomized controlled clinical trial.

BACKGROUND: Chemoradiotherapy is the standard of care for esophageal cancer as a neoadjuvant treatment before surgery, or as a definitive treatment for unresectable disease. Intensity-modulated radiotherapy (IMRT) has been considered the standard radiation technique. However, patients suffer from treatment-related toxicities, and most die from disease progression or recurrence. With emerging technological advancement, proton therapy has theoretical advantages over IMRT because it offers apparent dosimetric benefits to allow dose escalation to the target while better sparing surrounding tissues such as the lungs, heart, liver, and spinal cord. The purpose of this study protocol is to investigate the survival benefit of proton therapy using modern intensity-modulated proton therapy (IMPT) compared to standard IMRT for esophageal cancer. METHODS: This is a two-arm open phase II/III multi-institution randomized controlled trial. Eligible patients will have histologically confirmed squamous cell carcinoma of the thoracic esophagus with no evidence of tracheoesophageal/esophagobronchial fistula or distant metastasis. After stratification according to resectability status (resectable vs. borderline resectable/unresectable), a total of 232 patients will be randomized to receive IMPT or IMRT using a 1:1 allocation ratio. In resectable cases, surgical resection following concurrent chemoradiation will be attempted for the patients who are medically fit at the time of surgery. In those with initially borderline resectable/unresectable disease, definitive concurrent chemoradiation will be performed. The phase II study will assess safety (toxicity and postoperative complications) and feasibility (recruitment rate and chemoradiation dose modification) in 40 patients into each arm. The study will then continue into phase III, further recruit 76 patients into each arm, and compare progression-free survival between IMPT vs IMRT groups. The secondary endpoints will be overall survival, local and distant control, toxicities, health-related quality of life, and cost-utility. This protocol describes a detailed radiotherapy and chemotherapy. DISCUSSION: This randomized clinical trial will demonstrate the clinical benefit of IMPT in esophageal cancer treatment in terms of survival and toxicity outcomes which will further establish high-level evidence for radiation modality in squamous cell carcinoma of the thoracic esophagus. TRIAL REGISTRATION: TCTR20200310006 . Registered 10 March 2020.

Development and validation of a prognostic prediction model including the minor lymphatic pathway for distant metastases in cervical cancer patients.

To develop and validate a prognostic model, including the minor lymphatic pathway (internal iliac and presacral nodes). STUDY DESIGN: Retrospective cohort. PARTICIPANTS: Locally advanced cervical cancer underwent concurrent chemoradiotherapy. SAMPLE SIZE: 397 and 384 patients in the development and validation data set. PREDICTORS: Our new nodal staging system with the minor lymphatic pathway. OUTCOME: Distant metastases. STATISTICAL ANALYSIS: Cox regression; net reclassification improvement (NRI) and decision curve analysis (DCA). Our new nodal system was the strongest predictor. The predictors in the final model were new nodal system, tumor stage, adenocarcinoma, initial hemoglobin, tumor size and age. The nodal system and the pretreatment model had concordance indices of 0.661 and 0.708, respectively, with good calibration curves. Compared to the OUTBACK eligibility criteria, the nodal system showed NRI for both cases (22%) and controls (16%). The pretreatment model showed NRI for cases (31%) and controls (18%). DCA in both models showed threshold probability of 15% and 12%, respectively, when compared with 24% in OUTBACK eligibility criteria. Our new nodal staging system and the pretreatment model could differentiate between high-risk and low-risk patients, thus facilitating decisions to provide more aggressive treatment to prevent distant metastases.

Evaluation and external validation of minor lymphatic pelvic pathway for distant metastases in cervical cancer patients treated with concurrent chemoradiotherapy.

To evaluate and validate the minor lymphatic pathway for distant metastases in cervical cancer. This is a retrospective cohort of cervical cancer patients underwent curative concurrent chemoradiotherapy. We used original dataset from 1 university hospital and validation dataset from 3 university hospitals. Lymphadenopathy status in CT imaging was reviewed by radiologist in either the obturator and external iliac nodes (major pathway) or the internal iliac and presacral nodes (minor pathway). We then used Cox regression to adjust for all potential confounders, including paraaortic nodes, T stage, histology, age, total treatment time, total number of nodes, total short axis of nodes. 397 and 384 patients were in the original and validation datasets (median follow-up period, 59.5 month's). The minor pathway was independent prognostic factor in multivariable analysis [HR=2.64; 95%CI=1.07-6.55; P = 0.036] and [HR=14.84; 95%CI=3.15-70.01; P= 0.001] in original and validation datasets, respectively. Whereas, the major pathway was statistically non-significant. Further validation showed that the minor pathway had the highest HR for distant metastases with both the EMBRACE (HR=6.05; 95% CI=1.30-28.08; P = 0.022) and the FIGO 2018 (HR=7.43; 95% CI=2.94-18.78; P<0.001) in the original dataset. A similar result was found with the validation dataset: EMBRACE, HR=30.91; 95% CI=2.78-343.62; P = 0.005; and FIGO 2018, HR=42.41; 95% CI=8.83-203.60; P<0.001.This is the first clinical study to validate that the minor lymphatic pathway was predominantly associated with distant metastases in cervical cancer. This finding should be validated in larger cohort to further integrate in standard staging for prediction of distant metastases.

Cutoff point of neutrophil-to-lymphocyte ratio for predicting survival in nasopharyngeal carcinoma.

ABSTRACT: Neutrophil-to-lymphocyte ratio (NLR) was reported as an independent prognostic factor in many studies, but its cutoff point was not yet concluded. We set forth to prove and validate cutoff point of NLR as a poor prognostic factor for overall survival (OS) in nonmetastatic nasopharyngeal carcinoma (NPC) patients.Retrospective cohort of nonmetastatic NPC adult patients treated with intensity-modulated radiotherapy with curative aim at Siriraj hospital during 2007 to 2014 was enrolled. NLR was defined as absolute neutrophil count divided by absolute lymphocyte count. OS was the primary outcome. We explored our cutoff value by maximum concordance index (C-index) method, and we validated our cutoff and previously reported cutoff values by categorizing patients as NLR ≤ 3 or >3. Internal validation was done by bootstrapping method.Four hundred sixty-three patients were included. The median follow-up time was 70.8 months. By the end of June 2019, 211 patients had died. In univariable analysis of OS by Cox model, an NLR value of 3 showed the highest C-index (0.548) with an HR of 1.43 (95% CI: 1.08-1.89). After adjustment for body mass index, overall staging, age, gender, and histology in multivariable analysis, an NLR >3 was still an independent prognostic factor of poor OS (HR = 1.34, 95% CI = 1.01-1.79). After internal validation, the resampling method shows no overfitting condition and corrected C-index was 0.547 for univariable analysis.A cutoff point of NLR of 3 from routine blood test was found to be an independent poor prognostic factor among patients with nonmetastatic NPC. This prognostic factor could be included in clinical prediction model of NPC and this further prediction model would select high risk patients for intensive treatment.

Added value of metastatic cervical lymph node group V in nodal staging of nasopharyngeal cancer.

BACKGROUND: Prognostic significance of posterior cervical lymph node metastasis in nasopharyngeal cancer is largely unknown. This study aims to determine the added prognostic significance of cervical lymph node group V to the standard American Joint Committee on Cancer (AJCC) staging system (eighth edition AJCC) of nasopharyngeal patients with cancer treated with intensity-modulated radiation therapy (IMRT) in terms of overall survival (OS), distant metastatic-free survival (DMFS), and disease-free survival (DFS). METHODS AND MATERIALS: A retrospective cohort of 199 consecutively diagnosed nasopharyngeal patients with cancer treated with definitive radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) in the era of IMRT in a large university hospital in endemic area of Southeast Asia. Pre-treatment imaging studies were thoroughly re-evaluated and re-staged by a board-certified radiologist using radiographic criteria for cervical lymph node metastasis. T and N classifications were reclassified according to the eighth AJCC staging system. Group V (Va and Vb) cervical node was evaluated for its added prognostic significance. Cox's proportional hazard model was used to retrieve hazard ratio (HR), 95% confidence interval and P value for N classification. Harrell's C-statistic (concordance index) was used for test of discrimination and internal validation was calculated by bootstrap method. RESULTS: This study demonstrated greater separation of OS with HR of 6.75 (95%CI 1.94-23.51, P = .003) by using group Vb only as N3 compared to HR of 4.70 (95%CI 1.37-16.13, P = .014) by using current standard N3 disease (groups IV and Vb). Similarly, N2 with presence of Va shows worsened DFS with HR of 8.70 (95%CI 1.08-69.67, P = .042) compared to N2 without Va with HR of 5.93 (95%CI 0.76-46.00, P = .089). After incorporating cervical group V into nodal staging, the HR and 95%CI among each group was better separated than the eighth AJCC staging system but without significant improvement in C-index. CONCLUSION: Cervical lymph node group V is a potentially added prognostic factor to standard TNM staging.

Chemotherapy in locally advanced nasopharyngeal carcinoma: an individual patient data meta-analysis of eight randomized trials and 1753 patients.

OBJECTIVES: To study the effect of adding chemotherapy to radiotherapy (RT) on overall survival and event-free survival for patients with nasopharyngeal carcinoma. METHODS AND MATERIALS: This meta-analysis used updated individual patient data from randomized trials comparing chemotherapy plus RT with RT alone in locally advanced nasopharyngeal carcinoma. The log-rank test, stratified by trial, was used for comparisons, and the hazard ratios of death and failure were calculated. RESULTS: Eight trials with 1753 patients were included. One trial with a 2 x 2 design was counted twice in the analysis. The analysis included 11 comparisons using the data from 1975 patients. The median follow-up was 6 years. The pooled hazard ratio of death was 0.82 (95% confidence interval, 0.71-0.94; p = 0.006), corresponding to an absolute survival benefit of 6% at 5 years from the addition of chemotherapy (from 56% to 62%). The pooled hazard ratio of tumor failure or death was 0.76 (95% confidence interval, 0.67-0.86; p < 0.0001), corresponding to an absolute event-free survival benefit of 10% at 5 years from the addition of chemotherapy (from 42% to 52%). A significant interaction was observed between the timing of chemotherapy and overall survival (p = 0.005), explaining the heterogeneity observed in the treatment effect (p = 0.03), with the highest benefit resulting from concomitant chemotherapy. CONCLUSION: Chemotherapy led to a small, but significant, benefit for overall survival and event-free survival. This benefit was essentially observed when chemotherapy was administered concomitantly with RT.

Concurrent chemoradiotherapy for T3-4 and N0-1 nasopharyngeal cancer: Asian multicenter trial of the Forum for Nuclear Cooperation in Asia.

The aim of this study was to evaluate the toxicity and efficacy of radiotherapy concurrent with weekly cisplatin for T3-4 and N0-1 nasopharyngeal cancer. Between 2005 and 2010, 70 patients with nasopharyngeal cancer (T3-4 N0-1 M0, World Health Organization Type 2-3) from Vietnam, Indonesia, Malaysia and Thailand were registered. Patients were treated with 2D radiotherapy concurrent with weekly cisplatin (30 mg/m(2)). Neither adjuvant nor induction chemotherapy was given. Ninety-three percent of the patients completed at least four cycles of weekly cisplatin during radiotherapy. The median total doses for the primary tumor and positive lymph nodes were 70 and 66 Gy, respectively. The median overall treatment time of concurrent chemoradiotherapy was 52 days. No treatment-related deaths occurred. Grade 3-4 acute toxicities of mucositis, nausea/vomiting and leukopenia were observed in 34%, 4% and 4% of patients, respectively. With a median follow-up time of 52 months for the 40 surviving patients, the 3-year local control, locoregional tumor control, distant metastasis-free survival and overall survival rates were 80%, 75%, 74% and 80%, respectively. In conclusion, the current results illustrate that our concurrent chemoradiotherapy regimen was feasible, but disease control remained insufficient. Further research is encouraged in order to improve clinical outcomes.

Clinical review 170: A systematic review and metaanalysis of the effectiveness of radioactive iodine remnant ablation for well-differentiated thyroid cancer.

Radioactive iodine remnant ablation destroys residual thyroid tissue after surgical resection of papillary or follicular thyroid cancer. We systematically reviewed 1543 English references to determine whether remnant ablation decreases the risk of thyroid cancer-related death or recurrence after bilateral thyroidectomy for papillary or follicular thyroid cancer. In 13 cohort studies in which the analysis of thyroid cancer-related outcomes was statistically adjusted to a variable degree for prognostic factors or cointerventions, rates of recurrences of thyroid cancer-related outcomes were significantly decreased in the following: one of seven studies examining thyroid cancer-related mortality, three of six studies examining any tumor recurrence, three of three studies examining locoregional recurrence, and two of three studies examining distant metastases. Thyroid hormone suppressive therapy was not adjusted for in the majority of these analyses. In 18 cohort studies not adjusted for prognostic factors or interventions, the benefit of radioactive iodine ablation in decreasing the thyroid cancer-related mortality and any recurrence at 10 yr was inconsistent among centers. However, pooled analyses were suggestive of a statistically significant treatment effect of ablation for the following 10-yr outcomes: locoregional recurrence (relative risk of 0.31, 95% confidence interval, 0.2, 0.49) and distant metastases (absolute decrease in risk 3%, 95% confidence interval, risk decreases 1-4%). In conclusion, radioactive iodine ablation may be beneficial in decreasing recurrence of well-differentiated thyroid cancer; however, results are inconsistent among centers for some outcomes, and the incremental benefit of remnant ablation in low-risk patients treated with bilateral thyroidectomy and thyroid hormone suppressive therapy is unclear.