Predicting outcomes for locally advanced rectal cancer treated with neoadjuvant chemoradiation with CT-based radiomics.

A feasibility study was performed to determine if CT-based radiomics could play an augmentative role in predicting neoadjuvant rectal score (NAR), locoregional failure free survival (LRFFS), distant metastasis free survival (DMFS), disease free survival (DFS) and overall survival (OS) in locally advanced rectal cancer (LARC). The NAR score, which takes into account the pathological tumour and nodal stage as well as clinical tumour stage, is a validated surrogate endpoint used for early determination of treatment response whereby a low NAR score (< 8) has been correlated with better outcomes and high NAR score (> 16) has been correlated with poorer outcomes. CT images of 191 patients with LARC were used in this study. Primary tumour (GTV) and mesorectum (CTV) were contoured separately and radiomics features were extracted from both segments. Two NAR models (NAR > 16 and NAR < 8) models were constructed using Least Absolute Shrinkage and Selection Operator (LASSO) and the survival models were constructed using regularized Cox regressions. Area under curve (AUC) and time-dependent AUC were used to quantify the performance of the LASSO and Cox regression respectively, using ten folds cross validations. The NAR > 16 and NAR < 8 models have an average AUCs of 0.68 ± 0.13 and 0.59 ± 0.14 respectively. There are statistically significant differences between the clinical and combined model for LRFFS (from 0.68 ± 0.04 to 0.72 ± 0.04), DMFS (from 0.68 ± 0.05 to 0.70 ± 0.05) and OS (from 0.64 ± 0.06 to 0.66 ± 0.06). CTV radiomics features were also found to be more important than GTV features in the NAR prediction model. The most important clinical features are age and CEA for NAR > 16 and NAR < 8 models respectively, while the most significant clinical features are age, surgical margin and NAR score across all the four survival models.

Chemoradiation-induced changes in systemic inflammatory markers and their prognostic significance in oesophageal squamous cell carcinoma.

OBJECTIVE: Chemoradiation (CRT) may induce a change in systemic inflammatory state which could affect clinical outcomes in oesophageal cancer. We aimed to evaluate the changes and prognostic significance of systemic inflammatory markers following definitive CRT in oesophageal squamous cell carcinoma. METHODS: A total of 53 patients treated with concurrent CRT were included in this retrospective analysis. We compared neutrophils, lymphocytes, platelets, neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) before and after CRT using Wilcoxon signed-rank test. Overall survival (OS) and progression-free survival (PFS) were calculated. Univariable and multivariable survival analysis were performed using Cox regression analysis. Clinical univariable survival prognostic factors with p < 0.1 were included in a multivariable cox regression analysis for backward stepwise model selection. RESULTS: Both NLR (median ∆+2.8 [IQR -0.11, 8.62], p < 001) and PLR (median ∆+227 [81.3-523.5], p < 0.001) increased significantly after CRT. Higher levels of pre-CRT, post-CRT and change (∆) in NLR and PLR were associated with inferior OS and PFS. Post-CRT NLR (HR 1.04, 95% CI 1.02-1.07, p < 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01-1.05, p = 0.005), cT-stage (HR 3.83, 95% CI 1.39-10.60, p = 0.01) and RT dose (HR 0.41, 95% CI 0.21-0.81, p = 0.01) were independent prognostic factors for OS in multivariable analysis. Change in NLR (HR 1.04, 95% CI 1.01-1.06, p = 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01-1.05, p = 0.002), cT-stage (HR 3.98, 95% CI 1.55-10.25, p = 0.004) and RT dose (HR 0.41, 95% CI 0.21-0.80, p = 0.009) were independent prognostic factors for PFS. CONCLUSION: Both NLR and PLR increased following definitive CRT. Post-CRT NLR and ∆NLR were associated with adverse survival in oesophageal SCC. ADVANCES IN KNOWLEDGE: We showed that CRT increased PLR and NLR, possibly reflecting a systemic inflammatory state which were associated with poor clinical outcomes in oesophageal SCC.

Stage 1C grade 3 endometrial cancer: the KK Hospital gynaecological oncology group experience.

OBJECTIVE: It is our standard of care to include pelvic lymph node dissection (PLND) in the staging of endometrial cancer, followed by adjuvant vaginal vault brachytherapy. We report our experience and outcome of patients with stage 1C grade 3 endometrial cancer from KK Hospital Singapore. METHODS: Records of patients with a diagnosis of stage 1C grade 3 endometrial cancer (based on the 1988 FIGO [International Federation of Gynecology and Obstetrics] staging system) from 1995 to 2008 were retrospectively reviewed. Details of surgery, chemotherapy, and radiotherapy were recorded, as were prognostic factors such as histological subtype and number of lymph nodes removed. Dates and sites of relapses were noted. RESULTS: A total of 31 cases were reviewed; 29 had sufficient records to be analyzed, of which one was excluded as she had a second primary cancer (breast). Median follow-up was 50.1 months (15.5-154 months). All cases underwent total hysterectomy and bilateral salpingo-oophorectomy; the majority (22 [76%]) had PLND as well. Those who did not undergo PLND received external beam radiotherapy instead. All but 1 case received postoperative vaginal vault brachytherapy. Eight of 10 patients with nonendometrioid adenocarcinoma (eg, clear cell) histology also received adjuvant chemotherapy. There were 5 systemic relapses (17.9%) and 1 pelvic recurrence (3.6%). The 5-year disease-free survival is 78.6%. No serious (grade 3 or 4) adverse effects were recorded. CONCLUSION: Pelvic lymph node dissection and vaginal vault brachytherapy seem to be effective in preventing locoregional recurrences, with few associated adverse effects. However, the rate of systemic relapse is relatively high. Adjuvant chemotherapy should also be considered for cases with poor prognostic factors.

Are heart doses associated with survival in patients with non-small cell lung cancer who received post-operative thoracic radiotherapy?: A national population-based study.

The aim of this retrospective national cohort study is to assess the association between various radiation heart dosimetric parameters (RHDPs), acute myocardial infarct (AMI) and overall survival (OS) outcomes in non-small cell lung cancer (NSCLC) patients treated with post-operative thoracic radiotherapy (PORT) using contemporary radiation techniques.We identified patients with stage I to III NSCLC treated with PORT at the 2 national cancer institutions from 2007 to 2014. We linked their electronic medical records to the national AMI and death registries. Univariable Cox regression was performed to assess the association between various RHDPs, AMI, and OS.We included 43 eligible patients with median follow-up of 36.6 months. Median age was 64 years. Majority of the patients had pathological stage III disease (72%). Median prescription dose was 60Gy. Median mean heart dose (MHD) was 9.4Gy. There were no AMI events. The 5-year OS was 34%. Univariable Cox regression showed that age was significantly associated with OS (hazard ratio, 1.06; 95% confidence interval, 1.01 to 1.10; P = .008). Radiation heart doses, including MHD, volume of heart receiving at least 5, 25, 30, 40, 50Gy and dose to 30% of heart volume, were not significantly associated with OS.There is insufficient evidence to conclude that RHDPs are associated with OS for patients with NSCLC treated with PORT in this study. Studies with larger sample size and longer term follow-up are needed to assess AMI outcome.

Late toxicities after conventional radiation therapy alone for nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: We sought to evaluate the nature and frequency of late toxicities in a cohort of nasopharyngeal cancer (NPC) patients treated with conventional radiotherapy alone. METHODS AND MATERIALS: Seven-hundred and ninety-six consecutive NPC patients treated using conventional radiotherapy at a single center from 1992 to 1995 were retrospectively analyzed. Patients with histology proven, completely staged, Stage I-IVB World Health Organization Type I-III NPC and completed radical radiotherapy were included. Patients with incomplete staging investigations, distant metastases at diagnosis, previous treatment, and incomplete radiotherapy were excluded. Radiotherapy-related complications were categorized using the RTOG Late Radiation Morbidity Scoring Criteria. RESULTS: Median follow-up was 7.2 years. The 5-year overall survival and disease free survival were 69% and 56%, respectively, and the corresponding 10-year rates were 52% and 44%. Among 771 patients with at least 3 months of follow-up post treatment, 565 (73%) developed RT-related complications. Diagnosed neurological complications were cranial nerve palsies (n=70; 9%), temporal lobe necrosis (n=37; 5%), Lhermitte's syndrome (n=7; 1%), and brachial plexopathy (n=2; 0.3%). Non-neurological complications included xerostomia (n=353; 46%), neck fibrosis (n=169; 22%), hypo-pituitarism (n=48; 6%), hearing loss (n=120; 16%), dysphagia (n=116; 15%), otorrhea (n=101; 13%), tinnitus (n=94; 12%), permanent tube feeding (n=61; 8%), trismus (n=45; 6%), second malignancies within treatment field (n=17; 2%), and osteo-radionecrosis (n=13; 2%). CONCLUSIONS: While radiotherapy is curative in NPC, many patients suffer significant late treatment morbidities with conventional radiotherapy techniques.