Fully automated segmentation and radiomics feature extraction of hypopharyngeal cancer on MRI using deep learning.

OBJECTIVES: To use convolutional neural network for fully automated segmentation and radiomics features extraction of hypopharyngeal cancer (HPC) tumor in MRI. METHODS: MR images were collected from 222 HPC patients, among them 178 patients were used for training, and another 44 patients were recruited for testing. U-Net and DeepLab V3 + architectures were used for training the models. The model performance was evaluated using the dice similarity coefficient (DSC), Jaccard index, and average surface distance. The reliability of radiomics parameters of the tumor extracted by the models was assessed using intraclass correlation coefficient (ICC). RESULTS: The predicted tumor volumes by DeepLab V3 + model and U-Net model were highly correlated with those delineated manually (p < 0.001). The DSC of DeepLab V3 + model was significantly higher than that of U-Net model (0.77 vs 0.75, p < 0.05), particularly in those small tumor volumes of < 10 cm3 (0.74 vs 0.70, p < 0.001). For radiomics extraction of the first-order features, both models exhibited high agreement (ICC: 0.71-0.91) with manual delineation. The radiomics extracted by DeepLab V3 + model had significantly higher ICCs than those extracted by U-Net model for 7 of 19 first-order features and for 8 of 17 shape-based features (p < 0.05). CONCLUSION: Both DeepLab V3 + and U-Net models produced reasonable results in automated segmentation and radiomic features extraction of HPC on MR images, whereas DeepLab V3 + had a better performance than U-Net. CLINICAL RELEVANCE STATEMENT: The deep learning model, DeepLab V3 + , exhibited promising performance in automated tumor segmentation and radiomics extraction for hypopharyngeal cancer on MRI. This approach holds great potential for enhancing the radiotherapy workflow and facilitating prediction of treatment outcomes. KEY POINTS: • DeepLab V3 + and U-Net models produced reasonable results in automated segmentation and radiomic features extraction of HPC on MR images. • DeepLab V3 + model was more accurate than U-Net in automated segmentation, especially on small tumors. • DeepLab V3 + exhibited higher agreement for about half of the first-order and shape-based radiomics features than U-Net.

Comprehensive and clinically accurate head and neck cancer organs-at-risk delineation on a multi-institutional study.

Accurate organ-at-risk (OAR) segmentation is critical to reduce radiotherapy complications. Consensus guidelines recommend delineating over 40 OARs in the head-and-neck (H&N). However, prohibitive labor costs cause most institutions to delineate a substantially smaller subset of OARs, neglecting the dose distributions of other OARs. Here, we present an automated and highly effective stratified OAR segmentation (SOARS) system using deep learning that precisely delineates a comprehensive set of 42 H&N OARs. We train SOARS using 176 patients from an internal institution and independently evaluate it on 1327 external patients across six different institutions. It consistently outperforms other state-of-the-art methods by at least 3-5% in Dice score for each institutional evaluation (up to 36% relative distance error reduction). Crucially, multi-user studies demonstrate that 98% of SOARS predictions need only minor or no revisions to achieve clinical acceptance (reducing workloads by 90%). Moreover, segmentation and dosimetric accuracy are within or smaller than the inter-user variation.

Comparative prognostic value of different preoperative complete blood count cell ratios in patients with oral cavity cancer treated with surgery and postoperative radiotherapy.

BACKGROUND: We sought to compare the prognostic significance of different preoperative complete blood count cell ratios in patients with oral cavity squamous cell carcinoma (OSCC) treated with surgery and postoperative radiotherapy (PORT). METHODS: We retrospectively reviewed the clinical records of 890 patients with OSCC who were treated with surgery and PORT. The following preoperative complete blood count cell ratios were collected: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR). Overall survival (OS), local control, regional control, and distant control (DC) served as the main outcomes of interest. RESULTS: The results of multivariate analysis in the entire study cohort revealed that a low NLR was the only independently favorable marker of both OS (adjusted hazard ratio [HR]: 0.794, 95% confidence interval (CI): 0.656-0.961, bootstrap p = 0.028) and DC (adjusted HR: 0.659, 95% CI: 0.478-0.909, bootstrap p = 0.015). Both LMR and PLR were not retained in the model as independent predictors. Subgroup analyses in high-risk patients (i.e., those bearing T4 disease, N3 disease, or poor differentiation) revealed that a high NLR was a significant adverse risk factor for both OS and DC (all p < 0.03)-with a borderline significance being evident for DC in patients with T4 disease (p = 0.058). CONCLUSIONS: A high pretreatment NLR was an independent unfavorable risk factor for both OS and DC in patients with OSCC who underwent surgery and PORT. No other preoperative complete blood count parameters and cell ratios were found to have prognostic significance.

Primary lung cancer with radioiodine avidity: A thyroid cancer cohort study.

BACKGROUND: A proportion of lung cancers show sodium/iodide symporter (NIS) expression. Lung cancers with NIS expression may uptake radioiodine (RAI) and show RAI-avid lesions on RAI scan for differentiated thyroid cancer (DTC) surveillance. AIM: To investigate the possibility of RAI uptake by lung cancer in a cohort with thyroid cancer. METHODS: RAI-avid lung cancers were analyzed using a prospectively maintained database of patients with thyroid cancer who were registered at a medical center between December 1, 1976 and May 28, 2018. NIS expression in lung cancer was assessed using immunohistochemical staining. RESULTS: Of the 5000 patients with thyroid cancer from the studied dataset, 4602 had DTC. During follow-up, 33 patients developed primary lung cancer. Of these patients, nine received an iodine-131 (131I) scan within 1 year before the diagnosis of lung cancer. One of these nine lung cancers was RAI-avid. NIS expression was evaluated, and three of the eight available lung cancers revealed NIS expression. The proportions of lung cancer cells with NIS expression were 60%, 15%, and 10%. The RAI-avid lung cancer had the highest level of expression (60%). The RAI-avid lung cancer had a spiculated border upon single-photon emission computed tomography/computed tomography, which led to an accurate diagnosis. CONCLUSION: A proportion of lung cancer demonstrates NIS expression and is RAI-avid. Clinicians should be aware of this possibility in the interpretation of RAI scintigraphy.

Multi-Institutional Validation of Two-Streamed Deep Learning Method for Automated Delineation of Esophageal Gross Tumor Volume Using Planning CT and FDG-PET/CT.

BACKGROUND: The current clinical workflow for esophageal gross tumor volume (GTV) contouring relies on manual delineation with high labor costs and inter-user variability. PURPOSE: To validate the clinical applicability of a deep learning multimodality esophageal GTV contouring model, developed at one institution whereas tested at multiple institutions. MATERIALS AND METHODS: We collected 606 patients with esophageal cancer retrospectively from four institutions. Among them, 252 patients from institution 1 contained both a treatment planning CT (pCT) and a pair of diagnostic FDG-PET/CT; 354 patients from three other institutions had only pCT scans under different staging protocols or lacking PET scanners. A two-streamed deep learning model for GTV segmentation was developed using pCT and PET/CT scans of a subset (148 patients) from institution 1. This built model had the flexibility of segmenting GTVs via only pCT or pCT+PET/CT combined when available. For independent evaluation, the remaining 104 patients from institution 1 behaved as an unseen internal testing, and 354 patients from the other three institutions were used for external testing. Degrees of manual revision were further evaluated by human experts to assess the contour-editing effort. Furthermore, the deep model's performance was compared against four radiation oncologists in a multi-user study using 20 randomly chosen external patients. Contouring accuracy and time were recorded for the pre- and post-deep learning-assisted delineation process.

DeepTarget: Gross tumor and clinical target volume segmentation in esophageal cancer radiotherapy.

Gross tumor volume (GTV) and clinical target volume (CTV) delineation are two critical steps in the cancer radiotherapy planning. GTV defines the primary treatment area of the gross tumor, while CTV outlines the sub-clinical malignant disease. Automatic GTV and CTV segmentation are both challenging for distinct reasons: GTV segmentation relies on the radiotherapy computed tomography (RTCT) image appearance, which suffers from poor contrast with the surrounding tissues, while CTV delineation relies on a mixture of predefined and judgement-based margins. High intra- and inter-user variability makes this a particularly difficult task. We develop tailored methods solving each task in the esophageal cancer radiotherapy, together leading to a comprehensive solution for the target contouring task. Specifically, we integrate the RTCT and positron emission tomography (PET) modalities together into a two-stream chained deep fusion framework taking advantage of both modalities to facilitate more accurate GTV segmentation. For CTV segmentation, since it is highly context-dependent-it must encompass the GTV and involved lymph nodes while also avoiding excessive exposure to the organs at risk-we formulate it as a deep contextual appearance-based problem using encoded spatial distances of these anatomical structures. This better emulates the margin- and appearance-based CTV delineation performed by oncologists. Adding to our contributions, for the GTV segmentation we propose a simple yet effective progressive semantically-nested network (PSNN) backbone that outperforms more complicated models. Our work is the first to provide a comprehensive solution for the esophageal GTV and CTV segmentation in radiotherapy planning. Extensive 4-fold cross-validation on 148 esophageal cancer patients, the largest analysis to date, was carried out for both tasks. The results demonstrate that our GTV and CTV segmentation approaches significantly improve the performance over previous state-of-the-art works, e.g., by 8.7% increases in Dice score (DSC) and 32.9mm reduction in Hausdorff distance (HD) for GTV segmentation, and by 3.4% increases in DSC and 29.4mm reduction in HD for CTV segmentation.

Prognostic significance of the preoperative systemic immune-inflammation index in patients with oral cavity squamous cell carcinoma treated with curative surgery and adjuvant therapy.

OBJECTIVES: To investigate the prognostic value of the preoperative systemic immune-inflammation index (SII) in patients with oral cavity squamous cell carcinoma (OC-SCC) treated with curative surgery followed by adjuvant radiotherapy (RT) or chemoradiotherapy (CCRT). MATERIALS AND METHODS: We retrospectively reviewed the clinical records of patients with OC-SCC who received surgery and postoperative adjuvant RT/CCRT between January 2005 and December 2012. Blood samples were drawn in the 2 weeks preceding surgery. SII was calculated by multiplying the absolute neutrophil and platelet counts, and then, divided by the absolute lymphocyte count, and its optimal cutoff value was identified using the Youden's index. The study endpoints included overall survival (OS), local control (LC), regional control (RC), and distant control (DC). RESULTS: The study sample consisted of 993 patients (58.8% of them treated with CCRT). The optimal cutoff value for SII was 810.6. A total of 347 (34.9%) study participants had high preoperative SII values. After allowance for potential confounders in multivariable analysis, high SII values were independently associated with less favorable DC (adjusted hazard ratio [HR] = 1.683, p = 0.001) and OS (adjusted HR = 1.466, p < 0.001). No independent association between SII and LC/RC was observed. CONCLUSION: Increased SII values predict poor DC and OS in patients with OC-SCC treated with curative resection and adjuvant RT/CCRT. Owing to the higher risk of systemic failure in this patient group, a thorough follow-up surveillance schedule may be advisable pending independent confirmation of our data.

Prognostic significance of dynamic changes in lymphocyte-to-monocyte ratio in patients with head and neck cancer treated with radiotherapy: results from a large cohort study.

BACKGROUND AND PURPOSE: We sought to investigate whether dynamic changes in lymphocyte-to-monocyte ratio (LMR) occurring during the course of radiotherapy (RT) may have prognostic value in patients with head and neck cancer (HNC). MATERIALS AND METHODS: We retrospectively reviewed the clinical records of patients with HNC who underwent RT at our center between 2005 and 2013. Generalized estimating equations were used to longitudinally assess changes in LMR through the course of RT. Delta-LMR was calculated as the difference between LMR measured during treatment and baseline LMR values. Freedom from metastasis (FFM) and overall survival (OS) served as the main outcome measures. RESULTS: A total of 1431 patients with HNC were enrolled. After a median follow-up of 9 years, 636 (44.4%) patients died and 240 (16.8%) had distant metastases. Compared with patients with low delta-LMR at two weeks, those with high delta-LMR experienced less favorable outcomes (five-year OS: 73% versus 59%, respectively, p < 0.001; five-year FFM: 87% versus 80%, respectively, p = 0.015). Similar findings were observed for delta-LMR measured at four weeks (five-year OS: 72% versus 60%, p < 0.001; five-year FFM: 86% versus 79%, respectively, p = 0.002) and six weeks (five-year OS: 72% versus 57%, p < 0.001; five-year FFM: 87% versus 79%, respectively, p = 0.002). Multivariate analysis identified delta-LMR as an independent prognostic factor for both FFM and OS. CONCLUSION: Delta-LMR is a simple and inexpensive biomarker that may be clinically useful for predicting FFM and OS in patients with HNC treated with RT.

Classifying Neck Lymph Nodes of Head and Neck Squamous Cell Carcinoma in MRI Images with Radiomic Features.

The aim of this study is to develop a computer-aided diagnosis method to help classify medical images of neck lymph nodes in head and neck cancer patients. According to the current practice guidelines, the classification of lymph node status is critical for patient stratification before treatment. Take extra-nodal extension (ENE) of metastatic neck lymph nodes, the status of ENE has been considered a single factor affecting the decision of whether systemic treatment with toxicity should be given to patients with otherwise non-advanced cancer status. Medical imaging prior to surgery serves as tools for clinical staging and determining the extent of neck lymph node dissection during the tumor resection surgery. The information contained in these images may also help determine the status of ENE and thus stratify patients for more precise treatment. In the current practice, there has been not a reliable computer-aided tool for this task. In this study, we used open-source software to investigate radiomic features that help distinguish malignant from benign and ENE from non-ENE lymph nodes. We have identified 89 features that can differentiate malignant from benign and 4 features that can differentiate ENE from non-ENE lymph nodes. Furthermore, we fed the significant features to a multilayer perceptron neural network to predict malignancy and ENE of lymph nodes and achieved 84% and 77% of accuracy in each task, respectively.

Sentinel Lymph Node Biopsy Was Associated With Favorable Survival Outcomes For Patients With Clinically Node-Negative Asian Melanoma.

PURPOSE: Sentinel lymph node biopsy (SLNB) is the standard management for clinically node-negative cutaneous melanoma patients. This study aimed to evaluate the role of SLNB in Taiwanese melanoma patients and in particular, patients with acral lentiginous melanoma (ALM). PATIENTS AND METHODS: We retrospectively analyzed the clinicopathological characteristics and survival outcomes of the patients who underwent primary surgery followed by either SLNB or nodal observation at the Linkou Chang Gung Memorial Hospital from January 2000 to December 2011. RESULTS: Among the total of 209 patients, 127 underwent SLNB and 51 underwent nodal observation only after primary surgery. There were no significant differences in clinicopathological features between the two groups except that patients who underwent SLNB were older and had a higher rate of ALM than those under nodal observation. The median follow-up time was 43.5 months until July 2013. The patients who underwent SLNB had significantly better disease-free survival (DFS) (57.1 vs 18.7 months, p < 0.01) and melanoma-specific survival (MSS) (112.4 vs 45.2 months, p < 0.01) than those under observation. Improvement in DFS (HR: 0.51, p < 0.01) and MSS (HR: 0.60, p = 0.03) was observed even after adjusting for age and disease pathology by multivariate analysis. This benefit of clinical outcomes persisted in patients with ALM, Breslow thickness ≤2 mm, or no ulceration, but not in patients with non-ALM, Breslow thickness >2 mm, or ulceration. CONCLUSION: SLNB was associated with favorable outcomes in patients with clinically node-negative cutaneous melanoma, particularly in Taiwanese patients with ALM, Breslow thickness ≤2 mm, and nonulcerated melanoma.

Merkel cell carcinoma in Taiwan: A series of 24 cases and literature review.

Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine carcinoma of the skin. The available reports of MCC in Asia are limited; in this study, we report the largest series of MCC in Taiwan to date.The series is composed by 24 pathologically proven MCC cases, which were retrospectively reviewed in Chang Gung Memorial Hospital in Taiwan between 2000 and 2018.The tumor occurred predominantly in men (80%) and in the elderly (median 74.8 years). Twenty-one patients had locoregional MCC and 3 had metastatic MCC at the time of diagnosis. Patients with pathologically proven negative nodes by sentinel lymph node biopsy (SLNB) showed better survival time than those without SLNB in 16 clinically node-negative MCC cases undergoing primary surgery. Salvage surgery for loco-regional recurrence lengthened the survival time and possibly cured recurrent MCC. Palliative chemotherapy with cisplatin and etoposide showed a response rate of 25%, progression-free survival of 3.6 months, and overall survival of 14.8 months in 4 metastatic/recurrent MCC. Avelumab treatment was effective in 1 patient, who achieved a durable disease control.This observational cohort of MCC patients in Taiwan suggests aggressive surgical intervention including wide excision and lymph node management, salvage operation is critical for early MCC patients, and palliative chemotherapy and immunotherapy showed their efficacy for advanced MCC patients.

Higher body weight and distant metastasis are associated with higher radiation exposure to the household environment from patients with thyroid cancer after radioactive iodine therapy.

There were insufficient data regarding radiation exposure to the household environment from patients with thyroid cancer who received radioactive iodine (RAI) therapy in Asia; we therefore performed the present study at the Chang Gung Memorial Hospital in Keelung, Taiwan.Patients with papillary or follicular thyroid cancer who received 3.7 GBq (100 mCi) RAI were enrolled in this prospective hospital-based study. The enrolled patients were asked to place a thermoluminescent dosimeter in the living room, bedroom, and bathroom of their houses for 4 weeks to measure radiation exposure to the household environment.A total of 43 patients (18 men and 25 women; mean age 51 ±â€Š13 years) who received 3.7 GBq (100 mCi) RAI completed the study. The mean value of total radiation exposure over 4 weeks from the patients to the bedroom, bathroom, and living room (eliminating the background radiation factor) was 0.446 ±â€Š0.304 (0.088-1.382) mSv. We divided the patients into 2 groups: those with more than and less than the mean value of total radiation exposure to the bedroom, bathroom, and living room. Factors associated with the higher amount of radiation exposure from the patients to the household environment were patient body weight (P = .025, univariate analysis; P = .037, multivariate analysis, odds ratio [95% confidence interval] 1.067 [1.004-1.134]) and distant metastases based on I post-therapy scanning (P = .041, univariate analysis; P = .058, multivariate analysis, odds ratio [95% confidence interval] 6.453 [0.938-44.369]); age, sex, body mass index, renal function, serum stimulated thyroglobulin level, and recombinant human thyroid-stimulating hormone use were not associated with the amount of radiation exposure from the patients to the household environment.Higher body weight and distant metastases may be the best predictors for higher radiation exposure to the household environment from patients with thyroid cancer after RAI therapy.

Dose-escalated radiation therapy is associated with better overall survival in patients with bone metastases from solid tumors: a propensity score-matched study.

We aimed to compare the overall survival (OS) of patients with bone metastases (BM) from solid tumors after standard-dose radiotherapy ([RT]; 30 Gy administered in 10 fractions; EQD2Gy  = 32.5 Gy) and dose-escalated RT (EQD2Gy  > 32.5 Gy). We retrospectively reviewed the clinical charts of 1795 patients (median age, 62.3 years; age range, 18-96 years) with BM from solid tumors who were referred for RT to our institute between 2000 and 2013. These patients were assigned to the standard-dose (n = 1125; 63%) and dose-escalated (n = 670; 37%) RT groups. OS, estimated as the duration between the first RT session and death, served as the main outcome measure. The dose-escalated RT group had a significantly better OS than the standard-dose RT group (P = 0.000). After allowing potential confounders in multivariate analysis, the RT dose retained its independent association with OS (hazard ratio [HR], 0.837; 95% confidence interval [CI], 0.753-0.929, P = 0.001). After propensity score matching of the baseline characteristics of both groups, RT dose retained its independent association with OS (HR, 0.887; 95% CI, 0.737-0.951; P = 0.011) on multivariate analysis. Dose-escalated RT exerted more favorable effects on OS in patients with non-lung cancer, those without multiple metastases, those without symptoms, and those with favorable prognosis. Dose-escalated RT was significantly associated with better OS in patients with BM from solid malignancies, particularly among those with non-lung cancer, those without multiple metastases, those without symptoms, and those with favorable prognosis.

A preliminary investigation into textural features of intratumoral metabolic heterogeneity in (18)F-FDG PET for overall survival prognosis in patients with bulky cervical cancer treated with definitive concurrent chemoradiotherapy.

We examined the role of intratumoral metabolic heterogeneity on (18)F-FDG PET during concurrent chemoradiotherapy (CCRT) in predicting survival outcomes for patients with cervical cancer. This prospective study consisted of 44 patients with bulky (≥ 4 cm) cervical cancer treated with CCRT. All patients underwent serial (18)F-FDG PET studies. Primary cervical tumor standardized uptake values, metabolic tumor volume, and total lesion glycolysis (TLG) were measured in pretreatment and intra-treatment (2 weeks) PET scans. Regional textural features were analyzed using the grey level run length encoding method (GLRLM) and grey-level size zone matrix. Associations between PET parameters and overall survival (OS) were tested by Kaplan-Meier analysis and Cox regression model. In univariate analysis, pretreatment grey-level nonuniformity (GLNU) > 48 by GLRLM textural analysis and intra-treatment decline of run length nonuniformity < 55% and the decline of TLG (∆TLG) < 60% were associated with significantly worse OS. In multivariate analysis, only ∆TLG was significant (P = 0.009). Combining pretreatment with intra-treatment factors, we defined the patients with a initial GLNU > 48 and a ∆TLG ≤ 60% as the high-risk group and the other patients as the low-risk. The 5-year OS rate for the high-risk group was significantly worse than that for the low-risk group (42% vs. 81%, respectively, P = 0.001). The heterogeneity of intratumoral FDG distribution and the early temporal change in TLG may be an important predictor for OS in patients with bulky cervical cancer. This gives the opportunity to adjust individualized regimens early in the treatment course.

Risk factors of distant metastasis in the follicular variant of papillary thyroid carcinoma.

BACKGROUND/PURPOSE: The follicular variant of papillary thyroid carcinoma (FVPTC) is the most common variant of papillary thyroid carcinoma (PTC). A previous population-based study revealed its clinical behavior as a mix of classic papillary thyroid carcinoma (C-PTC) and follicular thyroid carcinoma. Whereas locoregional extension was lower in FVPTC than in C-PTC, the distant metastasis rate was higher in FVPTC than in C-PTC. The aim of this study was to evaluate the risk factors of distant metastasis in FVPTC postoperatively. METHODS: A retrospective review of 359 patients with final pathological diagnosis of FVPTC treated at Chang Gung Memorial Hospital between January 2000 and January 2014 was performed. After excluding patients who had inadequate pathological data for analysis or did not attend regular follow up for >1 year, 346 patients were included in this study. Univariate and multivariate statistical analyses were performed to determine the significance of various factors. RESULTS: Of the 346 patients with FVPTC, 19 (5.5%) had lymph node metastases and 32 (9.2%) had distant metastases. Two positive and one negative risk factors were predictive for distant metastasis using multivariate analysis: angiolymphatic invasion [odds ratio (OR), 3.085; 95% confidence interval (CI), 1.008-9.442], extrathyroidal extension (OR, 3.929; 95% CI, 1.330-11.602), and encapsulation (OR, 0.361; 95% CI, 0.154-0.850). CONCLUSION: The presence of angiolymphatic invasion, extrathyroidal extension, or nonencapsulation was associated with distant metastasis in FVPTC in this study. In FVPTC patients, postoperative investigation for distant metastasis may be warranted by the presence of these two positive risk factors or the absence of the one negative risk factor.

Total lesion glycolysis determined per RECIST 1.1 criteria predicts survival in EGFR mutation-negative patients with advanced lung adenocarcinoma.

OBJECTIVE: The aim of this retrospective study was to investigate the clinical impact of F-FDG PET in patients with advanced lung adenocarcinoma stratified according to the epidermal growth factor receptor (EGFR) mutation status. PATIENTS AND METHODS: A total of 56 patients with advanced lung adenocarcinoma were included in the study. Thirty-one patients (55%) were EGFR mutation-positive, whereas the remaining 25 (45%) participants tested negative for EGFR mutations. All of the patients underwent F-FDG PET/CT for pretreatment planning. The main outcome measure was overall survival (OS) at 24 months. The following F-FDG PET/CT-derived variables were tested for their associations with OS: main tumor SUVmax, main tumor total lesion glycolysis, and target lesions TLG determined per RECIST (Response Evaluation Criteria In Solid Tumors) 1.1 criteria (TLGRECIST). We also investigated the clinical characteristics in relation to OS and EGFR mutation status. RESULTS: In EGFR mutation-positive patients, neither the clinical characteristics nor F-FDG PET/CT-derived parameters were significantly associated with OS. In contrast, univariate analysis identified male sex, a positive history of smoking, and TLGRECIST greater than or equal to 412 g as adverse prognostic factors for OS in EGFR mutation-negative patients. After adjustment for potential confounders in multivariate analysis, TLGRECIST was the sole independent predictor of OS in this subgroup. CONCLUSIONS: TLG determined per RECIST 1.1 criteria is an independent predictor of OS in EGFR mutation-negative patients with advanced lung adenocarcinoma. Further studies are needed to investigate whether this parameter may be a promising tool for stratifying such patients for risk-adapted therapies.

Positive clinical impact of an additional PET/CT scan before adjuvant radiotherapy or concurrent chemoradiotherapy in patients with advanced oral cavity squamous cell carcinoma.

UNLABELLED: The aim of this single-center study was to investigate whether obtaining an additional PET/CT scan before adjuvant radiotherapy or concurrent chemoradiotherapy (CCRT) could meaningfully improve 2-y disease-free survival (DFS) and disease-specific survival (DSS) rates. METHODS: Six hundred seventy-four patients with oral cavity squamous cell carcinoma who received adjuvant therapy after radical surgery were included. Of these, 152 patients were initially scheduled to receive an additional preradiotherapy/CCRT PET/CT scan within 1 wk of starting adjuvant therapy. However, 16 patients were excluded because of either medical problems or refusal. Therefore, 136 patients underwent a preradiotherapy/CCRT PET/CT scan (PET group), and 522 did not (NO-PET group). All of the participants were followed up for at least 2 y or censored at the last follow-up. The impact of preradiotherapy/CCRT PET/CT imaging was examined using Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Two-year DFS (80% vs. 70%, P = 0.033) and DSS (84% vs. 75%, P = 0.010) rates were significantly higher in the PET than in the NO-PET group. In the PET group, both DFS and DSS were higher in patients with negative findings than in those without (88% vs. 22% and 91% vs. 36%, respectively; both P < 0.001). A prognostic scoring system based on the presence of the 2 independent risk factors in the PET group (extracapsular spread and lymphatic invasion) predicted both DFS (P = 0.001 and P < 0.001, respectively) and DSS (P = 0.001 and P < 0.001, respectively). Nineteen patients (14%) had their treatment modified by preradiotherapy/CCRT PET/CT findings. Of these, 15 were treated with curative intent due to the presence of locoregional disease, and 4 received palliative care due to distant metastases. Seven of the 15 patients are currently alive without disease. CONCLUSION: An additional preradiotherapy/CCRT PET/CT scan improves both DFS and DSS in patients with advanced oral cavity squamous cell carcinoma.

Development and evaluation of an open-source software package "CGITA" for quantifying tumor heterogeneity with molecular images.

BACKGROUND: The quantification of tumor heterogeneity with molecular images, by analyzing the local or global variation in the spatial arrangements of pixel intensity with texture analysis, possesses a great clinical potential for treatment planning and prognosis. To address the lack of available software for computing the tumor heterogeneity on the public domain, we develop a software package, namely, Chang-Gung Image Texture Analysis (CGITA) toolbox, and provide it to the research community as a free, open-source project. METHODS: With a user-friendly graphical interface, CGITA provides users with an easy way to compute more than seventy heterogeneity indices. To test and demonstrate the usefulness of CGITA, we used a small cohort of eighteen locally advanced oral cavity (ORC) cancer patients treated with definitive radiotherapies. RESULTS: In our case study of ORC data, we found that more than ten of the current implemented heterogeneity indices outperformed SUVmean for outcome prediction in the ROC analysis with a higher area under curve (AUC). Heterogeneity indices provide a better area under the curve up to 0.9 than the SUVmean and TLG (0.6 and 0.52, resp.). CONCLUSIONS: CGITA is a free and open-source software package to quantify tumor heterogeneity from molecular images. CGITA is available for free for academic use at http://code.google.com/p/cgita.

Clinical outcomes of patients with oral cavity squamous cell carcinoma and retropharyngeal lymph node metastasis identified by FDG PET/CT.

PURPOSE: Retropharyngeal lymph node (RPLN) metastasis is an uncommon finding in patients with oral cavity squamous carcinoma (OSCC). We sought to investigate the clinical outcomes, clinicopathological characteristics, and the priority of treatment with curative intent in OSCC patients with RPLN involvement. METHODS AND MATERIALS: Between January 2007 and January 2011, we identified 36 patients with primary RPLN metastases (n = 10) or RPLN relapse (n = 26). The follow-up continued until June 2013. Disease-specific survival (DSS), disease-free survival (DFS), and the potential benefits of salvage therapy served as the main outcome measures. RESULTS: The 2-year DSS and DFS rates of untreated patients with RPLN involvement were 20% and 24%, respectively. Level IV/V neck lymph node involvement was an adverse prognostic factor for DSS (P = 0.048) and DFS (P = 0.018). All of the patients presenting with neck lymph node involvement at level IV/V died within 6 months. Among patients who were treated for RPLN relapse, the 2-year DSS and DFS rates from the relapse day were 12.8% and 9.6%, respectively. Concomitant contralateral neck lymph node metastases (N2c) were associated with lower 2-year DSS (P = 0.005) and DFS (P = 0.011) rates. Moreover, five (55%) of the nine patients with recurrent disease in the contralateral RPLN had distant metastases within 6 months. Salvage therapy yielded the maximum survival benefit in patients without N2c disease and ipsilateral RPLN involvement alone (P = 0.005). CONCLUSION: OSCC patients with RPLN involvement have poor outcomes. The risk factor for definitive treatment in OSCC patients with FDG PET/CT defined RPLN disease in primary disease was neck lymph node involvement at level IV/V and N2c and/or contralateral RPLN disease in recurrent disease. Treatment efforts with curative intent should be tailored according to individual risk factors.