Repeatability and reproducibility study of radiomic features on a phantom and human cohort.

The repeatability and reproducibility of radiomic features extracted from CT scans need to be investigated to evaluate the temporal stability of imaging features with respect to a controlled scenario (test-retest), as well as their dependence on acquisition parameters such as slice thickness, or tube current. Only robust and stable features should be used in prognostication/prediction models to improve generalizability across multiple institutions. In this study, we investigated the repeatability and reproducibility of radiomic features with respect to three different scanners, variable slice thickness, tube current, and use of intravenous (IV) contrast medium, combining phantom studies and human subjects with non-small cell lung cancer. In all, half of the radiomic features showed good repeatability (ICC > 0.9) independent of scanner model. Within acquisition protocols, changes in slice thickness was associated with poorer reproducibility compared to the use of IV contrast. Broad feature classes exhibit different behaviors, with only few features appearing to be the most stable. 108 features presented both good repeatability and reproducibility in all the experiments, most of them being wavelet and Laplacian of Gaussian features.

Invasion of the mandible in gingivobuccal complex cancers: Histopathological analysis of routes of tumour entry and correlation with preoperative assessment.

OBJECTIVES: To determine the most accurate imaging modality predicting mandibular invasion in gingivobuccal (GB) complex cancers. To determine patterns of invasion and routes of tumour entry into the mandible by detailed histopathologic analysis. MATERIAL AND METHODS: Prospective observational study of GB Complex cancers juxtaposed with the mandible clinically necessitating some form of mandibular resection. Orthopantomogram (OPG), Multi Detector Computed Tomography (MDCT), DENTA scan and Single Photon Emission Computed Tomography scan (SPECT) were performed after which the patient was subjected to surgery. Histopathological assessment was systematically performed with serial cuts of the mandibular segment. RESULTS: Of 70 patients, MDCT was the most accurate with area under curve (AUC) of 0.833. OPG, DENTA and SPECT had AUC of 0.714, 0.786 and 0.738 respectively. Mean calculated difference of involved height was -0.025 cm by MDCT (p value 0.87), -0.2 cm by OPG (p value 0.09) and 0.12 by DENTA scan (p value 0.41). Mean difference of involved length was -0.51 cm (p value 0.08) and -1.02 cm (p value 0.04) for MDCT and OPG respectively. 50% of tumour invasion was through the occlusal route while large tumours demonstrated multiple routes of entry. CONCLUSION: -Gingivobuccal complex cancers are homogenous with respect to mandibular invasion, preferred route of tumour entry being the occlusal surface. -Multidetector CT scan is fairly accurate in detecting mandibular involvement and predicting extent of involvement. -Oncological safety can be achieved by positioning the bone cuts corresponding to the adjacent soft tissue margins in segmental mandibulectomy.

Applying the QUARTZ Trial Results in Clinical Practice: Development of a Prognostic Model Predicting Poor Outcomes for Non-small Cell Lung Cancers with Brain Metastases.

AIMS: The role of whole brain radiotherapy (WBRT) in patients with brain metastases from non-small cell lung cancers (NSCLC) has been questioned. However, no reliable criteria exist to identify patients who do not benefit from WBRT. The objective of the current study was to develop a prognostic model to identify such patients whose survival matches that of the Quality of Life after Treatment for Brain Metastases (QUARTZ) study. MATERIALS AND METHODS: Outcome data of patients with NSCLC with brain metastases undergoing WBRT enrolled in a prospective observational study in a tertiary cancer centre were used to develop a prognostic model. Baseline clinico-radiological factors were used for development of the model. The model was internally validated and calibration accuracy was checked for prediction of 70 day mortality. The generated prognostic model was presented as a nomogram. RESULTS: The median overall survival of 140 patients enrolled in the study was 166 days (95% confidence interval 108-242 days). The prognostic model identified gender, Karnofsky performance status and epidermal growth factor receptor activating mutation status as significant factors influencing overall survival. The model showed a modest discriminative ability with an optimism-corrected C-index of 0.64. However, model calibration error did reveal a moderate degree of calibration error. The high-risk subgroup identified by the model had a median overall survival of 67 days (95% confidence interval 56-101 days), which was similar to that observed in the QUARTZ trial. CONCLUSION: This prognostic model derived from traditional clinico-radiological features had a modest ability to identify patients with poor prognosis who may not benefit from WBRT. However, the high-risk subgroup identified using this prognostic model had a survival similar to that observed for patients in the QUARTZ trial.

A prospective study of telephonic contact and subsequent physical follow-up of radically treated lung cancer patients.

BACKGROUND: We tested the hypothesis that telephonic follow-up (FU) may offer a convenient and equivalent alternative to physical FU of radically treated lung cancer patients. DESIGN: Prospective study carried out at a tertiary referral cancer care institute, Mumbai. MATERIALS AND METHODS: Two hundred consecutive lung cancer patients treated with curative intent were followed up regularly with telephonic interviews paired with their routine physical FU visits. Patient satisfaction with the telephonic call and the physical visit, the anxiety level of the patient after meeting the physician and the economic burden of the visit to the patient were noted in a descriptive manner. Kappa statistics was used to assess concurrence between the telephonic and physical impression of disease status. RESULTS: With a median FU duration of 21.5 months, the median satisfaction scores for telephonic and physical FU were 8 and 9, respectively. The prevalence and bias adjusted kappa (PABAK) score of the entire cohort of patients was 0.64 (95% confidence interval [CI] =0.58-0.70). Data analyzed up to first disease progression/relapse on FU had a PABAK score of 0.71 (95% CI = 0.64-0.77) indicating substantial agreement. Patients with disease controlled at the FU had a significant PABAK score of 0.88 (95% CI = 0.80-0.94) indicating excellent concurrence. On average, each patient spent Rs. 5117.10 on travel and Rs. 3079.06 on lodging per FU visit. CONCLUSION: Telephonic FU is substantially accurate in assessing disease status until the first relapse. In a resource-constrained country like India, it is worthwhile to further explore the benefits of such an alternative strategy.

Solitary pulmonary nodule evaluation in regions endemic for infectious diseases: Do regional variations impact the effectiveness of fluorodeoxyglucose positron emission tomography/computed tomography.

BACKGROUND: Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) has become a preferred imaging modality for the evaluation of solitary pulmonary nodule (SPN), particularly in the developed world. Since FDG can concentrate in infective/inflammatory lesions, the diagnostic utility of FDG-PET can be questioned, particularly in regions endemic for infectious decisions. AIM: To evaluate the accuracy of FDG-PET/CT in evaluation of SPNs in a population endemic for infectious disease and to assess if regional variations have an impact on its effectiveness. MATERIALS AND METHODS: All patients who underwent an FDG/PET-CT with a clinico-radiological diagnosis of SPN categorized as indeterminate were included. Based on a maximum standardized uptake values (SUVmax) cut-off of 2.5, lesions were classified as benign (<2.5) or malignant (>2.5) and compared with gold standard histopathology. The diagnostic accuracy of PET-CT to detect malignancy was calculated. On the basis of final histopathology, lesions were grouped as (a) malignant nodules (b) infective/granulomatous nodules with a specific diagnosis and (c) nonspecific inflammatory nodules. The SUVmaxbetween these groups was compared using nonparametric statistical tests. RESULTS: A total of 191 patients (129 males, 62 females) with a median age of 64 years (range: 36-83) were included. Totally, 144 nodules (75.3%) were malignant and 47 were benign (24.7%). Adenocarcinoma (n = 84) was the most common malignancy. Tuberculosis (n = 16) and nonspecific infections (n = 24) were the two most common benign pathologies. There was a significant overlap in the metabolic uptake of malignant (median SUVmax-11.2, range: 3.3-34.6) and tuberculous nodules (median SUVmax-10.3, range: 2.7-22.5) with no statistically difference between their SUVmaxvalues (P = 0.43). The false-positive rate was 65.2% and the false-negative rate was 5.5%. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FDG-PET/CT for detecting malignancy were 94.4%, 34.7%, 81.9%, 66.6%, and 79.5%, respectively. CONCLUSIONS: Though FDG-PET scans show a very high sensitivity for malignant nodules, it has a high false-positive rate and reduced specificity when characterizing SPNs in an infectious endemic region. Physicians must be aware of this limitation in the workup of lung nodules, and regional variations must be considered before further management decisions are taken.

The duration of gonadotropin stimulation does not alter the clinical pregnancy rate in IVF or ICSI cycles.

BACKGROUND: Ovarian stimulation is an essential part of assisted reproduction treatments. Research on whether the duration of stimulation alters the success in assisted reproduction has not been conclusive. AIM: The purpose of the study was to establish whether the duration of ovarian stimulation alters the success in assisted reproduction treatments. METHODS: All fresh (non-donor) stimulation cycles performed in an academic tertiary referral ART centre over a period of 18 years, between 1st January 1997 and 31st December 2014, were identified. Data were prospectively and electronically collected. IVF and ICSI cycles were analysed independently. Each category was then subdivided into assisted reproduction cycles where the antagonist, long (down regulation) and flare protocol were used. Clinical pregnancy was the main outcome measured. A total of 10,478 stimulation cycles (6011 fresh IVF and 4467 fresh ICSI) reaching egg collection were included. RESULTS: We showed no significant difference in CP rates in IVF cycles for the long (p = 0.082), antagonist (p = 0.217) or flare (p = 0.741) protocol cycles or in ICSI cycles with the long (p = 0.223), antagonist (p = 0.766) or the flare (p = 0.690) protocol with regards the duration of stimulation. CONCLUSION: The duration of stimulation does not alter the CP rate in ICSI or IVF cycles using the long, antagonist or flare stimulation protocol.

Optimizing treatment and analysis of prognostic factors for locally advanced nonsmall cell lung cancer in resource-limited population.

BACKGROUND: Lung cancer most commonly presents in advanced stages in developing countries, where combined modality treatment using chemo-radiotherapy (CTRT) is the standard of care. MATERIALS AND METHODS: A retrospective audit of patients of nonsmall cell lung cancer (NSCLC) treated at a single Institute from January 2008 to December 2012 was conducted. Various prognostic factors affecting disease-free survival (DFS) and overall survival (OS) were studied by univariate and multivariate analysis. All patients were meticulously followed-up clinically and telephonic contacts. RESULTS: Overall 171 patients of NSCLC were treated with definitive CTRT using concurrent chemotherapy in 66% patients and sequential therapy in 28% patients. The actuarial 2 years DFS was 17.5% and 2 years OS was 61.5%. Complete response to treatment resulted in significantly better DFS and OS. Definitive CTRT was very well-tolerated in these patients with good compliance. CONCLUSION: Definitive CTRT, sequence being individualized depending on performance status and disease stage at presentation, is a feasible and effective treatment modality for locally advanced NSCLC patients in the developing world. Response to treatment is an important prognostic factor for treatment outcomes.

Positron emission tomography thyroid incidentaloma: Is it different in Indian subcontinent?

BACKGROUND: Positron emission tomography (PET) forms an integral part in work-up and follow-up of various malignancies. With the increased use of PET in oncology, finding of an incidental focal thyroid uptake (incidentaloma) is not unusual and presents a diagnostic challenge. AIM: The aim of the following study is to evaluate the frequency and radio-pathologic correlation of focal 18-fluoro deoxyglucose uptake (FDG) on PET within the thyroid from a large series. MATERIALS AND METHODS: Retrospective review of 37,000 consecutive patients who underwent FDG-PET at tertiary cancer center in India. Radiological, pathological, PET scan and follow-up details were evaluated. Statistical analyzes were carried out using Mann Whitney test and Pearson correlation. RESULTS: Abnormal thyroid uptake was seen in 78 (0.2%) patients. Nearly 61 (0.16%) scans had focal and 17 (0.04%) had diffuse FDG uptake. A total of 57 patients with focal uptake were available for further evaluation. No further evaluation was done in 24 (42.1%) patients who had advanced index malignancy. Of the remaining 33 patients 26 were benign and seven were a cause for concern (four primary thyroid cancers, one follicular neoplasm with hurthle cell change and two metastatic cancers). There was no significant correlation in Standardized uptake value (SUV) max of benign and malignant lesion (P = 0.5 on Mann Whitney) or size (r = 0.087 Pearson correlation co-efficient P= 0.667). CONCLUSION: Incidence of PET incidentaloma is low in this large cohort of Indian patients. Nearly 27% of focal incidentaloma were malignant. There was no correlation between the SUVmax, size and malignancy.

Thymic epithelial tumors: Can fluorodeoxyglucose positron emission tomography help in predicting histologic type and stage?

OBJECTIVES: To study the utility of fluorodeoxyglucose (FDG) positron emission tomography (PET) in predicting (1) the World Health Organization (WHO) histologic type and differentiating low-risk from high-risk types. (2) Tumor stage and differentiate early from advanced stage disease. MATERIALS AND METHODS: Patients with thymic epithelial neoplasia who underwent a pretreatment FDG-PET study were included. Tumor maximum standardized uptake value (SUVmax) was correlated with the WHO histologic type and also with the Masaoka-Koga (MK) staging system. Patients with WHO Type A, AB, and B1 were classified as low risk and those with B2 and B3 as high risk. Thymic carcinomas belonged to Type C. Patients with MK Stage I and II disease were grouped as early stage and those with Stage III and IV as an advanced stage. Differences in SUVmax between the various groups were calculated. RESULTS: The SUVmax of thymic carcinomas was significantly higher as compared to low-risk (P = 0.001) and high-risk groups (P = 0.007). The SUVmax of high-risk group was also significantly higher than the low-risk group (P = 0.002). SUVmax cutoff of 6.5 was able to differentiate thymic carcinomas from thymomas with 100% sensitivity and 87.2% specificity. The SUVmax in patients with advanced stage disease showed a higher trend compared to those with early stage, but the difference was not significant (P = 0.167). CONCLUSION: PET can differentiate thymic carcinomas from rest of the thymoma subtypes by the virtue of their higher FDG uptake. It can also provide valuable information in differentiating high-risk from low-risk thymomas and in predicting disease stage.

Metronomic weekly paclitaxel in advanced unresectable esophageal cancer.

CONTEXT: Advanced esophageal cancer is aggressive with an expected median survival of 6-7 months. Combination chemotherapy regimens provide effective palliation, but result in substantial toxicity. MATERIALS AND METHODS: Retrospective analysis of prospectively collected data of patients with advanced esophageal cancer, not amenable to definitive intent therapy who were treated with intravenous weekly paclitaxel. RESULTS: Between October 2010 and August 2011, 51 patients were included. Median age was 56 years, with a male: female ratio of 2.9:1. 29% were mid esophageal and 55% were lower third and gastroesophageal junction tumors. 65% of the tumors had squamous histology. Performance status was > 2 in 45%. 61% patients had received prior therapy, either definitive or palliative. 51% patients were platinum-pre-treated and 29% had received prior 3 weekly paclitaxel. 76% patients had distant metastases. Median number of cycles of weekly paclitaxel delivered was 11. 71% of patients had improvement in dysphagia, with a median time to symptom improvement of 9 days. In 72% patients, the feeding nasogastric tube could be removed. Overall response rate was 49% (complete remission: 4%, partial remission: 45%, stable disease: 13%). Median progression free survival was 4.7 months (confidence interval [95% CI: 3.7-5.7 months]) and median overall survival was 7.5 months (95% CI: 3.1-11.8 months). Histopathology, performance status and pre-treatment albumin significantly affected survival. The most common grade 3/4 toxicities included hyponatremia (14%), fatigue (16%), diarrhea (12%), anemia (31%), neutropenia (10%) and febrile neutropenia (4%). CONCLUSIONS: Metronomic weekly paclitaxel chemotherapy may provide palliative benefit in advanced unresectable metastatic esophageal cancer with minimal toxicity.

Grieving after early pregnancy loss--a common reality.

A miscarriage can be very traumatic for a couple and their immediate family. The aim of this study was to assess, using the Perinatal Grief Scale (PGS), whether the type of early pregnancy loss influences the severity of grief and whether the presence of living children influences the severity of grief. Over a period of 6 months in 2008, seventy five patients were recruited for the study, of which 7 (9.3%) had molar pregnancies, 20 (26.7%) had ectopic pregnancies, 43 (573%) had a miscarriage and 5 (6.7%) had recurrent miscarriages. In this study there was no significant difference in severity of grief, between women that had a miscarriage and ectopic pregnancy (p = 0.14) or, between women that had a miscarriage and a molar pregnancy (p = 0.85). Women who had experienced a ectopic pregnancy did not have a higher grief intensity than the women that had a molar pregnancy (p = 0.75). However, for women with a child, the grief intensity significantly increases with the number of miscarriages (p = 0.015). Women with no children with an ectopic pregnancy grieve significantly more than those with a child (p = 0.019). An appointment for the 'Miscarriage Clinic' should be offered to all of these women but special attention should be paid to those in the categories most at risk

Perinatal outcome after ultrasound diagnosis of anhydramnios at term.

The aim was to assess the maternal and fetal outcome in women who had labour induced for anhydramnios after 37 completed weeks of gestation. A retrospective study was conducted at the Rotunda Hospital from 1 January 2003 to 31 December 2007. All women with anhydramnios at term were identified from a review of ViewPoint® (computer software for antenatal scans performed), hospital data and the labour ward register. All women with a history of previous lower segment caesarean section (LSCS), current significant medical illness such as diabetes, hypertension, pre-eclampsia or ruptured membranes were excluded because the aim of the study was to focus specifically on low risk pregnancies with an incidental diagnosis of anhydramnios after 37 weeks' gestation. The maternal and fetal outcome parameters reviewed included: maternal age, parity, gestation, method of induction, mode of delivery, Apgar score and the requirement for obstetric or neonatal intervention. This study showed that anhydramnios is associated with a 56.6% LSCS rate in primigravida and a 19.0% LSCS rate in multigravida. Our study did not show any significant neonatal morbidity and there were no cases of mortality.

Utility of PET in unknown primary with cervical metastasis: a retrospective study.

BACKGROUND: FDG-PET is recommended as an investigation in unknown primary tumors, but its definitive role and cost effectiveness are yet to be established. AIMS: dditional value of FDG-PET over conventional imaging in unknown primary tumors with cervical metastasis. SETTING AND DESIGN: Retrospective study in a tertiary level oncology centre. MATERIALS AND METHODS: A total of 112 patients were divided into three groups; 53 with conventional modalities (either computed tomography or magnetic resonance imaging) (group I), 59 with FDG-PET (group II), and group III (subgroup of group II) with both (40 patients). STATISTICAL ANALYSIS: Sensitivity and specificity of both conventional modality and PET were calculated. Association between neck nodes and distant metastasis was analysed using multivariate logistic regression analysis. RESULTS: Sensitivity and specificity for conventional modalities was 92.3% and 50% and sensitivity and specificity of FDG-PET was 92.8% and 71.4%, respectively. FDG-PET detected metastasis in 52.54% of patients. Multivariate logistic regression analysis showed statistically significant association between distant metastasis and multiplicity of nodes (N2b, N2c) (P = 0.007). Among all patients with low neck nodes in group II, FDG-PET detected primaries in 12 patients, 9 of which were infraclavicular (75%). FDG-PET added information to conventional imaging in 32.5% of patients and influenced an overall change in management in 38.9% of patients. CONCLUSIONS: FDG-PET is a valuable tool influencing change of management in unknown primary with cervical metastasis. It is recommended especially in the presence of low or multiple neck nodes in view of high incidence of infraclavicular primary and distant metastasis, respectively.

Isolated left innominate vein aneurysm: a rare cause of mediastinal widening.

Mediastinal widening in an adult is mostly nodal in origin. Occasionally vascular aneurysms may be the underlying cause, in which case the aorta or its branches are most frequently involved. Thoracic venous aneurysms, on the other hand, have been reported only in anecdotes, with fusiform aneurysm of the superior vena cava being the commonest. Isolated aneurysms involving the brachiocephalic/innominate vein are extremely rare. We describe detection of a saccular aneurysm of the innominate vein, as the underlying cause of mediastinal widening seen on a chest radiograph in a 42-year-old asymptomatic woman. The characteristic radiological findings of thoracic venous aneurysms are described with particular reference to the importance of multiplanar computed tomography in such settings. Also discussed is the role of imaging in the diagnosis and guiding the management of this rare entity.

Depressive symptom clusters are differentially associated with atherosclerotic disease.

BACKGROUND: Depression increases the risk of subsequent vascular events in both cardiac and non-cardiac patients. Atherosclerosis, the underlying process leading to vascular events, has been associated with depression. This association, however, may be confounded by the somatic-affective symptoms being a consequence of cardiovascular disease. While taking into account the differentiation between somatic-affective and cognitive-affective symptoms of depression, we examined the association between depression and atherosclerosis in a community-based sample. METHOD: In 1261 participants of the Nijmegen Biomedical Study (NBS), aged 50-70 years and free of stroke and dementia, we measured the intima-media thickness (IMT) of the carotid artery as a measure of atherosclerosis and we assessed depressive symptoms using the Beck Depression Inventory (BDI). Principal components analysis (PCA) of the BDI items yielded two factors, representing a cognitive-affective and a somatic-affective symptom cluster. While correcting for confounders, we used separate multiple regression analyses to test the BDI sum score and both depression symptom clusters. RESULTS: We found a significant correlation between the BDI sum score and the IMT. Cognitive-affective, but not somatic-affective, symptoms were also associated with the IMT. When we stratified for coronary artery disease (CAD), the somatic-affective symptom cluster correlated significantly with depression in both patients with and patients without CAD. CONCLUSIONS: The association between depressive symptoms and atherosclerosis is explained by the somatic-affective symptom cluster of depression. Subclinical vascular disease thus may inflate depressive symptom scores and may explain why treatment of depression in cardiac patients hardly affects vascular outcome.