Early Detection of Secondary Central Nervous System Lymphoma on PET/CT.

We present a case of secondary central nervous system relapse of lymphoma detected initially on PET/CT without corresponding findings on MRI. A 60-year-old lymphoma patient demonstrated an FDG-avid focus in left cerebellar hemisphere on restaging PET/CT. MRI brain showed no corresponding abnormality, and expectant management ensued. Six months later, she represented with metabolic progression of previously seen FDG-avid focus in left cerebellar hemisphere, now also manifesting as an enhancing mass on MRI. Posttreatment scan for presumed lymphoma relapse showed metabolic response. This case demonstrates the advantage of PET/CT over anatomical imaging to detect metabolic changes before structural changes become apparent.

Successful therapeutic rechallenge after a severe episode of high dose methotrexate-induced choreoathetosis: A case report.

Methotrexate (MTX) is an essential chemotherapy drug used in the treatment of malignancies, but it is known to cause complications to the central nervous system. We report a case of severe MTX neurotoxicity in an adult presenting with choreoathetosis despite a normal clearance of MTX. High dose-MTX has been successfully rechallenged without any neurological sequelae. We reviewed the relevant literature of similar manifestations and summarized their clinical data, magnetic resonance imaging features and treatment given. None of them has recurrence of neurotoxicity. We concluded that it is safe to persist with MTX even after a previous episode of toxic leukoencephalopathy.

Clinical and dosimetric predictors of physician and patient reported xerostomia following intensity modulated radiotherapy for nasopharyngeal cancer - A prospective cohort analysis.

BACKGROUND AND PURPOSE: To compare physician and patient reported xerostomia and correlate xerostomia with dosimetric and clinical parameters for nasopharyngeal cancer (NPC) patients treated with intensity modulated radiotherapy (IMRT) and chemotherapy. PATIENTS AND METHODS: We analyzed the data of 172 patients with locally advanced NPC. Xerostomia was evaluated via physician-rated xerostomia based on RTOG morbidity score (E1), patient-rated dry mouth (E2) and patient-rated sticky saliva (E3) based on EORTC QLQ-HN35 questionnaire. Primary endpoint was the presence of moderate to severe xerostomia at 2-year after completion of IMRT. RESULTS: The levels of physician reported xerostomia (E1) were consistently lower than patient reported dry mouth (E2) over time. The incidence of patients with xerostomia at 3-month post RT was 58% based on E1, 70% based on E2, and 51% based on E3. The corresponding incidence rates at 2-year post RT was 26% (E1), 36% (E2) and 21% (E3). The incidence of patients with xerostomia at 1-year post RT was close to that at 2-year post RT for all the 3 endpoints. The average Dmean of parotid glands was 41.5 Gy (range: 31.0 Gy-65.9 Gy, median: 40.7 Gy). No dosimetric parameters were significantly associated with xerostomia. CONCLUSION: Significant proportion of patients still experienced long term xerostomia with IMRT. Dose-effect relationships between xerostomia and the parotid glands were not observed in this study.

Autophagy Governs Protumorigenic Effects of Mitotic Slippage-induced Senescence.

The most commonly utilized class of chemotherapeutic agents administered as a first-line therapy are antimitotic drugs; however, their clinical success is often impeded by chemoresistance and disease relapse. Hence, a better understanding of the cellular pathways underlying escape from cell death is critical. Mitotic slippage describes the cellular process where cells exit antimitotic drug-enforced mitotic arrest and "slip" into interphase without proper chromosome segregation and cytokinesis. The current report explores the cell fate consequence following mitotic slippage and assesses a major outcome following treatment with many chemotherapies, therapy-induced senescence. It was found that cells postslippage entered senescence and could impart the senescence-associated secretory phenotype (SASP). SASP factor production elicited paracrine protumorigenic effects, such as migration, invasion, and vascularization. Both senescence and SASP factor development were found to be dependent on autophagy. Autophagy induction during mitotic slippage involved the autophagy activator AMPK and endoplasmic reticulum stress response protein PERK. Pharmacologic inhibition of autophagy or silencing of autophagy-related ATG5 led to a bypass of G1 arrest senescence, reduced SASP-associated paracrine tumorigenic effects, and increased DNA damage after S-phase entry with a concomitant increase in apoptosis. Consistent with this, the autophagy inhibitor chloroquine and microtubule-stabilizing drug paclitaxel synergistically inhibited tumor growth in mice. Sensitivity to this combinatorial treatment was dependent on p53 status, an important factor to consider before treatment.Implications: Clinical regimens targeting senescence and SASP could provide a potential effective combinatorial strategy with antimitotic drugs. Mol Cancer Res; 16(11); 1625-40. ©2018 AACR.

Focal Therapy for Prostate Cancer with In-Bore MR-guided Focused Ultrasound: Two-Year Follow-up of a Phase I Trial-Complications and Functional Outcomes.

Purpose To report the safety profile and 2-year functional outcomes of in-bore magnetic resonance (MR)-guided focused ultrasound on single cancer foci in men with prostate cancer. Materials and Methods Ethics approval was obtained from the centralized institutional review board for this prospective single-arm study, and patients provided informed consent. Patients with untreated low-volume low-grade prostate cancer (clinical stage T2a or lower; Gleason score, 3+3; index tumor ≤10 mm3) underwent MR-guided focused ultrasound between July 2011 and February 2013. All patients underwent robotic transperineal mapping biopsy and multiparametric MR imaging. Only those with a maximum of two lesions smaller than 10 mm at mapping biopsy were included. Target areas were sonicated with real-time MR thermometry monitoring, excluding critical areas from the beam path. Serum prostate-specific antigen (PSA) and Expanded Prostate Index Composite (EPIC) scores were obtained at baseline and at 1, 3, 6, 12, 18, and 24 months and were plotted to observe their trend. Mean EPIC subdomain score changes at each serial time point were compared with the baseline score by using paired t tests (level of significance, P < .007). Repeat transperineal biopsy was performed at 6 and 24 months. Results Fourteen men (mean age, 62.8 years; median PSA level, 8.3 ng/mL) underwent treatment, with 12 men completing 2-year follow-up. A median reduction of PSA level by 2.9 ng/mL was observed at 6 months. Seven men had Clavien-Dindo grade 1-2 complications. There was a slight insignificant deterioration of EPIC urinary symptom score (mean increase of 7.8 points compared with baseline, P = .012) noted at 1 month, but it returned to baseline by 3 months. There was a trend to deterioration in sexual function score (mean decrease, 4.4 points; P = .04 [not significant]) that normalized at 3 months. There was no significant change in EPIC subdomain scores from baseline over the 24 months. At 6-month template biopsy, one man had cancer with a Gleason score greater than 6; at 24 months, three men had cancer with a Gleason score greater than 6. Conclusion MR-guided focused ultrasound is technically feasible for focal prostate ablation and appears to have a favorable early safety and functional profile. Further clinical trials are necessary to establish oncologic efficacy. © RSNA, 2017 Online supplemental material is available for this article.

Intravoxel incoherent imaging of renal fibrosis induced in a murine model of unilateral ureteral obstruction.

PURPOSE: To evaluate non-invasive imaging biomarkers for assessing renal fibrosis. DWI is used to assess renal function; intravoxel incoherent motion (IVIM) provides additional measures of perfusion-related diffusion (D*, blood flow; f, perfusion fraction). We aim to determine if reduced ADC seen in renal fibrosis is attributable to perfusion-related diffusion changes or to known reduction in tissue diffusivity (D). MATERIALS AND METHODS: Unilateral ureteral obstruction (UUO) was created in six mice to induce renal fibrosis. DWI was performed the day before and 7 days post-UUO. A range of b-values from 0 to 1200 s/mm(2) were used. IVIM parameters were obtained using region of interests drawn over the renal parenchyma. Histopathological analysis of both kidneys was performed in all mice. Results were analyzed using the paired t-test with P<0.05 considered statistically significant. RESULTS: D and f were significantly lower in the ligated kidneys at Day 7 compared to before ligation and no significant difference was found for D*. Comparing non-ligated and ligated kidneys within the same mouse at Day 7, significantly lower D values were observed in the ligated kidneys, while no significant difference was found for f and D*, although the values of f were generally lower. Histopathological analysis confirmed development of fibrosis and reduction in glomeruli in all the ligated kidneys at Day 7. CONCLUSION: Our study shows that the reduction in ADC seen in renal fibrosis is attributable not only to reduced D as previously encountered but also a decrease in vascularity as assessed by f. Reduction in f is possibly related to a reduction in glomeruli.

Indication of lower neck irradiation in nasopharyngeal carcinoma without nodal metastasis: the potential impact of tumor volume.

BACKGROUND: Elective radiation of lower neck is controversial for nasopharyngeal carcinoma (NPC) without lymph node metastasis (N0 disease). Tumor volume is an important prognostic indicator. The objective of this study is to explore the potential impact of tumor volume on the indication of the lower neck irradiation for N0-NPC, by a qualitative evaluation of the relationship between tumor volume and nodal metastasis. METHODS: Magnetic resonance (MR) images of 99 consecutive patients with NPC who underwent treatment were retrospectively reviewed. Primary tumor volumes of NPC were semi-automatically measured, nodal metastases were N-classified and neck level involvements were examined. Distributions of tumor volumes among N-category-based groups and distributions of N-categories among tumor volume-based groups were analyzed, respectively. RESULTS: The numbers of patients with N0 to N3 disease were 12, 39, 32, and 16, respectively. The volumes of primary tumor were from 3.3 to 89.6 ml, with a median of 17.1 ml. For patients with nodal metastasis, tumor volume did not increase significantly with the advancing of N-category (P > 0.05). No significant difference was found for the distribution of N1, N2, and N3 categories among tumor volume-based groups (P > 0.05). Nevertheless patients with nodal metastasis had significantly larger tumor volumes than those without metastasis (P < 0.05). Patients with larger tumor volumes were associated with an increased incidence of nodal metastasis. CONCLUSIONS: Certain positive correlations existed between tumor volume and the presence of nodal metastasis. The tumor volume (>10 ml) is a potential indicator for the lower neck irradiation for N0-NPC.

Reversible recurrent laryngeal nerve palsy in acute thyroiditis.

First reported by Nager in 1927, unilateral vocal cord paralysis associated with thyroid disease suggests the malignant and irreversible nature of the thyroid lesion. This condition is rarely seen in benign thyroid diseases, and the function of the vocal cord does not usually return. We present a 54-year-old woman with a history of right hemithyroidectomy for benign thyroid nodule, who had an episode of subacute thyroiditis associated with unilateral vocal cord paralysis. The patient was treated with intravenous antibiotics and underwent a completion thyroidectomy. Post operation, her vocal cord function recovered successfully. Unilateral vocal cord paralysis can be seen in thyroiditis, and this can be reversed with steroids and antibiotics. If surgery is necessary, care must be taken to preserve the recurrent laryngeal nerve.

Deconvolution assessment of splenic and splanchnic contributions to portal venous blood flow in liver cirrhosis.

PURPOSE: To devise a noninvasive imaging method for resolving the relative contribution of splenic and splanchnic blood flow to portal venous flow and derive quantitative estimates for parameters pertaining to splenic and portal hemodynamics. METHODS: Tracer concentration-time curves of the aorta, portal vein, and spleen can be extracted from dynamic contrast-enhanced (DCE) CT or MR images. A combination of two tracer analysis approaches, namely arterial-venous sampling and residual tracer deconvolution, is proposed to model these concentration-time curves and derive hemodynamic parameters pertaining to splenic and portal circulation. Clinical feasibility of the proposed method was explored using DCE CT datasets of eight cirrhotic patients. Monte Carlo simulations were performed to evaluate the confidence of the parameter estimates. RESULTS: Portal blood flow was estimated to be 763.8 +/- 438.1 ml/min in cirrhotic patients and the splenic contribution was found to be elevated (0.75 +/- 0.22). Estimates of splenic blood flow (582 +/- 420 ml/min) and transit time (15.3 +/- 10.1 s) in cirrhotic patients were consistent with reported values obtained using duplex Doppler ultrasound and dynamic scintigraphy, respectively. CONCLUSIONS: This study shows the feasibility of noninvasive assessment of splenic and portal hemodynamic parameters by DCE imaging using a combination of tracer kinetics modeling techniques.

Management of the neck after chemoradiotherapy for head and neck cancers in Asia: consensus statement from the Asian Oncology Summit 2009.

The addition of a planned neck dissection after radiotherapy has traditionally been considered standard of care for patients with positive neck-nodal disease. With the acceptance of chemoradiotherapy as the new primary treatment for patients with locally advanced squamous-cell head and neck cancers, and the increasing numbers of patients who achieve a complete response, the role of planned neck dissection is now being questioned. The accuracy and availability of a physical examination or of different imaging modalities to identify true complete responses adds controversy to this issue. This consensus statement will address some of the controversies surrounding the role of neck dissection following chemoradiotherapy for squamous-cell carcinomas of the head and neck, with particular reference to patients in Asia.

Comparison of 4 modalities for distant metastasis staging in endemic nasopharyngeal carcinoma.

BACKGROUND: Endemic nasopharyngeal carcinoma (NPC) commonly metastasizes to the lungs, liver, and bones. This study aims to assess the efficacy of 4 distant metastasis staging modalities, namely (1) conventional work-up comprising chest X-ray, liver ultrasound, and skeletal scintigraphy, (2) CT of the thorax, abdomen, and skeletal scintigraphy, (3) (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET), and (4) integrated FDG-PET/CT. METHODS: Seventy-eight consecutive patients diagnosed with NPC were enrolled and followed up for a minimum of 6 months to confirm the staging at diagnosis. RESULTS: Six patients (7.7%) had distant metastases at diagnosis. The sensitivities and specificities of conventional work-up, combined CT and skeletal scintigraphy, FDG-PET, and FDG-PET/CT were 33.3%, 66.7%, 83.3%, and 83.3%; and 90.3%, 91.7%, 94.4%, and 97.2%, respectively. The corresponding accuracies were 85.9%, 89.7%, 93.6%, and 96.2%. CONCLUSIONS: FDG-PET/CT is the most sensitive, specific, and accurate modality for distant metastasis staging of endemic NPC.

Osteoradionecrosis of the cervical spine complicated by pneumocephalus and meningitis in a nasopharyngeal cancer patient radically treated with radiotherapy 11 years ago.

Superimposed infection of osteoradionecrotic cervical spine with cranial extension is difficult to treat and potentially fatal. This report describes the case of a middle-aged Chinese man 11 years post radical radiotherapy for nasopharyngeal cancer with no evidence of disease presenting initially with neck pain secondary to cervical osteoradionecrosis. He was re-admitted a month later with aspiration pneumonia associated with Streptococcus milleri bacteraemia, complicated by septic shock. The last re-admission was 2 months later with fever, expressive dysphasia and right upper motor neuron signs. There was interval increase of dental and peridental soft tissue mass, interval widening of atlantodental distance on MRI cervical spine associated with pneumocephalus, meningeal enhancement and pre-pontine soft tissue mass on CT brain consistent with infected osteoradionecrotic cervical spine complicated by cranial extension. The patient also had concomitant bilateral pneumonia and subsequently passed away from fulminant sepsis.

CT imaging of malignant metastatic hemangiopericytoma of the parotid gland with histopathological correlation.

We report an extremely rare case of malignant hemangiopericytoma (HPC) of the parotid gland and its metastatic spread to lung, liver, and skeletal muscle. Computed tomography (CT) imaging, histopathological and immunohistochemical methods were employed to study the features of malignant HPC and its metastases. CT imaging was helpful to determine the exact location, involvement of adjacent structures and vascularity, as well as evaluating pulmonary, hepatic, peritoneal, and muscular metastases. Immunohistochemical and histopatholgical features of the primary tumor as well as the metastases were consistent with the diagnosis of malignant HPC.

Independent component analysis of dynamic contrast-enhanced magnetic resonance images of breast carcinoma: a feasibility study.

PURPOSE: To study the possibility of using independent component analysis (ICA) to identify breast lesions as separate hemodynamic sources on dynamic contrast-enhanced (DCE) MR images, as depicted by the passage of contrast medium. MATERIALS AND METHODS: Six patients who were histopathologically confirmed with breast carcinoma underwent DCE MRI with 5 precontrast and 60 postcontrast scans at a time-resolution of 8 s. A spatial ICA algorithm was applied on the DCE MRI data set to extract spatial component maps corresponding to source locations with different signal time-intensity patterns. To verify the present hypothesis of the ability of ICA to reveal tumor voxels as a separate hemodynamic phase, tumor margins were outlined by an experienced radiologist who was blinded from the ICA results, and the manual outlines were compared with the ICA maps. RESULTS: Consistently for each of the six patient study cases, it was found that ICA yields a tumor component map associated with typical tumor enhancement patterns of rapid enhancement with washout or plateau. Tumor outlines manually drawn by the radiologist were in good agreement with the tumor locations depicted in the tumor component maps. CONCLUSION: ICA may provide an objective method for identifying the outlines of enhancing breast tumors on DCE MR images and to automatically extract the tumor signal intensity-time curve for subsequent tracer kinetics analysis.

Significance of tumour volume measurements in tongue cancer: a novel role in staging.

BACKGROUND: Tongue cancers are staged by the American Joint Committee on Cancer and the Union Internationale Contre le Cancer TNM staging systems. Cancer, however, evolves in a 3-D plane. Hence, using the largest tumour diameter will not reflect total cancer volume. We aim to evaluate the use of tongue cancer tumour volume (Tv) as a prognostic predictor of disease recurrence and survival. METHODS: The study is a retrospective analysis of patients in Singapore General Hospital who underwent complete resection for histologically proven tongue carcinoma from 2000 to 2002. The Tv was measured on staging T(2)-weighted magnetic resonance imaging datasets by semiautomated methods. RESULTS: Seventeen patients with a median follow-up duration of 57.9 months were studied. A wide range of volumes was noted in each T stage. The median time to relapse was 8.6 months for those with Tv > or = 13 cc but was not achieved for those with Tv < 13 cc. The hazard ratio comparing Tv > or = 13 cc versus <13 cc is 9.02 (95% confidence interval (CI) 1.70-47.94, P = 0.014). Of the seven deaths reported, five patients had Tv > or = 13 cc. The median overall survival was 15.8 months for those with Tv > or = 13 cc but was not achieved for those with Tv < 13 cc. The hazards of death for Tv > or = 13 cc was 3.91 times that of Tv < 13 cc (95% CI 0.86-17.86, P = 0.078). CONCLUSION: Tongue cancer Tv measurement allows a more refined and accurate assessment of tumour status. This can be a possible prognostic indicator and be used in a novel staging method for the future.

Extraction of metastatic lymph nodes from MR images using two deformable model-based approaches.

We presented and evaluated two deformable model-based approaches, region plus contour deformation (RPCD), and level sets to extract metastatic cervical nodal lesions from pretreatment T2-weighted magnetic resonance images. The RPCD method first uses a region deformation to achieve a rough boundary of the target node from a manually drawn initial contour, based on signal statistics. After that, an active contour deformation is employed to drive the rough boundary to the real node-normal tissue interface. Differently, the level sets move a manually drawn initial contour toward the desired nodal boundary under the control of the evolvement speed function, which is influenced by image gradient force. The two methods were tested by extracting 33 metastatic cervical nodes from 18 nasopharyngeal carcinoma patients. Experiments on a basis of pixel matching to reference standard showed that RPCD and level sets achieved averaged percentage matching at 82-84% and 87-88%, respectively. In addition, both methods had significantly lower interoperator variances than the manual tracing method. It was suggested these two methods could be useful tools for the evaluation of metastatic nodal volume as an indicator of classification and treatment response, or be alternatives for the delineation of metastatic nodal lesions in radiation treatment planning.