The diagnostic dilemma of primary central nervous system melanoma

Melanomas are malignant neoplasms of melanocytes developing predominantly in the skin, but occasionally arising from eyes, mucous membranes, and the central nervous system (CNS). The CNS can be affected by a spectrum of melanocytic lesions ranging from diffuse neurocutaneous melanosis, to a focal and benign neoplasm (melanocytoma), and to an overtly malignant tumor (melanoma). Primary melanocytic lesions involving the CNS are typically concentrated in the perimedullary and high cervical region. Primary CNS melanoma cannot be reliably distinguished from metastatic melanoma on neuroimaging and histopathological characteristics alone: its diagnosis is established only after exclusion of secondary metastatic disease from a cutaneous, mucosal or retinal primary. We present two patients with primary CNS melanoma and discuss relevant issues, available treatment options, and expected outcomes. Awareness of disease spectrum and clinico-biological differences may be used to guide therapeutic decision-making for a patient with a proven or suspected primary CNS melanoma.     

Objective assessment of swallowing function after definitive concurrent (chemo)radiotherapy in patients with head and neck cancer

The aim of this study was to objectively assess swallowing function and factors impacting it after curative intent definitive (chemo)radiotherapy (CRT) for head and neck squamous cell carcinoma (HNSCC). Swallowing function was studied in a cohort of 47 patients with locoregionally advanced (T1?C4, N0?C3) HNSCC treated with definitive CRT. Objective assessment of swallowing function was done using modified barium swallow (MBS) at baseline (pre-CRT) and subsequent follow-ups. Scoring of MBS was done using penetration?Caspiration scale (PAS). Abnormal swallowing was defined in terms of incidence and severity of penetration?Caspiration, pharyngeal residue, postural change, and regurgitation. Aspiration, residual, postural change, and regurgitation were present on baseline pre-CRT assessment in 9 (19%), 11 (23%), 10 (21%), and 5 (10%) patients that increased to 11 (29%), 11 (29%), 12 (32%), and 10 (26%) patients, respectively, at 6-month post-CRT evaluation. The proportion of patients with high PAS scores (3-7) increased from 27% at baseline to 37% at 6-month post-CRT evaluation. Among patients (n?=?34) with low PAS scores (??2) at baseline, additional impairment of swallowing function was seen in 53 and 46% at 2- and 6-month assessment, respectively. Residue (44%) and aspiration (18%) domains were impaired in a higher proportion of patients after CRT. Thin and thick barium had higher aspiration and residue function impairment, respectively. Patients with pre-CRT poor subjective swallowing function (P?=?0.004), hypopharyngeal primary (P?=?0.05), and large tumor volume (P?=?0.05) had significantly worse objective swallowing function at baseline as demonstrated by pretreatment PAS scores. This study provides useful information regarding patterns of objective swallowing dysfunction in patients treated with definitive (chemo)radiotherapy. There is significant impairment of objective swallowing function in all domains following CRT, with residue and aspiration domains being affected most significantly.     

Molecular biology of medulloblastoma: bridging the gap between research and practice

Medulloblastoma, the most common primary pediatric malignant brain tumor, is a molecularly heterogeneous disease with different developmental origins, distinct phenotypes, diverse biological behavior and contrasting clinical outcomes. The current clinico-radiological risk classification fails to take account of this heterogeneity and resultant prognostic variability. It is widely accepted that dysregulation of normal developmental processes constitutes a key mechanism of tumorigenesis in at least a subset of medulloblastomas. Several attempts at biological classification have successfully identified distinct subgroups with subgroup-specific gene signatures, demographics, histologic subtypes and metastases; among these, tumors involving the wingless and sonic hedgehog signaling pathways have been the most reliably and consistently identified. However, such integrative genomic approaches have limited applicability in the clinic owing to the need for fresh frozen tissues and elaborate molecular biology tools. A novel four-antibody approach to subgroup medulloblastoma using immunohistochemistry on archival specimens as proposed by Northcott et al. appears extremely promising as it can be applied in any basic neuropathology laboratory across the globe. There is a compelling need to integrate assays of molecular biomarkers performed on archival specimens into stratification schemes for medulloblastoma alongside clinical and pathologic outcome indicators to refine risk stratification for individualizing therapy.     

Diagnostic performance of post-treatment FDG PET or FDG PET/CT imaging in head and neck cancer: a systematic review and meta-analysis

Purpose

Our objective was to conduct a systematic review and meta-analysis of studies assessing the diagnostic performance of ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG PET) with or without computed tomography (CT) in post-treatment response assessment and/or surveillance imaging of head and neck squamous cell carcinoma (HNSCC).

Methods

A systematic search of the indexed medical literature was done using appropriate keywords to identify relevant studies. Metrics of diagnostic test accuracy, viz. sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were extracted from individual studies and combined using a random effects model to yield weighted mean pooled estimates with 95% confidence intervals (95% CI). The impact of timing of post-treatment scan, study quality and advancements in PET technology was explored through meta-regression.

Results

A total of 51 studies involving 2,335 patients were included in the meta-analysis. The weighted mean (95% CI) pooled sensitivity, specificity, PPV and NPV of post-treatment FDG PET(CT) for the primary site was 79.9% (73.7?C85.2%), 87.5% (85.2?C89.5%), 58.6% (52.6?C64.5%) and 95.1% (93.5?C96.5%), respectively. Similar estimates for the neck were 72.7% (66.6?C78.2%), 87.6% (85.7?C89.3%), 52.1% (46.6?C57.6%) and 94.5% (93.1?C95.7%), respectively. Scans done ??12?weeks after completion of definitive therapy had moderately higher diagnostic accuracy on meta-regression analysis using time as a covariate.

Conclusion

The overall diagnostic performance of post-treatment FDG PET(CT) for response assessment and surveillance imaging of HNSCC is good, but its PPV is somewhat suboptimal. Its NPV remains exceptionally high and a negative post-treatment scan is highly suggestive of absence of viable disease that can guide therapeutic decision-making. Timing of post-treatment imaging has a significant, though moderate impact on diagnostic accuracy.     

Factors predicting temozolomide induced clinically significant acute hematologic toxicity in patients with high-grade gliomas: A clinical audit

Introduction

Myelo-suppression, the dose-limiting toxicity of alkylating cytotoxic agents is generally perceived to be uncommon with temozolomide (TMZ), a novel oral second generation imidazotetrazinone prodrug, with a reported incidence of 5–10% of grade 3–4 acute hematologic toxicity. We were observing a higher incidence of clinically significant myelo-toxicity with the standard schedule of TMZ, particularly in females, prompting us to do a clinical audit in our patient population.

Methods

One hundred two adults (>18 years of age) treated with TMZ either for newly diagnosed or recurrent/progressive high-grade glioma constituted the study cohort. Clinically significant acute hematologic toxicity was defined as any one or more of the following: any grade 3–4 hematologic toxicity; omission of daily TMZ dose for ≥3 consecutive days during concurrent phase; deferral of subsequently due TMZ cycle by ≥7 days during adjuvant phase; dose reduction or permanent discontinuation of TMZ; use of growth factors, platelets or packed-cell transfusions during the course of TMZ. Uni-variate and multi-variate analysis was performed to correlate incidence of acute hematologic toxicity with baseline patient, disease, and treatment characteristics.

Results

The incidence of clinically significant neutropenia and thrombocytopenia was 7% and 12% respectively. Seven (7%) patients needed packed-cells, growth factors, and/or platelet transfusions. Grade 3–4 lymphopenia though common (32%) was self-limiting and largely asymptomatic. Two (2%) patients, both women succumbed to community acquired pneumonia during adjuvant TMZ. Multi-variate logistic regression analysis identified female gender, grade IV histology, baseline total leukocyte count <7700/mm³ and baseline serum creatinine ≥1 mg/dl as factors associated with significantly increased risk of clinically significant acute hematologic toxicity.

Conclusion

The incidence of TMZ induced clinically significant neutropenia and thrombocytopenia was low in our patient population. Severe lymphopenia though high was largely asymptomatic and self-limiting. Gender, grade, leukocyte count, and serum creatinine were significant independent predictors of severe acute myelo-toxicity.     

Isolated prostatic metastasis from primary sigmoid colon carcinoma.

Metastasis to the prostate is extremely uncommon. We report a 38-year-old man with sigmoid colon carcinoma, treated with surgery and adjuvant chemotherapy, who developed isolated metastasis to the prostate four years after initial treatment. He was treated with chemoradiation and remains disease-free three years after detection of metastasis.