Primary tumor sidedness has an impact on prognosis and treatment outcome in metastatic colorectal cancer: results from two randomized first-line panitumumab studies.

BACKGROUND: Previous studies have reported the prognostic impact of primary tumor sidedness in metastatic colorectal cancer (mCRC) and its influence on cetuximab efficacy. The present retrospective analysis of two panitumumab trials investigated a possible association between tumor sidedness and treatment efficacy in first-line mCRC patients with RAS wild-type (WT) primary tumors. MATERIALS AND METHODS: Data from two randomized first-line panitumumab trials were analyzed for treatment outcomes by primary tumor sidedness for RAS WT patients. PRIME (phase 3; NCT00364013) compared panitumumab plus FOLFOX versus FOLFOX alone; PEAK (phase 2; NCT00819780) compared panitumumab plus FOLFOX versus bevacizumab plus FOLFOX. Primary tumors located in the cecum to transverse colon were coded as right-sided, while tumors located from the splenic flexure to rectum were considered left-sided. RESULTS: Tumor sidedness ascertainment (RAS WT population) was 83% (n = 559/675); 78% of patients (n = 435) had left-sided and 22% (n = 124) had right-sided tumors. Patients with right-sided tumors did worse for all efficacy parameters compared with patients with left-sided disease in the RAS WT population and also in the RAS/BRAF WT subgroup. In patients with left-sided tumors, panitumumab provided better outcomes than the comparator treatment, including on median overall survival (PRIME: 30.3 versus 23.6 months, adjusted hazard ratio = 0.73, P = 0.0112; PEAK: 43.4 versus 32.0 months, adjusted hazard ratio = 0.77, P = 0.3125). CONCLUSION: The results of these retrospective analyses confirm that in RAS WT patients, right-sided primary tumors are associated with worse prognosis than left-sided tumors, regardless of first-line treatment received. RAS WT patients with left-sided tumors derive greater benefit from panitumumab-containing treatment than chemotherapy alone or combined with bevacizumab, including an overall survival advantage (treatment difference: PRIME 6.7 months; PEAK 11.4 months). No final conclusions regarding optimal treatment could be drawn for RAS WT patients with right-sided mCRC due to the relatively low number of paxtients. Further research in this field is warranted. TRIAL REGISTRATION (CLINICALTRIALS.GOV): PRIME (NCT00364013), PEAK (NCT00819780).

PET/CT in the staging of patients with a pelvic mass suspicious for ovarian cancer.

OBJECTIVE: To prospectively assess the value of PET/CT for staging, diagnosis and operability of ovarian cancer, with special attention to the peritoneal spread. METHODS: From June 2009 to March 2011, 69 patients with suspicion of having an ovarian cancer underwent an (18)F-FDG PET/CT. To identify the diagnostic value of PET/CT, the results were compared with the findings at diagnostic laparoscopy and/or debulking surgery. RESULTS: There were 56 patients with malignant tumors and 13 with benign tumors. We observed a sensitivity and specificity of 93% and 77%, respectively for malignant tumors with PET/CT. CT alone had a sensitivity and specificity of 96% and 38%, respectively. The overall FIGO classification evaluation for PET/CT and CT were the same. For the evaluation of metastases, the sensitivity of PET/CT was worse, while the specificity was better than CT. Retroperitoneal lymph node metastases were diagnosed better with PET/CT, while there was no difference for peritoneal spread and for the intestines. PET/CT detected another unknown primary tumor in 3 (4.3%) cases. CONCLUSION: PET/CT is better than CT in detecting retroperitoneal lymph node metastases, but not for peritoneal metastases.

Polypoid endometriosis of the bladder during pregnancy mimicking urachal carcinoma.

We report a case of polypoid bladder endometriosis in pregnancy. Diagnostic workup showed a vesicouterine well-vascularized polypoid mass, suspicious for malignancy. During pregnancy, the mass was surgically resected with safe oncological margins. Pathological examination of the resected specimen revealed pseudotumoral polypoid endometriosis of the bladder. We illustrate diagnostic pitfalls in the differentiation between bladder endometriosis during pregnancy and malignancy. As a result of pregnancy-related decidualization of vesical endometriosis, differentiation between this rare occurrence and malignant transformation is challenging.

GSDME: A Potential Ally in Cancer Detection and Treatment.

Gasdermin E (GSDME) is an executioner of caspase-3 mediated regulated pyroptosis, and as such plays an important role in several cancers. Recent findings highlighted the potential of GSDME as a biomarker that can be implemented in cancer diagnosis, monitoring, and therapy.

Hotspot DAXX, PTCH2 and CYFIP2 mutations in pancreatic neuroendocrine neoplasms.

Mutations in DAXX/ATRX, MEN1 and genes involved in the phosphoinositide-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway have been implicated in pancreatic neuroendocrine neoplasms (pNENs). However, mainly mutations present in the majority of tumor cells have been identified, while proliferation-driving mutations could be present only in small fractions of the tumor. This study aims to identify high- and low-abundance mutations in pNENs using ultra-deep targeted resequencing. Formalin-fixed paraffin-embedded matched tumor-normal tissue of 38 well-differentiated pNENs was sequenced using a HaloPlex targeted resequencing panel. Novel amplicon-based algorithms were used to identify both single nucleotide variants (SNVs) and insertion-deletions (indels) present in >10% of reads (high abundance) and in <10% of reads (low abundance). Found variants were validated by Sanger sequencing. Sequencing resulted in 416,711,794 reads with an average target base coverage of 2663 ± 1476. Across all samples, 32 high-abundance somatic, 3 germline and 30 low-abundance mutations were withheld after filtering and validation. Overall, 92% of high-abundance and 84% of low-abundance mutations were predicted to be protein damaging. Frequently, mutated genes were MEN1, DAXX, ATRX, TSC2, PI3K/Akt/mTOR and MAPK-ERK pathway-related genes. Additionally, recurrent alterations on the same genomic position, so-called hotspot mutations, were found in DAXX, PTCH2 and CYFIP2. This first ultra-deep sequencing study highlighted genetic intra-tumor heterogeneity in pNEN, by the presence of low-abundance mutations. The importance of the ATRX/DAXX pathway was confirmed by the first-ever pNEN-specific protein-damaging hotspot mutation in DAXX. In this study, both novel genes, including the pro-apoptotic CYFIP2 gene and hedgehog signaling PTCH2, and novel pathways, such as the MAPK-ERK pathway, were implicated in pNEN.

The relation of CT-determined tumor parameters and local and regional outcome of tonsillar cancer after definitive radiation treatment.

PURPOSE: To investigate the value of CT-derived tumor parameters as predictor of local and regional outcome of tonsillar squamous cell carcinoma treated by definitive radiation therapy. METHODS AND MATERIALS: The pretreatment CT studies of 112 patients with tonsillar squamous cell carcinoma were reviewed. After redigitizing the films, primary and nodal tumor volume was calculated with the summation-of-areas technique. The nodal CT aspect was graded using a 3-point scale (homogenous, inhomogeneous, and necrotic). Mean follow-up time was 33 months. Actuarial statistical analysis of local and regional outcome was done for each of the covariates; multivariate analysis was performed using Cox's proportional hazards model. RESULTS: In the actuarial analysis, CT-determined primary tumor volume was significantly correlated with local recurrence rate (p < 0.05) when all patients were considered, but primary tumor volume did not predict local control within the T2, T3, and T4 category. CT-determined nodal volume was significantly related to regional outcome (p < 0.01), but nodal density was not. Total tumor volume was not significantly related to locoregional outcome (p = 0.1). In the multivariate analysis, the T and N categories were the independent predictors of local and regional outcomes, respectively. CONCLUSION: Compared to other head-and-neck sites, primary and nodal tumor volume have only marginal predictive value regarding local and regional outcome after radiation therapy in tonsillar cancer.

Dysplasia epiphysealis hemimelica (Trevor's disease).

The authors report a case of dysplasia epiphysealis hemimelica. This is a benign osteochondromatous epiphyseal overgrowth affecting most commonly the inferior limbs. The cartilage cap of the lesion can be demonstrated very accurately by MRI (gradient echo sequence). Early diagnosis and treatment is vital in preventing articular malformation and malfunction.

Acute abdominal pain due to biliary cystadenoma.

We present a case of a biliary cystadenoma, a rare benign cystic tumor arising in most cases of the intrahepatic bile ducts. A 30-year old woman presented with abdominal pain in the right upper quadrant for about 10 days with increasing severity. Radiological evaluation by means of abdominal ultrasound and CT-scan revealed a multilocular cystic lesion in the right liver lobe, not present on abdominal ultrasound performed 10 years before. The diagnosis of a biliary cystadenoma was proposed and complete surgical resection of the mass was performed.

Ovarian torsion in a premenarcheal girl: MRI findings.

Adnexal torsion is an uncommon cause of severe lower abdominal pain in women and is often difficult to distinguish from other acute abdominal conditions. However, adnexal torsion should be considered in premenarcheal girls admitted with acute abdominal pain and evidence of an ovarian mass. Accurate and early radiological diagnosis is mandatory immediately after onset of clinical symptoms in order to preserve the viability of the ovary. Ultrasound (US) is usually the first line examination performed in an emergency setting, but computed tomography (CT) and magnetic resonance imaging (MRI) can be useful in case of ambiguous US findings, especially in patients with sub-acute symptoms and a suspected adnexal mass. This case report describes the additional value of MRI in a premenarcheal girl with sub-acute right fossa pain.

Computed tomography and magnetic resonance imaging of laryngeal tumours.

The possibilities of CT and MR imaging in laryngeal tumours, focused on squamous cell carcinoma, are reviewed. As in other areas of the head and neck, the primary roll of laryngeal imaging studies is to define the extent of disease. Neither CT nor MRI show mucosal detail, but clarify the submucosal extent of disease. Both imaging modalities yield comparable results; in selected cases, they may be considered to be complementary to each other.

Laryngeal squamous cell carcinoma presenting as a prelaryngeal neck abscess: report of two cases.

Head and neck tumours presenting as a neck abscess are extremely rare. Two patients with laryngeal squamous cell carcinoma, presenting with a prelaryngeal abscess, are described. Although clinically and on the CT studies these cases were suspect for underlying malignancy, the initial biopsies were negative for cancer. Because of persistent suspicion, repeat biopsies finally confirmed the presence of a squamous cell carcinoma. Pathological examination after total laryngectomy showed cancer localised in one of the true vocal cords, invading the anterior commissure and thyroid cartilage. However, the prelaryngeal soft tissues were free of tumour, showing only inflammatory changes and collections of pus. These cases emphasize the importance of repeat targeted biopsies and follow-up CT-studies in patients with a prelaryngeal abscess of obscure aetiology, in order to exclude or confirm a possible underlying malignancy.

Juvenile fibrosarcoma of the temporal bone.

A case of juvenile fibrosarcoma arising from the head and neck region is described. This type of tumour should be considered as a separate entity different from the fibrosarcoma in adults because of the different clinical behaviour. The symptomatology, the radiographic features and the literature data are reviewed.