A.D. King

Phase II study of neoadjuvant carboplatin and paclitaxel followed by radiotherapy and concurrent cisplatin in patients with locoregionally advanced nasopharyngeal carcinoma: Therapeutic monitoring with plasma Epstein-Barr virus DNA

PURPOSE To assess the efficacy of neoadjuvant paclitaxel and carboplatin (TC) followed by concurrent cisplatin and radiotherapy (RT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and to monitor treatment response with plasma Epstein-Barr virus (EBV) DNA. PATIENTS AND METHODS Thirty-one patients with International Union Against Cancer stages III and IV undifferentiated NPC had two cycles of paclitaxel (70 mg/m2 on days 1, 8, and 15) and carboplatin (area under the curve 6 mg/mL/min on day 1) on a 3-weekly cycle, followed by 6 to 8 weeks of cisplatin (40 mg/m2 weekly) and RT at 66 Gy in 2-Gy fractions. Plasma EBV DNA was measured serially using the real-time quantitative polymerase chain reaction method. Results All patients completed planned treatment. Response to neoadjuvant TC was as follows: 12 patients (39%) achieved partial response (PR) and 18 achieved (58%) complete response (CR) in regional nodes; five patients (16%) achieved PR and no patients achieved CR in nasopharynx. At 6 weeks after RT, one patient (3%) achieved PR and 30 patients (97%) achieved CR in regional nodes, and 31 patients (100%) achieved CR in nasopharynx; 29 patients (93%) had EBV DNA level of less than 500 copies/mL. Neoadjuvant TC was well tolerated, and the most common acute toxicity of cisplatin plus RT was grade 3 mucositis (55%). At median follow-up of 33.7 months (range, 7 to 39.3 months), six distant and three locoregional failures occurred. Plasma EBV DNA level increased significantly in eight of nine patients who experienced treatment failure but did not increase in those who did not. The 2-year overall and progression-free survival rates were 91.8% and 78.5%, respectively. CONCLUSION This strategy was feasible and resulted in excellent local tumor control. Serial plasma EBV DNA provides a noninvasive method of monitoring response in NPC.

Lymph node hilus: gray scale and power Doppler sonography of cervical nodes.

To investigate the difference in the nodal hilus evaluated by gray scale and power Doppler sonography.

Liver resection after irinotecan, 5-fluorouracil, and folinic acid for patients with unresectable colorectal liver metastases : a multicenter phase II study by the Cancer Therapeutic Research Group

The main objectives of this study were to assess the use of irinotecan, 5-fluorouracil (5-FU), and leucovorin (FA) as neoadjuvant chemotherapy for patients with unresectable colorectal liver metastases and to determine the response rate and proportion of patients that could be downstaged to resectable tumors. Forty patients were treated with irinotecan (180 mg/m2 over 30 min) on d 1, FA (200 mg/m2 over 30 min) followed by 5-FU (400 mg/m2 bolus and continuous infusion of 600 mg/m2 over 22 h) on d 1 and 2 every 2 wk. The overall response rate was 55% (95% CI: 39.5–70.4%). The progression-free survival was 12.1 mo (95% CI: 11.4–14.8 mo). The median overall survival was 20 mo (95% CI: 17.7–26.6 mo). Four patients (10%) have undergone liver resection after a median of eight cycles. Those patients remained alive with a median follow up period of 33 mo. The principal grade 3–4 toxicity was neutropenia in 20 patients (50%). We conclude that the regimen of irinotecan/5-FU/FA was highly active in patients with colorectal cancer and liver metastases with limited toxicity. In a subgroup of patients with initial inoperable liver metastases, this regimen was able to downstage the disease to an operable stage.

Hemorrhagic complications in a phase II study of sunitinib in patients of nasopharyngeal carcinoma who has previously received high-dose radiation

BACKGROUND We aimed to evaluate the safety and efficacy of single-agent sunitinib in nasopharyngeal carcinoma (NPC). METHODS Eligible patients had progressive disease after prior platinum-based chemotherapy. Sunitinib was given as continuous once-daily dosing of 37.5 mg in 4-week cycles until progression. RESULTS Thirteen patients were enrolled. Recruitment was stopped after two patients died of hemorrhagic events. All patients had previously received curative radiotherapy (RT) to nasopharynx/neck (including nine patients who had chemoradiotherapy). Patients received a median of three cycles of sunitinib. One patient was still on sunitinib with stable disease after 24 cycles. Hemorrhagic events occurred in nine patients (64%), including epistaxis in six, hemoptyses in three and hematemesis in two patients. Prior RT to thorax was significantly associated with hemoptyses (P = 0.03). Two patients with local tumor invasion into the carotid sheath developed fatal epistaxis/hematemesis within the first cycle of sunitinib, likely due to internal carotid blowout after tumor shrinkage. CONCLUSIONS Sunitinib demonstrated modest clinical activity in heavily pretreated NPC patients. However, the high incidence of hemorrhage from the upper aerodigestive tract in NPC patients who received prior high-dose RT to the region is of concern. Direct vascular invasion by tumors appeared to increase the risk of serious bleeding.

Analysis of Plasma Epstein–Barr Virus DNA to Screen for Nasopharyngeal Cancer

BACKGROUND Circulating cell‐free Epstein–Barr virus (EBV) DNA is a biomarker for nasopharyngeal carcinoma. We conducted a prospective study to investigate whether EBV DNA in plasma samples would be useful to screen for early nasopharyngeal carcinoma in asymptomatic persons. METHODS We analyzed EBV DNA in plasma specimens to screen participants who did not have symptoms of nasopharyngeal carcinoma. Participants with initially positive results were retested approximately 4 weeks later, and those with persistently positive EBV DNA in plasma underwent nasal endoscopic examination and magnetic resonance imaging (MRI). RESULTS A total of 20,174 participants underwent screening. EBV DNA was detectable in plasma samples obtained from 1112 participants (5.5%), and 309 (1.5% of all patients and 27.8% of those who initially tested positive) had persistently positive results on the repeated sample. Among these 309 participants, 300 underwent endoscopic examination, and 275 underwent both endoscopic examination and MRI; of these participants, 34 had nasopharyngeal carcinoma. A significantly higher proportion of participants with nasopharyngeal carcinoma that was identified by screening had stage I or II disease than in a historical cohort (71% vs. 20%, P<0.001 by the chi‐square test) and had superior 3‐year progression‐free survival (97% vs. 70%; hazard ratio, 0.10; 95% confidence interval, 0.05 to 0.18). Nine participants declined to undergo further testing, and 1 of them presented with advanced nasopharyngeal carcinoma 32 months after enrollment. Nasopharyngeal carcinoma developed in only 1 participant with negative EBV DNA in plasma samples within 1 year after testing. The sensitivity and specificity of EBV DNA in plasma samples in screening for nasopharyngeal carcinoma were 97.1% and 98.6%, respectively. CONCLUSIONS Analysis of EBV DNA in plasma samples was useful in screening for early asymptomatic nasopharyngeal carcinoma. Nasopharyngeal carcinoma was detected significantly earlier and outcomes were better in participants who were identified by screening than in those in a historical cohort. (Funded by the Kadoorie Charitable Foundation and the Research Grants Council of the Hong Kong government; ClinicalTrials.gov number, NCT02063399.)

The role of ultrasound in the diagnosis of a large, rapidly growing, thyroid mass.

The value of ultrasound in the diagnosis of a large rapidly growing thyroid mass was assessed in a study of 42 patients with a large (> 3 cm) rapidly growing (< two months) solitary mass. Haemorrhage into a thyroid nodule was present in 31 patients and thyroid malignancy in 11. Ultrasound of haemorrhage into a thyroid nodule revealed a large cystic mass in all 31 patients containing internal debris (22), septations (three), or a combination of both (six). The malignant causes of a large rapidly growing mass were lymphoma (two), anaplastic carcinoma (four) and metastasis (five). Ultrasound of these thyroid malignancies revealed a mass with a smooth, well-defined margin and strikingly low homogeneous echogenicity in all cases. Patients with thyroid metastases had evidence of widespread metastatic disease elsewhere. Lymphoma was differentiated from anaplastic carcinoma on fine-needle aspiration cytology or surgical biopsy. Ultrasound was of value in differentiating between a benign haemorrhagic nodule and a malignant tumour. The various malignant tumours had similar appearances, however, and could not be distinguished on ultrasound.

State of the art MRI in head and neck cancer

Head and neck cancer affects more than 11,000 new patients per year in the UK1 and imaging has an important role in the diagnosis, treatment planning, and assessment, and post-treatment surveillance of these patients. The anatomical detail produced by magnetic resonance imaging (MRI) is ideally suited to staging and follow-up of primary tumours and cervical nodal metastases in the head and neck; however, anatomical images have limitations in cancer imaging and so increasingly functional-based MRI techniques, which provide molecular, metabolic, and physiological information, are being incorporated into MRI protocols. This article reviews the state of the art of these functional MRI techniques with emphasis on those that are most relevant to the current management of patients with head and neck cancer.

Palatal lymphoepitheliomas and a review of head and neck lymphoepitheliomas

AIM Lymphoepithelioma is principally a tumour of the nasopharynx with only sporadic cases arising elsewhere in the head and neck. We describe the clinical and imaging features of a group of rare lymphoepitheliomas related to the palate. PATIENTS AND METHODS Four patients with lymphoepithelioma of the palate are described. In each case we retrospectively reviewed the clinical records, laboratory results, and imaging which consisted of computed tomography (CT) and ultrasound in all four cases and magnetic resonance imaging (MRI) in two patients. RESULTS All four patients were ethnic Chinese (non-smokers, non-drinkers). All cases were Epstein-Barr virus (EBV) related. Tumour was related to the palate in two cases and extended into the nasal cavity in one patient. The fourth patient had a tumour in the floor of the nasal cavity with invasion of the palate on biopsy but not imaging. Cervical lymphadenopathy was seen in two cases, and the nasopharynx was normal in all the four patients. CONCLUSION Lymphoepitheliomas occur in the region of the palate, where they are also EBV related in southern Chinese. Compared with the keratinizing squamous cell carcinomas, patients with lymphoepitheliomas have a better prognosis and these tumours are not tobacco or alcohol related. They should not be misdiagnosed as metastatic nasopharyngeal carcinoma (NPC), particularly since the nasopharynx is invariably normal on imaging and adequate nasopharyngeal biopsy is negative for malignancy.

Prospective evaluation of plasma Epstein–Barr virus DNA clearance and fluorodeoxyglucose positron emission scan in assessing early response to chemotherapy in patients with advanced or recurrent nasopharyngeal carcinoma

BackgroundPlasma Epstein–Barr virus (pEBV) DNA and fluorodeoxyglucose positron emission (PET) reflect tumour burden in advanced NPC. This study hypothesised that a dual endpoint based on assessing pEBV DNA clearance and PET response could predict early drug response.MethodsEligible patients underwent a computed tomography (CT) scan and dual PET-CT at baseline, a PET-CT at 4 weeks, and then a CT scan at 10 weeks after starting palliative or induction chemotherapy. Plasma EBV DNA clearance was determined.ResultsFifty-eight out of 70 enrolled patients completed all imaging and 50/58 had falling pEBV DNA level, which allowed calculation of the clearance. At a median follow-up of 29.1 months, the dual endpoint (pEBV DNA clearance ≤ 10 days and > 50% drop in sum of SUVmax of target lesions) was an independent indicator of overall survival (hazard ratio (HR) = 0.135, 95% CI = 0.039 to 0.466, p = 0.0015) and progression-free survival (HR = 0.136, 95% CI = 0.048 to 0.385, p = 0002). This dual endpoint could predict subsequent response by Response Evaluation Criteria In Solid Tumours (RECIST) criteria at 10 weeks after chemotherapy.ConclusionsEarly PET-CT response and pEBV DNA clearance could predict survival and subsequent response. This dual endpoint is an innovative tool for assessing early drug response.

Identifying an early indicator of drug efficacy in patients with metastatic colorectal cancer—a prospective evaluation of circulating tumor cells, 18F-fluorodeoxyglucose positron-emission tomography and the RECIST criteria

Background This study investigated the predictive and prognostic significance of assessing early drug response with both positron-emission computerized tomography (PET-CT) and circulating tumor cells (CTCs) in patients receiving first-line chemotherapy for metastatic colorectal cancer. Patients and methods Eligible patients had PET-CT and CTC analysis at baseline and 4-6 weeks after starting chemotherapy, and then a CT scan at 10-12 weeks to assess the Response Evaluation Criteria In Solid Tumors (RECIST) response. Early response was defined as achieving a dual-endpoint consisting of PET-CT (30% drop in the sum of maximum standard uptake values-SUVmax-of target lesions) and CTC response (CTC < 3 cells/7.5 ml blood) at 4-6 weeks after starting chemotherapy. Results About 84 patients were enrolled with a median follow-up of 32.9 months (95% confidence interval, CI, 24.5 months-not reached, NR), and 70 patients (84.3%) completed all assessments. Achieving an early response based on the dual-endpoint was independently associated with progression-free survival (hazard ratio, HR = 0.452, 95% CI 0.267-0.765). The median progression-free survival of early responders was 7.41 months (95% CI, 6.05-9.11) compared with 5.37 months (95% CI, 4.68-6.24) in non-responders (log-rank, P = 0.0167). RECIST response at 10 weeks was independently associated with overall survival (OS) (HR = 0.484, 95% CI, 0.275-0.852). Early response based on the dual-endpoint could predict the subsequent RECIST response with a sensitivity, specificity and positive predictive value of 64%, 70% and 74%, respectively. Conclusions Early response based on both PET-CT and CTC analysis has prognostic and probably predictive significance in patients undergoing first-line chemotherapy for metastatic colorectal cancer. Its utility as a new tool for assessing early drug response should be further validated.