Richard P. Golding

Modern imaging techniques and ultrasound-guided aspiration cytology for the assessment of neck node metastases: a prospective comparative study

SummaryAlthough palpation has proved to be an unreliable staging procedure, the indications for and the implications of more reliable radiologic staging methods for the neck in patients with a primary squamous cell carcinoma of the head and neck remain controversial. Only a very accurate imaging technique can replace neck dissection in clinical NO disease. This study compares the value of palpation with computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound (US) with or without guided aspiration cytology for neck node staging. One hundred and thirty-two patients with squamous cell carcinoma of the head and neck were examined radiologically before undergoing a total of 180 neck dissections as part of their treatment. CT, US and MRI proved to be significantly more accurate than palpation for cervical lymph node staging. The accuracy of US-guided aspiration cytology was significantly better than of any other technique used in this study. Modern imaging techniques are essential for appropriate assessment of neck node metastases. In view of advances in the accuracy of contemporary imaging, the need for elective treatment of the neck requires reappraisal.

Prognostic Relevance of Response Evaluation Using [18F]-2-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography in Patients With Locally Advanced Non–Small-Cell Lung Cancer

PURPOSE The objective of this study was to determine the accuracy of (early) response measurements using [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography (18FDG PET) with respect to survival of patients with stage IIIA-N2 non-small-cell lung cancer (NSCLC) undergoing induction chemotherapy (IC), with a comparative analysis of PET methods. PATIENTS AND METHODS In a prospective multicenter study, PET was performed in patients before IC and after one and three cycles. Computed tomography (CT) was performed before and after IC. Glucose consumption (metabolic rate of glucose [MRglu]) was measured using Patlak graphical analysis and correlated with simplified methods. Mediastinal lymph node (MLN) status was assessed visually. Cox proportional hazards analysis was used to determine the prognostic relevance of CT and PET measures of response with respect to survival. RESULTS Complete PET data sets were available in 47 patients. Median survival was 21 months. MLN status after IC by PET predicted survival (hazard ratio [HR], 2.33; 95% CI, 1.04 to 5.22; P = .04) in contrast with CT (HR, 1.87; 95% CI, 0.81 to 4.30; P = .14). Residual MRglu after IC proved to be the best prognostic factor (HR, 1.95; 95% CI, 1.28 to 2.97; P = .002). Multivariate stepwise analysis showed that PET identified prognostically different strata in patients considered responsive according to CT. Residual MRglu after one cycle selected patients with different outcomes (HR, 2.04; 95% CI, 1.18 to 3.52; P = .01). Simplified quantitative 18FDG PET methods were correlated with Patlak graphical analysis during and after therapy (r > or = 0.90). CONCLUSION 18FDG PET has additional value over CT in monitoring response to IC in patients with stage IIIA-N2 NSCLC, and it seems feasible to predict survival early during IC. Simple semiquantitative and complex PET methods perform equally well.

Radiographically occult lung cancer treated with fibreoptic bronchoscopic electrocautery: a pilot study of a simple and inexpensive technique

The curative potential of bronchoscopic intervention, e.g. photodynamic therapy (PDT) and brachytherapy, for resectable radiographically occult lung cancer has been reported previously. Bronchoscopic electrocautery is currently feasible using an insulated flexible bronchoscope to coagulate and vaporize tumour tissue. Since the lesions are usually small, noninvasive bronchoscopic electrocautery may be able to eradicate radiographically occult lung cancer completely. In a prospective study, 13 patients with 15 radiographically occult lung cancer lesions were treated with bronchoscopic electrocautery. The duration of follow-up was > or = 16 months. The median age of the patients was 69 yrs (range 48-79 yrs). Fibreoptic bronchoscopy under local anaesthesia was used to coagulate the occult lung cancer. Approximately 30 W of energy was applied until visible necrosis of the tumour area became apparent. There were no immediate complications. In 10 patients with 12 lesions, a complete response (CR) was obtained (CR rate 80%; 95% confidence interval (95% CI) 52-96%). Median duration of follow-up was 21 months (range 16-43 months). Bronchoscopic electrocautery did not obtain a CR in the remaining three patients, but PDT also failed to achieve CR. Two patients underwent radical resection, and the tumours were histologically confirmed to be more invasive. One patient received external radiotherapy. Three patients with a CR died during follow-up, two as a result of myocardial infarction and apoplexy, and one because of metastasis from his previously resected T3N1 primary large cell cancer. Current data show bronchoscopic electrocautery to be equally effective and potentially as curative as photodynamic therapy for treating patients with radiographically occult lung cancer. Obvious advantages are that it is an inexpensive and simple procedure, which does not cause photosensitivity.

Prospective study on the dose relationship of mitomycin C–induced interstitial pneumonitis

Lung damage after mitomycin C (MMC) was first reported in 1978. Although this side effect has been frequently reported since then, there are no data on dose dependency nor on incidence. Therefore, the authors initiated a prospective study to obtain more data on this subject. Forty‐four patients treated with MMC entered the study; 37 were evaluable. All patients were subjected to repeated physical examinations, chest x‐rays, chest computed tomography (CT) scan and pulmonary function tests. The results were evaluated per cumulative dose level. None of the patients had clinical pulmonary toxicity develop; one patient had pulmonary changes on CT scan, the significance of which remained unclarified. The world literature on this subject was also reviewed. Based on the combined data of the present study as well as the literature review, the authors concluded that MMC‐related lung toxicity is a dose‐dependent side effect, occurring at cumulative dose levels of 20 mg/m2 or more. The incidence is likely to be less than 10%.

A phase I–II study of gemcitabine and paclitaxel in advanced non-small-cell lung cancer patients

Thirty patients with chemotherapy-naïve advanced non-small-cell lung cancer (NSCLC) were given escalating doses of paclitaxel (150, 175, 200 mg/m2) on day 1 in three consecutive cycles, together with a fixed dose of gemcitabine 1000 mg/m2 on days 1 and 8; cycles were repeated every three weeks. The dose escalation of paclitaxel was feasible in the majority of patients. Subsequently, 30 other NSCLC patients received a dose of 200 mg/m2 paclitaxel with gemcitabine 1000 mg/m2 in a phase II study. The major side effect was mild myelosuppression. A response rate of 24% was achieved in 49 fully evaluable patients. This regimen proved to be safe and easy to administer on an out-patient setting, and constitutes now one of the arms of the current EORTC randomized study for advanced NSCLC.

Bone marrow magnetic resonance studies in childhood leukemia. Evaluation of osteonecrosis

In 25 patients under treatment or during follow‐up for acute lymphoblastic leukemia magnetic resonance imaging (MRI) of both knees was compared to history and physical examination to detect osteonecrosis. Results of MRI were classified as: O, normal bone marrow (BM); 1, diffuse decrease in signal intensity; 2, circumscript lesions. Patients clinically suspected of osteonecrosis had a statistically significant increased incidence of Type 2 lesions. Three patients with a BM relapse also showed Type 2 lesions. Circumscript lesions of the epiphyses were seen exclusively in the four patients with clinical suspicion of osteonecrosis during BM remission and this may be a MR finding strongly indicative of osteonecrosis. Patients with Type 2 lesions during BM remission had received systemic chemotherapy for a statistically significant longer period than the other patients. Using MRI findings we suspect that at least four patients suffered osteonecrosis due to chemotherapy. MRI is a promising means of detecting this disorder.

Early Detection of Local RFA Site Recurrence Using Total Liver Volume Perfusion CT: Initial Experience

RATIONALE AND OBJECTIVES The aim of this study was to prospectively evaluate the feasibility of a novel total liver volume perfusion computed tomographic technique in demonstrating treatment-site recurrence of liver metastases after radiofrequency ablation (RFA). MATERIALS AND METHODS Eleven patients considered to be at increased risk for local RFA-site tumor recurrence underwent both positron emission tomography (PET) and perfusion computed tomography (CTP): a 12-phase scan of the entire liver acquired before and 11 times after contrast injection. After coregistration, blood flow maps were created using the maximum slope method. RESULTS In all cases, the CTP-derived blood flow maps fully paralleled the PET images in showing either the absence (nine of 13 lesions) or presence (four of 13 lesions) of local RFA-site recurrence. Marginal lesions with high hepatic arterial perfusion (>50 mL/min/100 g) and low portal venous perfusion (<10 mL/min/100 g) represented recurring vital tumor tissue (P < .05). CONCLUSION Total liver volume CTP seems feasible for the detection and localization of treatment-site recurrence after RFA.

Early response monitoring in malignant lymphoma using fluorine-18 fluorodeoxyglucose single-photon emission tomography.

Metabolic response monitoring early during chemotherapy may have a major impact on clinical management of patients with malignant lymphoma. In two patients with non-Hodgkins lymphoma fluorine-18 fluorodeoxyglucose (IgFDG) single-photon emission tomography (SPET) studies were performed during the first two chemotherapeutic cycles. Persisting uptake predicted treatment failure whereas a sharp reduction of 18FDG uptake was demonstrated in the case of a responsive tumour. Qualitative analysis of conventional 18FDG imaging may thus serve to identify patients with a non-responding tumour. The potential of this technique in the determination of the initial response remains to be established. Imaging with 18FDG and SPET appears promising as a more easily available methodology than 18FDG positron emission tomography.

Severe acute lung injury induced by gemcitabine.

Gemcitabine is a nucleoside analog that is active in the treatment of various solid tumors. In general it is well tolerated and has few side effects. Pulmonary toxicity reported with gemcitabine use is usually mild and self-limiting. We present a case of severe pulmonary dysfunction after intravenous administration of a single dose of gemcitabine in a 58-year-old female patient with metastatic carcinoma of the pancreas. She developed tachypnea, marked hypoxemia, and an interstitial infiltrate on chest radiograph consistent with pulmonary edema, 4 days after receiving this drug. Diuretics and corticosteroids were beneficial in treating the acute respiratory failure. Pulmonary damage was completely resolved by means of clinical and radiological assessment. Because of the severity of this side effect, no further treatment with gemcitabine was given. Eventually, the patient died because of obstruction of the bowel due to progression of tumor growth. Publications concerning severe pulmonary toxicity due to gemcitabine are sparse. Pathophysiology and treatment are considered and a review of the literature is presented.

Phase II trial of combined radiotherapy and daily low-dose cisplatin for inoperable, locally advanced non-small cell lung cancer (NSCLC)

With the use of cis-diamminedichloroplatinum(II), cisplatin, to enhance the effect of radiation a combined modality approach was designed to treat patients with inoperable, locally advanced NSCLC. The regimen consisted of radiation doses of 300 cGy for 4 days every week for 4 weeks with a 2 week split in between. Each radiation dose was followed by an i.v. injection of cisplatin 6 mg/m2 within 30 min. Hydration consisted on an oral fluid intake of 2 L only, enabling the patient to receive the treatment on an outpatient basis. Of 40 patients entered into the study, 37 were evaluable for toxicity and 33 for response. Overall response rate was 65% and complete response rate 22%. Median duration of local control was 7 months. The majority of all patients (76%) eventually progressed at the primary tumor site, while in 16 patients relapse occurred in distant sites first. Median duration of overall survival was 10.5 months, whereas that of complete responders was 29.5 months. Generally, acute side effects were transient and did not require discontinuation of treatment. One patient presented with thrombocytopenia 4 weeks after treatment had been finished. His death of cerebral bleeding was likely to be related with his therapy-resistant malignancy. Of late side effects three patients showed disabling symptoms consisting of uncontrollable pulmonary infections in the presence of tumor in two patients, one patient had radiation myelopathy and another experienced vertebral collapse with distal paresis. The combination of radiation and daily low-dose cisplatin is a tolerable treatment modality with most benefit for patients reaching a complete remission. Intensification of the regimen is being planned in those patients with inoperable, locally advanced squamous cell lung cancer to reach a complete remission.