John Plukker

Sentinel node biopsy for melanoma in the head and neck region

Lymphatic drainage in the head and neck region is known to be particularly complex. This study explores the value of sentinel node biopsy for melanoma in the head and neck region.

Imatinib induces hypothyroidism in patients receiving levothyroxine

Interactions of imatinib with other drugs have been scarcely reported. We report a previously unknown effect of imatinib on levothyroxine therapy. Eleven patients (1 with gastrointestinal stromal tumor and 10 with medullary thyroid carcinoma) received imatinib. Eight had undergone thyroidectomy and used levothyroxine, and 3 had the thyroid in situ. Thyroid function was measured before, during, and within 2 weeks after any change in either imatinib or levothyroxine dosage. We observed symptoms of hypothyroidism in all patients who had undergone thyroidectomy, whereas patients with the thyroid in situ remained clinically and biochemically euthyroid. On average, thyrotropin (INN, thyrotrophin) levels increased to 384% ± 228% of the upper limit in patients after thyroidectomy, whereas free thyroxine (fT4) and free tri‐iodothyronine (fT3) values remained within the reference range (59% ± 17% of the upper limit for fT4 and 63% ± 4% of the upper limit for fT3). Clinicians should be aware that hypothyroid subjects receiving imatinib have a high likelihood for increased levothyroxine replacement and should be closely monitored for elevations in thyrotropin indicating worsening hypothyroidism.

Determination of TP53 Mutation Is More Relevant Than Microsatellite Instability Status for the Prediction of Disease-Free Survival in Adjuvant-Treated Stage III Colon Cancer Patients

PURPOSE Microsatellite instability (MSI), TP53 mutation, and KRAS mutation status have been reported as prognostic factors in colon cancer. Most studies, however, have included heterogeneous groups of patients with respect to cancer stage. We determined the prognostic relevance of high-frequency MSI (MSI-H), TP53 mutations, and KRAS mutations in a well-defined group of patients with stage III colon cancer (N = 391), randomly assigned for adjuvant treatment with fluorouracil-based chemotherapy. METHODS Three hundred ninety-one tumor specimens were available. MSI was determined in 273 specimens, and mutation analyses of TP53 and KRAS were performed in 220 and 205 specimens, respectively. RESULTS In a univariate analysis, MSI-H (44 of 273; 16%) was associated with a longer disease-free survival (DFS; P = .038), but in a multivariate model adjusting for nodal involvement, histology, invasion, and grade of tumor, the association of MSI status with DFS did no longer reach statistical significance, though the risk estimate for microsatellite stability versus MSI-H tumors did not change much. Mutant TP53, found in 116 (53%) of 220 tumors, was associated with a shorter DFS, both in univariate (P = .009) and multivariate analyses (P = .018), whereas KRAS mutations (58 of 205; 28%) did not show any prognostic significance. CONCLUSION Both mutant TP53 and MSI-H seem to be prognostic indicators for disease-free survival, but only TP53 retains statistical significance after adjusting for clinical heterogeneity. Thus, in adjuvantly treated patients with stage III colon cancer, presence or absence of a TP53 mutation should be considered as a better predictor for DFS than MSI status.

18F-dihydroxyphenylalanine PET in patients with biochemical evidence of medullary thyroid cancer: relation to tumor differentiation.

Curative treatment for recurrent medullary thyroid cancer (MTC), diagnosed by rising serum calcitonin, is surgery, but tumor localization is difficult. Therefore, the value of 18F-dihydroxyphenylanaline PET (18F-DOPA PET), 18F-FDG PET, 99mTc-V-di-mercaptosulfuricacid (DMSA-V) scintigraphy, and MRI or CT was studied. Methods: Twenty-one patients with biochemical recurrent or residual MTC underwent 18F-DOPA PET, 18F-FDG PET, DMSA-V scintigraphy, and MRI or CT. Patient- and lesion-based sensitivities were calculated using a composite reference consisting of all imaging modalities. Results: In 76% of all patients with MTC, one or more imaging modalities was positive for MTC lesions. In 6 of 8 patients with a calcitonin level of <500 ng/L, imaging results were negative. In 15 patients with positive imaging results, 18F-DOPA PET detected 13 (sensitivity, 62%; with 4.6 lesions per patient [lpp]). Morphologic imaging (n = 19) was positive in 7 (sensitivity, 37%; 4.7 lpp), DMSA-V (n = 18) in 5 (sensitivity, 28%; 1.1 lpp), and 18F-FDG PET (n = 17) in 4 (sensitivity, 24%; 1.6 lpp). In a lesion-based analysis, 18F-DOPA PET detected 95 of 134 lesions (sensitivity, 71%), morphologic imaging detected 80 of 126 (sensitivity, 64%), DMSA-V detected 20 of 108 (sensitivity, 19%), and 18F-FDG PET detected 48 of 102 (sensitivity, 30%). In 2 of 3 patients with a calcitonin/carcinoembryonic antigen (CEA) doubling time of ≤12 mo, 18F-FDG PET performed better than 18FDOPA PET; in the third patient, 18F-FDG PET was not performed. Conclusion: MTC lesions are best detectable when serum calcitonin was >500 ng/L. 18F-DOPA PET is superior to 18F-FDG PET, DMSA-V, and morphologic imaging. With short calcitonin doubling times (≤12 mo), 18F-FDG PET may be superior.

Pregnancy and early-stage melanoma

Cutaneous melanomas are aggressive tumors with an unpredictable biologic behavior. It has been suggested that women who present with melanoma during pregnancy have a worse prognosis due to more aggressive behavior of the melanoma. The objective of the current study was to evaluate the long‐term effect of pregnancy on disease progression in women with Stage I–II melanoma.

Fluorodeoxyglucose Positron Emission Tomography for Evaluating Early Response During Neoadjuvant Chemoradiotherapy in Patients With Potentially Curable Esophageal Cancer

Background:Neoadjuvant chemoradiotherapy before surgery can improve survival in patients with potentially curable esophageal cancer, but not all patients respond. Fluorodeoxyglucose positron emission tomography (FDG-PET) has been proposed to identify nonresponders early during neoadjuvant chemoradiotherapy. The aim of the present study was to determine whether FDG-PET could differentiate between responding and nonresponding esophageal tumors early in the course of neoadjuvant chemoradiotherapy. Methods:This clinical trial comprised serial FDG-PET before and 14 days after start of chemoradiotherapy in patients with potentially curable esophageal carcinoma. Histopathologic responders were defined as patients with no or less than 10% viable tumor cells (Mandard score on resection specimen). PET response was measured using the standardized uptake value (SUV). Receiver operating characteristic analysis was used to evaluate the ability of SUV in distinguishing between histopathologic responders and nonresponders. Results:In 100 included patients, 64 were histopathologic responders. The median SUV decrease 14 days after the start of therapy was 30.9% for histopathologic responders and 1.7% for nonresponders (P = 0.001). In receiver operating characteristic analysis, the area under the curve was 0.71 (95% CI = 0.60–0.82). Using a 0% SUV decrease cutoff value, PET correctly identified 58 of 64 responders (sensitivity 91%) and 18 of 36 nonresponders (specificity 50%). The corresponding positive and negative predictive values were 76% and 75%, respectively. Conclusions:SUV decrease 14 days after the start of chemoradiotherapy was significantly associated with histopathologic tumor response, but its accuracy in detecting nonresponders was too low to justify the clinical use of FDG-PET for early discontinuation of neoadjuvant chemoradiotherapy in patients with potentially curable esophageal cancer.

Determinants of life expectancy in medullary thyroid cancer: age does not matter

Objective  In medullary thyroid cancer (MTC) age is considered an important prognostic factor but survival has never been properly adjusted for baseline mortality in the general population. We aimed to identify prognostic factors by analysing patients with MTC regarding life expectancy.

Positron emission tomography with F-18-fluorodeoxyglucose in a combined staging strategy of esophageal cancer prevents unnecessary surgical explorations

Distant metastases or local invasion are frequently found during the explorative phase of surgery for esophageal cancer. This study was performed to determine the rate of patients with incurable disease encountered during exploration and to examine the impact of preoperative staging, including positron emission tomography (PET), on the number of unnecessary explorations. The records of 203 patients with esophageal cancer who were eligible for curative resection were retrospectively reviewed. The surgical reports were analyzed to obtain the reasons for abandoning resection. Furthermore, the different staging modalities according to the related time interval were reviewed for each patient to analyze the influence of them on the number of explorations. After exploratory surgery, resection was abandoned in 78 of the 203 patients (38%) because of distant metastases (n = 59; 29%), metastatic spread and local irresectability (n = 5; 2%), and local irresectability (n = 14; 7%). In a logistic regression model with all preoperative staging modalities and the year of examination as independent variables, F-18-fluorodeoxyglucose (FDG)-PET) was the only modality that predicts intended curative resection in these patients (P < 0.001). In patients with esophageal cancer who are suitable for potentially curative surgery, resection was abandoned mainly because of distant metastases encountered during exploration. The addition of FDG-PET may have reduced the rate of unnecessary surgery in this group of patients.

Morbidity of the neck after head and neck cancer therapy

Studies on morbidity of the neck after head and neck cancer therapy are scarcely described.

Better survival in patients with esophageal cancer after surgical treatment in university hospitals: A plea for performance by surgical oncologists

BackgroundIn primary esophageal cancer, studies have frequently focused on surgical patients in an effort to link outcome to hospital- or surgeon-related experience, with operative mortality used as the main outcome measure. Many studies have found an inverse relationship between operative mortality and hospital volume and surgical expertise. This study aims to assess the influence of surgeon-related expertise and hospital volume on the relative survival of operated esophageal cancer patients.MethodsFrom January 1994 to January 2002, a total of 1149 consecutive patients with primary esophageal cancer were diagnosed in the region of the Comprehensive Cancer Center North-Netherlands. As a proxy for surgeon-related expertise, hospitals in this region were categorized into three types: university, teaching nonuniversity, and nonteaching hospitals. The influence of hospital type on the relative survival of operated patients was studied by a multivariate Poisson regression model.ResultsOf the 1149 patients, 18.5% underwent surgery. There was no evidence of selective referral for surgery between the three hospital types with regard to age, tumor stage, and location. For operated patients, the 5-year relative survival was 49.2% for the university hospital versus 32.6% and 27.3% for teaching nonuniversity and nonteaching hospitals, respectively (P = .0039). When adjusted for age, tumor stage, hospital volume and referral frequency, the relative excess risk of death for the university hospital was considerably lower at .57 (95% confidence interval, .29–1.12) compared with nonteaching hospitals and .43 (95% confidence interval, .24–.76) compared with teaching nonuniversity hospitals (P = .0126).ConclusionsIn our region, patients with esophageal cancer who underwent esophagectomy in the university hospital had a markedly better relative survival compared with those who underwent surgery at teaching nonuniversity and nonteaching hospitals, emphasizing the need for referral of esophageal surgery to centers with a greater experience.