Neoadjuvant Immunotherapy in Locally Advanced Mismatch Repair-Deficient Colon Cancer.

BACKGROUND: Mismatch repair-deficient (dMMR) tumors can be found in 10 to 15% of patients with nonmetastatic colon cancer. In these patients, the efficacy of chemotherapy is limited. The use of neoadjuvant immunotherapy has shown promising results, but data from studies of this approach are limited. METHODS: We conducted a phase 2 study in which patients with nonmetastatic, locally advanced, previously untreated dMMR colon cancer were treated with neoadjuvant nivolumab plus ipilimumab. The two primary end points were safety, defined by timely surgery (i.e., ≤2-week delay of planned surgery owing to treatment-related toxic events), and 3-year disease-free survival. Secondary end points included pathological response and results of genomic analyses. RESULTS: Of 115 enrolled patients, 113 (98%; 97.5% confidence interval [CI], 93 to 100) underwent timely surgery; 2 patients had surgery delayed by more than 2 weeks. Grade 3 or 4 immune-related adverse events occurred in 5 patients (4%), and none of the patients discontinued treatment because of adverse events. Among the 111 patients included in the efficacy analysis, a pathological response was observed in 109 (98%; 95% CI, 94 to 100), including 105 (95%) with a major pathological response (defined as ≤10% residual viable tumor) and 75 (68%) with a pathological complete response (0% residual viable tumor). With a median follow-up of 26 months (range, 9 to 65), no patients have had recurrence of disease. CONCLUSIONS: In patients with locally advanced dMMR colon cancer, neoadjuvant nivolumab plus ipilimumab had an acceptable safety profile and led to a pathological response in a high proportion of patients. (Funded by Bristol Myers Squibb; NICHE-2 ClinicalTrials.gov number, NCT03026140.).

Influence of Conversion and Anastomotic Leakage on Survival in Rectal Cancer Surgery; Retrospective Cross-sectional Study.

BACKGROUND: Conversion and anastomotic leakage in colorectal cancer surgery have been suggested to have a negative impact on long-term oncologic outcomes. The aim of this study in a large Dutch national cohort was to analyze the influence of conversion and anastomotic leakage on long-term oncologic outcome in rectal cancer surgery. METHODS: Patients were selected from a retrospective cross-sectional snapshot study. Patients with a benign lesion, distant metastasis, or unknown tumor or metastasis status were excluded. Overall (OS) and disease-free survival (DFS) were compared between laparoscopic, converted, and open surgery as well as between patients with and without anastomotic leakage. RESULTS: Out of a database of 2095 patients, 638 patients were eligible for inclusion in the laparoscopic, 752 in the open, and 107 in the conversion group. A total of 746 patients met the inclusion criteria and underwent low anterior resection with primary anastomosis, including 106 (14.2%) with anastomotic leakage. OS and DFS were significantly shorter in the conversion compared to the laparoscopic group (p = 0.025 and p = 0.001, respectively) as well as in anastomotic leakage compared to patients without anastomotic leakage (p = 0.002 and p = 0.024, respectively). In multivariable analysis, anastomotic leakage was an independent predictor of OS (hazard ratio 2.167, 95% confidence interval 1.322-3.551) and DFS (1.592, 1077-2.353). Conversion was an independent predictor of DFS (1.525, 1.071-2.172), but not of OS. CONCLUSION: Technical difficulties during laparoscopic rectal cancer surgery, as reflected by conversion, as well as anastomotic leakage have a negative prognostic impact, underlining the need to improve both aspects in rectal cancer surgery.

Anastomotic Leakage and Chronic Presacral Sinus Formation After Low Anterior Resection: Results From a Large Cross-sectional Study.

OBJECTIVES: Little is known about late detected anastomotic leakage after low anterior resection for rectal cancer, and the proportion of leakages that develops into a chronic presacral sinus. METHODS: In this collaborative snapshot research project, data from registered rectal cancer resections in the Dutch Surgical Colorectal Audit in 2011 were extended with additional treatment and long-term outcome data. Independent predictors for anastomotic leakage were determined using a binary logistic model. RESULTS: A total of 71 out of the potential 94 hospitals participated. From the 2095 registered patients, 998 underwent a low anterior resection, of whom 88.8% received any form of neoadjuvant therapy. Median follow-up was 43 months (interquartile range 35-47). Anastomotic leakage was diagnosed in 13.4% within 30 days, which increased to 20.0% (200/998) beyond 30 days. Nonhealing of the leakage at 12 months was 48%, resulting in an overall proportion of chronic presacral sinus of 9.5%. Independent predictors for anastomotic leakage at any time during follow-up were neoadjuvant therapy (odds ratio 2.85; 95% confidence interval 1.00-8.11) and a distal (≤3 cm from the anorectal junction on magnetic resonance imaging) tumor location (odds ratio 1.88; 95% confidence interval 1.02-3.46). CONCLUSIONS: This cross-sectional study of low anterior resection for rectal cancer in the Netherlands in 2011, with almost routine use of neoadjuvant radiotherapy, shows that one third of anastomotic leakages is diagnosed beyond 30 days, and almost half of the leakages eventually do not heal. Chronic presacral sinus is a significant clinical problem that deserves more attention.

Tumor heterogeneity on (18)F-FDG-PET/CT for response monitoring in non-small cell lung cancer treated with erlotinib.

Response monitoring using fluorodeoxyglucose positron emission tomography acquired together with low dose computed tomography (FDG-PET/CT) textural features has potential in targeted treatment with erlotinib in non-small cell lung cancer (NSCLC) patients. Patients with substantial decrease of metabolic activity during erlotinib treatment will probably benefit from continued treatment. However, various aspects of the method (quantification tools, cut-off values, etc.) need to be standardized before the software becomes widely available in a similar manner as standardized uptake value (SUV) measurements. Heterogeneity on FDG-PET/CT opened an additional window for innovation but simultaneously a new challenge for molecular hybrid imaging.

Prognostic value of pre-operative glucose-corrected maximum standardized uptake value in patients with non-small cell lung cancer after complete surgical resection and 5-year follow-up.

INTRODUCTION: In this study we evaluated the value of pre-operative glucose corrected maximum standard uptake value (GC-SUVmax) as prognostic factor in patients with early stage non-small cell lung cancer (NSCLC) after complete surgical resection. METHODS: This study was designed as a retrospectively evaluated single center study with prospective data registry. Inclusion criteria were: histologically proven stage I NSCLC, 18F-FDG-PET/CT scan prior to surgery, complete resection (R0) and follow up in our outpatient department. Exclusion criteria were: history of malignancy other than NSCLC, diabetes and (neo) adjuvant therapy. Follow up period was 5 years. RESULTS: Between 2006 and 2008 a total of 33 patients (16 males, 17 females) met the inclusion criteria. SUVmax and GC-SUVmax were strongly correlated (Spearman's ρ = 0.97). Five-year overall survival (OS) rate was 70 % (95 % CI = 56-87 %). Patients who died within 5 years of follow up had significantly higher pre-operative GC-SUVmax (median = 10.6, IQR = 8.3-14.4) than patients who were alive at 5-year follow up (median = 6.4, IQR = 3.0-9.8), p = 0.04. SUVmax showed similar differences: 10.4 (8-12.9) vs. 6.6 (3.0-8.8), p = 0.047. The area under the receiver-operating characteristic (ROC) curve at 5 years was 0.70 (95 % CI = 0.50-0.90) for GC-SUVmax and 0.71 (95 % CI = 0.51-0.91) for SUVmax (p = 0.75). CONCLUSION: Pre-operative FDG tumor uptake in patients with NSCLC is predictive for survival after complete surgical resection. GC-SUVmax, as an additional value to SUVmax, may better approach competitive inhibition of FDG and glucose in tumors, however, in this study this potential advantage, if any, was very small.

FDG-PET/CT response evaluation during EGFR-TKI treatment in patients with NSCLC.

Over recent years, [18F]-fluorodeoxyglucose positron emission tomography acquired together with low dose computed tomography (FDG-PET/CT) has proven its role as a staging modality in patients with non-small cell lung cancer (NSCLC). The purpose of this review was to present the evidence to use FDG-PET/CT for response evaluation in patients with NSCLC, treated with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI). All published articles from 1 November 2003 to 1 November 2013 reporting on 18F-FDG-PET response evaluation during EGFR-TKI treatment in patients with NSCLC were collected. In total 7 studies, including data of 210 patients were eligible for analyses. Our report shows that FDG-PET/CT response during EGFR-TKI therapy has potential in targeted treatment for NSCLC. FDG-PET/CT response is associated with clinical and radiologic response and with survival. Furthermore FDG-PET/CT response monitoring can be performed as early as 1-2 wk after initiation of EGFR-TKI treatment. Patients with substantial decrease of metabolic activity during EGFR-TKI treatment will probably benefit from continued treatment. If metabolic response does not occur within the first weeks of EGFR-TKI treatment, patients may be spared (further) unnecessary toxicity of ineffective treatment. Refining FDG-PET response criteria may help the clinician to decide on continuation or discontinuation of targeted treatment.

Timing of metabolic response monitoring during erlotinib treatment in non-small cell lung cancer.

UNLABELLED: The purpose of this study was to prospectively evaluate the timing of metabolic response monitoring with (18)F-FDG PET of (neoadjuvant) erlotinib treatment in patients with early-stage non-small cell lung cancer. METHODS: This study was designed as an open-label phase II trial performed in 4 hospitals in The Netherlands. Patients received preoperative erlotinib (150 mg) once daily for 3 wk. Response evaluation was performed after 4-7 d and at 3 wk with (18)F-FDG PET/CT scans. Tumor (18)F-FDG uptake and changes were measured as standardized uptake values (SUVs). The metabolic response was classified on the basis of European Organization for Research and Treatment of Cancer criteria (>25% decrease in the maximum SUV) and was compared with histopathologic regression as observed in the resection specimen. RESULTS: From December 2006 to November 2010, 60 patients with non-small cell lung cancer eligible for surgical resection were enrolled in this study. For 43 patients (18 men and 25 women), baseline (18)F-FDG PET/CT scans as well as both monitoring scans and histopathologic response monitoring were available. A partial metabolic response on (18)F-FDG PET/CT scans was observed for 10 patients (23%) after 1 wk and for 14 patients (33%) after 3 wk. Histopathologic examination revealed regression (necrosis of >50%) in 11 patients (26%). In these patients, the maximum SUV decreased by a mean of 17% within 1 wk and a mean of 31% at 3 wk. Seven patients were identified as responders within 1 wk. CONCLUSION: Response monitoring with (18)F-FDG PET/CT within 1 wk after the start of erlotinib treatment identified approximately 64% of histopathologic responders on the basis of European Organization for Research and Treatment of Cancer criteria.

(18)F-fluorodeoxyglucose positron emission tomography versus computed tomography in predicting histopathological response to epidermal growth factor receptor-tyrosine kinase inhibitor treatment in resectable non-small cell lung cancer.

PURPOSE: To prospectively evaluate diagnostic computed tomography (CT) and (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for identification of histopathologic response to neoadjuvant erlotinib, an epidermal growth factor receptor-tyrosine kinase inhibitor in patients with resectable non-small cell lung cancer (NSCLC). METHODS: This study was designed as an open-label phase 2 trial, performed in four hospitals in the Netherlands. Patients received preoperative erlotinib 150 mg once daily for 3 weeks. CT and FDG-PET/CT were performed at baseline and after 3 weeks of treatment. CT was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. FDG-PET/CT, tumor FDG uptake, and changes were measured by standardized uptake values (SUV). Radiologic and metabolic responses were compared to the histopathological response. RESULTS: Sixty patients were enrolled onto this study. In 53 patients (22 men, 31 women), the combination of CT, FDG-PET/CT, and histopathological evaluation was available for analysis. Three patients (6 %) had radiologic response. According to European Organisation for Research and Treatment of Cancer (EORTC) criteria, 15 patients (28 %) showed metabolic response. In 11 patients, histopathologic response (≥50 % necrosis) was seen. In predicting histopathologic response, relative FDG change in SUVmax showed more SUVmax decrease in the histopathologic response group (-32 %) versus the group with no pathologic response (-4 %) (p = 0.0132). Relative change in tumor size on diagnostic CT was similar in these groups with means close to 0. CONCLUSIONS: FDG-PET/CT has an advantage over CT as a predictive tool to identify histopathologic response after 3 weeks of EGFR-TKI treatment in NSCLC patients.

Can previous diagnostic examinations prevent preoperative angiographic assessment of the internal mammary perforators for (micro)surgical use?

BACKGROUND AND AIM: Preoperative assessment of the internal mammary artery perforating (IMAP) branches enhances IMAP-based reconstructive procedures. Conventionally, color-flow Doppler, selective catheter arteriography, or CT angiography is used for such assessment. We studied how often these examinations may be rendered superfluous by assessment of previously performed diagnostic examinations. METHODS: A radiologist and a plastic surgeon jointly assessed whether information on the dominant IMAP could sufficiently be obtained from the thoracic CT scans of 12 head and neck cancer patients and 12 breast cancer patients, and from the mammary MRI of 12 breast cancer patients. Secondly, we retrospectively assessed in how many of the 10 patients who underwent an IMAP-flap head and neck reconstruction, and in how many of the 10 women who consecutively underwent a deep inferior epigastric perforator (DIEP) flap mammary reconstruction such previous diagnostic examinations were available and informative regarding the level of the dominant perforator. RESULTS: All 24 CT scans and 11 of the 12 MRI scans sufficiently allowed assessment of the level of the dominant IMAP. Previous information had already been available in all 10 DIEP flap patients and 6 of the 10 IMAP-flap patients. The distribution of IMAP dominance over the intercostal levels on the scans differed from that found by cadaveric or intraoperative assessment. CONCLUSIONS: Previously performed diagnostic CT scans and MRI scans that included the parasternal region usually allow sufficient preoperative assessment of the internal mammary perforators for reconstructive procedures. We advocate re-assessment of such previous examinations before ordering additional angiography. Additionally, we suggest to include the parasternal region in diagnostic scans.

Initial assessment of chest X-ray in thoracic trauma patients: Awareness of specific injuries.

AIM: To compare the reported injuries on initial assessment of the chest X-ray (CXR) in thoracic trauma patients to a second read performed by a dedicated trauma radiologist. METHODS: By retrospective analysis of a prospective database, 712 patients with an injury to the chest admitted to the University Medical Center Utrecht were studied. All patients with a CXR were included in the study. Every CXR was re-evaluated by a trauma radiologist, who was blinded for the initial results. The findings of the trauma radiologist regarding rib fractures, pneumothoraces, hemothoraces and lung contusions were compared with the initial reports from the trauma team, derived from the original patient files. RESULTS: A total of 516 patients with both thorax trauma and an initial CXR were included in the study. After re-evaluation of the initial CXR significantly more lung contusions (53.3% vs 34.1%, P < 0.001), hemothoraces (17.8% vs 11.0%, P < 0.001) and pneumothoraces (34.4% vs 26.4%, P < 0.001) were detected. During initial assessment significantly more rib fractures were reported (69.8% vs 62.3%, P < 0.001). CONCLUSION: During the initial assessment of a CXR from trauma patients in the emergency department, a significant number of treatment-dictating injuries are missed. More awareness for these specific injuries is needed.

18F-FDG PET/CT as a staging procedure in primary stage II and III breast cancer: comparison with conventional imaging techniques.

The aim of the present study was to investigate if 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) outperforms conventional imaging techniques for excluding distant metastases prior to neoadjuvant chemotherapy (NAC) treatment in patients with stage II and III breast cancer. Second, we assessed the clinical importance of false positive findings. One hundred and fifty four patients with stage II or III breast cancer, scheduled to receive NAC, underwent an 18F-FDG PET/CT scan and conventional imaging, consisting of bone scintigraphy, ultrasound of the liver, and chest radiography. Suspect additional lesions at staging examination were confirmed by biopsy and histopathology and/or additional imaging. Metastases that were detected within 6 months after the PET/CT scan were considered evidence of occult metastasis, missed by staging examination. Forty-two additional distant lesions were seen in 25 patients with PET/CT and could be confirmed in 20 (13%) of 154 patients. PET/CT was false positive for 8 additional lesions (19%) and misclassified the presence of metastatic disease in 5 (3%) of 154 patients. In 16 (80%) of 20 patients, additional lesions were exclusively seen with PET/CT, leading to a change in treatment in 13 (8%) of 154 patients. In 129 patients with a negative staging PET/CT, no metastases developed during the follow-up of 9.0 months. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET/CT in the detection of additional distant lesions in patients with stage II or III breast cancer are 100, 96, 80, 100, and 97%, respectively. FDG PET/CT is superior to conventional imaging techniques in the detection of distant metastases in patients with untreated stage II or III breast cancer and is associated with a low false positive rate. PET/CT may be of additional value in the staging of breast cancer prior to NAC.

Validation of the Thorax Trauma Severity Score for mortality and its value for the development of acute respiratory distress syndrome.

BACKGROUND: The aim of the present study was to evaluate and to validate the Thorax Trauma Severity Score (TTSS) for mortality. METHODS: By database analysis 712 patients with an injury to the chest admitted to the Universal Medical Center Utrecht between 2000 and 2004 were studied. All patients with a score of ≥1 on the AISthorax were included in the study. The patients' file was evaluated for: TTSS, intensive care unit stay, days on ventilation, thorax trauma-related complications (eg, acute respiratory distress syndrome [ARDS]), total hospital stay, and mortality. RESULTS: Of the 516 patients included in the study, 140 (27%) developed thorax-related complications. The overall in-hospital mortality rate was 10%. The receiver operating characteristic curve for predicting mortality demonstrated an adequate discrimination by a value of 0.844. The TTSS was statistically significant higher in patients who died of thorax-related complications than in patients who died because of nonthorax-related complications and survivors (P < 0.001, confidence interval [CI] 95%). In patients who developed ARDS the TTSS was significant higher (P = 0.005, CI 95%). CONCLUSION: This study supports the use of the TTSS for predicting mortality in thoracic injury patients. Furthermore, the TTSS appears capable of predicting ARDS.

Detection of extra-axillary lymph node involvement with FDG PET/CT in patients with stage II-III breast cancer.

PURPOSE: The aim of this prospective study was to assess the incidence of extra-axillary lymph node involvement on baseline FDG PET/CT in patients with stage II-III breast cancer scheduled for neo-adjuvant chemotherapy. METHODS: Patients with invasive breast cancer of >3 cm and/or proven axillary lymph node metastasis were included for before neo-adjuvant chemotherapy. Baseline ultrasound of the infra- and supraclavicular regions was performed with fine-needle biopsy as needed. Subsequently FDG PET/CT was performed. All visually FDG-positive nodes were regarded as metastatic based on the previously reported high specificity of the technique. RESULTS: Sixty patients were included. In 17 patients (28%) extra-axillary lymph nodes were detected by FDG PET/CT, localised in an intra-mammary node (1 lymph node in 1 patient), mediastinal (2 lymph nodes in 2 patients), internal mammary chain (9 lymph nodes in 8 patients), intra- and interpectoral (6 lymph nodes in 4 patients), infraclavicular (5 lymph nodes in 4 patients) and in the contralateral axilla (3 lymph nodes in 2 patients). Ultrasound-guided cytology had detected extra-axillary lymph node involvement in seven of these patients, but was unable to detect extra-axillary nodes in the other 10 patients with positive extra-axillary lymph nodes on FDG PET/CT. Radiotherapy treatment was altered in 7 patients with extra-axillary involvement (12% of the total group). CONCLUSIONS: FDG PET/CT detected extra-axillary lymph node involvement in almost one-third of the patients with stage II-III breast cancer, including regions not evaluable with ultrasound. FDG PET/CT may be useful as an additional imaging tool to assess extra-axillary lymph node metastasis, with an impact on the adjuvant radiotherapy management.

Is 18F-FDG PET/CT useful for the early prediction of histopathologic response to neoadjuvant erlotinib in patients with non-small cell lung cancer?

UNLABELLED: Early prediction of treatment response is of value in avoiding the unnecessary toxicity of ineffective treatment. The objective of this study was to prospectively evaluate the role of integrated (18)F-FDG PET/CT for the early identification of response to neoadjuvant erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor. METHODS: From October 2006 to March 2009, 23 patients with non-small cell lung cancer eligible for surgical resection were evaluated for this study. Patients received preoperative erlotinib (150 mg) once daily for 3 wk. (18)F-FDG PET/CT was performed before and at 1 wk after the administration of erlotinib. Changes in tumor (18)F-FDG uptake during treatment were measured by standardized uptake values and assessed prospectively according to the criteria of the European Organization for Research and Treatment of Cancer. Patients with a decrease in standardized uptake values of 25% or more after 1 wk were classified as "metabolic responders." The metabolic response was compared with the pathologic response, obtained by histopathologic examination of the resected specimen. RESULTS: Following the (18)F-FDG PET/CT criteria of the European Organization for Research and Treatment of Cancer, 6 patients (26%) had a partial response within 1 wk, 16 patients (70%) had stable disease, and 1 patient (4%) had progressive disease. The median percentage of necrosis in the early metabolic responder group was 70% (interquartile range, 30%-91%), and the median percentage of necrosis in the nonresponder group was 40% (interquartile range, 20%-50%; P = 0.09). The kappa-agreement between the metabolic and pathologic responders was 0.55 (P = 0.008). CONCLUSION: The results of this study suggest that early during the course of epidermal growth factor receptor tyrosine kinase inhibitor therapy, (18)F-FDG PET/CT can predict response to erlotinib treatment in patients with non-small cell lung cancer.

Does thoracic injury impair the predictive value of base deficit in trauma patients?

INTRODUCTION: Base deficit (BD) has been shown to be a valuable indicator to be predictive of complications and mortality after trauma. Arterial carbon dioxide (PaCO(2)) may be influenced by thoracic injuries, potentially diminishing the predictive value of BD. Therefore, the aim of this study was to assess the predictive value of admission BD for mortality and complications in trauma patients with thoracic injuries. METHODS: By a prospective database analysis of patients with an injury to the chest admitted to the University Medical Center Utrecht between 2000 and 2004 were studied. All patients with a blood gas analyses were included. Absolute BD was used for analyses. Clinical outcome parameters were recorded. RESULTS: The BD was higher in the non-surviving patients compared to the survivors (7.5 vs. 3.8, p<0.001). Mortality rate of patients with an admission BD of >/=6 was increased in thoracic trauma patients (BD<6 mortality rate 7%, BD>/=6 mortality rate 27%; p<0.001). In patients who required ICU admittance the BD was increased compared to patients without ICU admission (5.2 vs. 2.9, p<0.001). Within the subgroup of patients admitted to the ICU, the BD was higher in patients who required ventilation (3.8 vs. 5.5, p=0.025). Patients who developed chest related complications had increased BD compared with those without complications (4.9 vs. 4.0, p=0.025), the BD was particularly increased in patients who developed acute respiratory distress syndrome (ARDS) (4.1 vs. 6.4, p=0.004). Carbon dioxide (PaCO(2)) showed a predictive value for mortality (44 vs. 53, p<0.001), ICU admission (42 vs. 46, p=0.003) and hospital stay. CONCLUSION: Admission BD is a predictive factor in thoracic trauma patients for mortality and chest related complications. Furthermore it is a predictive factor for ICU admission, required ventilation and hospital stay. The use of BD in thoracic trauma patients can potentially identify patients who require additional monitoring or early aggressive therapy.

Utility of preoperative 18F-FDG PET/CT and brain MRI in melanoma patients with palpable lymph node metastases.

BACKGROUND: The aims of this prospective study were to determine the diagnostic value of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) and brain MRI in melanoma patients with palpable lymph node metastases and to assess the impact of these imaging modalities on their management. MATERIALS AND METHODS: Between October 2006 and March 2009, PET/CT and brain MRI were performed in 70 melanoma patients with palpable nodal lymph node metastases and without evidence of systemic dissemination after physical examination. Hypermetabolic PET/CT lesions were examined by histology or cytology or were imaged further and followed if no pathology confirmation could be obtained. RESULTS: PET/CT findings changed the intended regional node dissection in 26 patients (37%). PET/CT was false negative in 4 patients (6%) and false positive in 1 (1%). This resulted in a sensitivity of 87%, specificity of 98%, accuracy of 93%, positive predictive value of 96%, and negative predictive value of 91%. MRI revealed brain metastases in 5 patients (7%). The overall survival of patients without additional lesions on PET/CT was 84% after 2 years, which was better than the 56% in patients with additional metastases (P < .001). CONCLUSIONS: PET/CT has an 87% sensitivity and 98% specificity in the detection of other metastases in melanoma patients with palpable lymph node involvement. PET/CT leads to a change in the planned regional node dissection in 37% of the patients in this study. MRI revealed brain metastases in 5 patients (7%). PET/CT findings correlate with survival.

Feasibility of FDG PET/CT to monitor the response of axillary lymph node metastases to neoadjuvant chemotherapy in breast cancer patients.

PURPOSE: The aim of this study was to assess the accuracy of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT to visualize lymph node metastases before the start of neoadjuvant chemotherapy and to determine how often the visualization is sufficiently prominent to allow monitoring of the axillary response. METHODS: Thirty-eight patients with invasive breast cancer of >3 cm and/or lymph node metastasis underwent FDG PET/CT before neoadjuvant chemotherapy. The results of the FDG PET/CT were compared with those from ultrasonography with fine-needle aspiration (FNA) cytology or sentinel node biopsy. Patients suitable for response monitoring of the axilla were defined as having either a maximum standardized uptake value (SUV(max)) >or= 2.5 or a tumour to background ratio >or=5 in the most intense lymph node. RESULTS: The sensitivity and specificity of FDG PET/CT in detecting axillary involvement were 97 and 100%, respectively. No difference existed between the SUV(max) of the primary tumour and that from the related most intense lymph node metastasis. Moreover, the mean tumour to background ratio was 90% higher in the lymph nodes compared to the primary tumour (p = 0.006). Ninety-three per cent of the patients had sufficient uptake in the lymph nodes to qualify for subsequent response monitoring of the axilla. A considerable distinction in metabolic activity was observed between the different subtypes of breast cancer. The mean SUV(max) in lymph node metastases of oestrogen receptor (ER)-positive, triple-negative and human epidermal growth factor receptor 2 (HER2)-positive tumours was 6.6, 11.6 and 6.6, respectively. CONCLUSION: The high accuracy in visualizing lymph node metastases and the sufficiently high SUV(max) and tumour to background ratio at baseline suggest that it is feasible to monitor the axillary response with FDG PET/CT, especially in triple-negative tumours.

Utility of FDG PET/CT and brain MRI in melanoma patients with increased serum S-100B level during follow-up.

BACKGROUND: The serum level of the S-100B protein is increasingly used as a tumor marker in melanoma patients. The aims of this study were to assess the clinical relevance of increased S-100B during follow up of high-risk melanoma patients and to determine the value of subsequent whole-body PET/CT and brain MRI. MATERIALS AND METHODS: A retrospective analysis was performed of all 46 melanoma patients with a normal history and physical examination who were found to have an elevated serum S-100B level (> or =0.10 microg/L) during follow-up between August 2006 and March 2009. Suspicious lesions on FDG PET/CT were biopsied for histological or cytological confirmation or were imaged further and followed if no pathology confirmation could be obtained. RESULTS: The positive predictive value of an elevated serum S-100B was 50%. PET/CT revealed hypermetabolic lesions in 27 of the 46 patients (59%). PET/CT was never false negative as confirmed by median follow-up of 1 year but was false positive in 4 patients. MRI revealed brain metastases in 1 patient (2%). Of the 23 patients with a true positive PET/CT scan, 6 (26%) received surgical treatment with curative intent; the other 17 (74%) received palliative treatment or supportive care. The survival of patients with a normal PET/CT was longer than patients with a positive PET/CT (P = .002). CONCLUSIONS: An elevated serum S-100B during follow-up of high-risk melanoma patients has a modest 50% positive predictive value for recurrent disease. Subsequent PET/CT and MRI can identify patients with recurrent disease.

Prevention of brown adipose tissue activation in 18F-FDG PET/CT of breast cancer patients receiving neoadjuvant systemic therapy.

UNLABELLED: (18)F-FDG uptake in brown adipose tissue (BAT) can complicate interpretation and quantification of PET images, especially in regions of possible lymph node metastases such as the axilla and the mediastinum. The aim of this study was to prospectively evaluate the effect of patient preparation using a single oral dose of diazepam and controlled indoor temperature to prevent (18)F-FDG uptake in BAT in breast cancer patients referred for monitoring of therapy response with (18)F-FDG PET. METHODS: During the fall and winter months, 53 patients referred for (18)F-FDG PET/CT of breast cancer were included. A cohort of 25 patients was imaged without an intervention, and a second cohort of 28 patients was prepared according to a new protocol that included 10 mg of diazepam and adequate indoor temperature. The generated images were visually assessed for the presence of (18)F-FDG at the location of fat-density tissue on CT images using a 4-point scale. RESULTS: In the cohort without intervention, relevant (18)F-FDG uptake in BAT was identified in 4 patients (16%); in the cohort prepared according to the proposed protocol, in only 1 patient (4%). The mean score of BAT (18)F-FDG uptake evaluated with the 4-point system was 0.04 in the group treated according to the new protocol and 0.16 in the group treated according to the previous protocol. CONCLUSION: In the clinically relevant group of breast cancer patients, (18)F-FDG uptake in BAT can be reduced by a single oral administration of diazepam combined with controlled room temperature in resting rooms.

Predicting early chemotherapy response with technetium-99m methoxyisobutylisonitrile SPECT/CT in advanced non-small cell lung cancer.

PURPOSE: The purpose of this study is to examine the prognostic value of prechemotherapy technetium-99m methoxyisobutylisonitrile ((99m)Tc-MIBI) uptake with single photon emission computed tomography/computed tomography (SPECT/CT) in relation to tumor size change measured by CT. METHODS: Eleven patients with stage IIIB/IV non-small cell lung cancer (NSCLC) underwent (99m)Tc-MIBI SPECT/CT within 24 h before starting platinum-containing chemotherapy. Following the Response Evaluation Criteria in Solid Tumors guidelines, 20 lesions from the 11 patients were available for evaluation. Maximum (C (max)) and mean (C (mean)) MIBI counts were calculated for each lesion. One-dimensional (1D; longest diameter) and two-dimensional (2D; area of the largest transverse surface) tumor measurements were assessed by two observers on the diagnostic CT and the response assessment CT after two cycles of chemotherapy. RESULTS: Bland-Altman analysis demonstrated no clinically significant bias between the observers. A solid correlation was found between (99m)Tc-MIBI C (mean) and change in the longest diameter (1D change) of the target lesion (rho = -0.62) using Spearman's rank correlation test. C (mean) also correlated negatively with change in the area of the largest transverse surface (2D change) of the target lesion (rho = -0.53). Furthermore, a correlation was established between (99m)Tc-MIBI C (max) and 1D change (rho = -0.56) in tumor size as well, though less strongly when compared to its C (mean) counterpart. CONCLUSIONS: Our series demonstrated solid, negative correlations between prechemotherapy (99m)Tc-MIBI uptake and tumor size change measured by CT for advanced NSCLC, particularly with C (mean) and 1D change.