Deep and lasting response and acquired resistance to BRAFV600E targeting in a low-grade ovarian cancer patient.

The treatment of BRAFV600E mutant melanoma has been revolutionized by BRAF inhibitors. Furthermore, the BRAF/MEK combination has shown further improvement in clinical outcomes in advanced and in adjuvant melanoma patients. In low-grade ovarian tumors, BRAF inhibitor use has been also proposed. Here we present a patient with an excellent, lasting response to BRAF therapy alone. At first progression, after more than two years on BRAF monotherapy, we could not identify any molecular mechanisms explaining resistance. After a switch to dual BRAF/MEK therapy, the patient responded. However, despite the initial response clinical the patient again progressed, this time with the appearance of a KRAS G12C mutation, which could not be overcome by BRAF/MEK therapy. We provide evidence that BRAF inhibitor alone can be highly beneficial in BRAF mutant low-grade ovarian tumors and the resistance mechanisms are similar to that of other BRAF mutant tumors, including in melanoma.

Utility of a modified distress thermometer in screening COVID-19 patients for psychological distress: a prospective Egyptian study.

BACKGROUND: The National Comprehensive Cancer Network (NCCN) has adopted the distress thermometer (DT) as one of the best-known distress-screening instruments. We have adopted a modified version of the NCCN distress thermometer. We questioned if this modified DT (m-DT) could be utilized for measuring the prevalence of psychological distress among COVID-19 patients. METHODS: The prospective study included 2 phases; modification of the original DT and its associated problem list (PL), and evaluation of this m-DT in measuring the prevalence of psychological distress among COVID-19 patients. Egyptian adult subjects with suspected or confirmed cases of COVID-19 at 2 University Hospitals were enrolled. Binary logistic regression tests were carried out to explore the association between the m-DT cut-off scores of 4 and the clinical variables. RESULTS: One hundred sixty-nine (60.4%) patients experienced significant distress (m-DT cut off score ≥4). Logistic regression showed that occupation, presence of special habits, length of quarantine time, worry, cough, shortness of breath, and fever, were independent factors associated with significant distress in COVID-19 patients. CONCLUSION: With the modified distress thermometer (m-DT), 60% of Egyptian COVID-19 patients experienced significant distress. This distress was significantly related to age, marital status, occupation, presence or absence of special habits, and length of the quarantine time. With m-DT, the current study had identified worry, being a health-care worker, shortness of breath, fever, length of quarantine time, presence of special habits, and cough as independent factors associated with significant distress in COVID-19 patients. Further studies are warranted.

Is it the time to implement the routine use of distress thermometer among Egyptian patients with newly diagnosed cancer?

BACKGROUND: The distress thermometer (DT) is an effective tool for identifying distress among cancer patients worldwide. However, DT has not been studied in Egyptian patients. We aimed to study the prevalence of distress among Egyptian patients with different types of cancers using DT. METHODS: A total of 550 patients with newly diagnosed hematological and solid cancers who were followed up at 3 Oncology Centers in Egypt were enrolled. They completed a sociodemographic and clinical status questionnaire, the DT and the Problem List (PL) scale. RESULTS: At a DT cut-off score of ≥4, 46% of patients had significant distress, which was related to the tumor site and stage. The most frequent problems reported were treatment decision (64.4%), worry (47%), and fears (44.5%). In univariate logistic regression analysis, participants who had significant distress described 23 out of 36 problems in the practical, family, emotional, and physical areas. After adjustment to sociodemographic and clinical characteristics, multivariable analysis confirmed that insurance, depression, fear, sadness, worry, loss of interest in usual activity, and sleep were independent factors associated with significant distress in cancer patients. CONCLUSIONS: Almost half of Egyptian patients newly diagnosed with cancer reported significant distress. Those who had significant distress described extra problems in the practical, family, emotional, and physical areas. We recommend the routine use of DT for screening Egyptian patients with cancer, as well as the involvement of the psycho-oncology and social services, at the time of their initial diagnosis.

[Usefulness of 18F-FDG-PET/CT for diagnosis of large vessel vasculitis]. / Utilité du 18F-FDG-PET/CT dans le diagnostic des vasculites des grands vaisseaux.

Positron emission tomography with 18F-fluorodesoxyglucose allows to locate pathological foci expressing a high metabolism. Originally shown in the investigation of neoplasia, this procedure is increasingly used as a new tool to search for inflammatory syndromes. Systemic vasculitis is a complex disorder, often manifested by non specific symptoms. Diagnosis at early stages allows early treatment, which may prevent progression to later complications. Through a case report and a review of the literature, this article describes the important role of PET/CT for the diagnosis when traditional tests remain unsuccessful.

Bucket-handle tear of the triangular fibrocartilage complex: case report of a complex peripheral injury with separation of the distal radioulnar ligaments from the articular disc.

Palmer previously proposed a classification system of triangular fibrocartilage complex (TFCC) injuries that proved to be useful in directing clinical management. However, dorsal peripheral tears (variants of class 1C) were not described and have rarely been reported in the literature since. We herewith present a rare case of bucket-handle tear of the TFCC. To our knowledge, this is the first case demonstrating partial separation of both the palmar and dorsal distal radioulnar ligaments (DRULs) from the articular disc. The particular wrist magnetic resonance (MR) arthrographic findings of this unusual complex peripheral TFCC tear (a variant of both class 1B and 1C) were nicely appreciated upon sagittal reformatted images.

Forced diuresis improves the diagnostic accuracy of 18F-FDG PET in abdominopelvic malignancies.

UNLABELLED: Our aim was to evaluate the role of forced diuresis in improving the diagnostic accuracy of abdominopelvic (18)F-FDG PET. METHODS: Thirty-two patients were enrolled. Besides the presence of known intravesical tumors or undefined renal lesions on the initial PET scan, the inclusion criterion was the appearance of indeterminate or equivocal (18)F-FDG foci that extended along the course of the urinary tract and could not confidently be separated from urinary activity. For each patient, a second abdominopelvic PET study was performed after intravenous injection of 0.5 mg of furosemide per kilogram of body weight (maximum, 40 mg) coupled with parenteral infusion of physiologic saline. RESULTS: Forced diuresis coupled with parenteral hydration eliminated any significant (18)F-FDG activity from the lower urinary tract in 31 (97%) of 32 patients after the bladder had been voided 3 successive times. Twelve intravesical lesions were visualized with outstanding clarity, whereas radiologic suspicion of locally recurrent bladder tumors was ruled out in 3 patients. Among 14 indeterminate or equivocal extravesical foci, 7 were deemed of no clinical value because they disappeared after furosemide challenge, whereas 7 persisting foci were proven to be true-positive PET findings. The performance of (18)F-FDG PET in characterizing 3 renal-space-occupying lesions could not be improved by our protocol. CONCLUSION: Furosemide challenge has the potential to noninvasively resolve the inherent (18)F-FDG contrast handicap in the lower urinary tract.

Occult lung infarction may induce false interpretation of 18F-FDG PET in primary staging of pulmonary malignancies.

PURPOSE: The aim of the present report is to describe abnormal (18)F-fluorodeoxyglucose (FDG) accumulation patterns in the pleura and lung parenchyma in a group of lung cancer patients in whom lung infarction was present at the time of positron emission tomography (PET). METHODS: Between November 2002 and December 2003, a total of 145 patients (102 males, 43 females; age range 38-85 years) were subjected to whole-body FDG PET for initial staging (n=117) or restaging (n=11) of lung cancer or for evaluation of solitary pulmonary nodules (n=17). Of these patients, 24 displayed abnormal FDG accumulation in the lung parenchyma that was not consistent with the primary lesion under investigation (ipsilateral n=12, contralateral n=9 or bilateral n=3). Without correlative imaging, this additional FDG uptake would have been considered indeterminate in differential diagnosis. RESULTS: Of the 24 patients who were identified as having such lesions, six harboured secondary tumour nodules diagnosed as metastases, while in three the diagnosis of a synchronous second primary lung tumour was established. Additionally, nine patients were identified as having post-stenotic pneumonia and/or atelectasis (n=6) or granulomatous lung disease (n=3). In the remaining six (4% of all patients), a diagnosis of recent pulmonary embolism that topographically matched the additional FDG accumulation (SUV(max) range 1.4-8.6, mean 3.9) was made. Four of these six patients were known to have pulmonary embolism, and hence false positive interpretation was avoided by correlating the PET findings with those of the pre-existing diagnostic work-up. The remaining two patients were harbouring small occult infarctions that mimicked satellite nodules in the lung periphery. Based on histopathological results, the abnormal FDG accumulation in these two patients was attributed to the inflammatory reaction and tissue repair associated with the pathological cascade of pulmonary embolism. CONCLUSION: In patients with pulmonary malignancies, synchronous lung infarction may induce pathological FDG accumulation that can mimic active tumour manifestations. Identifying this potential pitfall may allow avoidance of false positive FDG PET interpretation.

Significance of incidental 18F-FDG accumulations in the gastrointestinal tract in PET/CT: correlation with endoscopic and histopathologic results.

UNLABELLED: This study was undertaken to identify the clinical value of incidentally detected lesions (IDLs) in the gastrointestinal tract (GIT) with (18)F-FDG PET/CT. METHODS: The reported database of 3,281 patients who underwent partial-body (18)F-FDG PET/CT scans from April 2001 to September 2003 was reviewed. Patients with incidental (18)F-FDG accumulations in the GIT that were associated with concomitant abnormal soft-tissue density or wall thickening on the native CT were evaluated. Incidental PET/CT findings were correlated with endoscopic and histopathologic results. RESULTS: According to our selection criteria, 98 (3%) of the 3,281 patients had an IDL of the GIT on (18)F-FDG PET/CT. Correlative endoscopic findings were available in 69 (70%) of 98 patients. Of these, 13 patients (19%) were harboring newly occurring cancers of the GIT in addition to preexisting aerodigestive tract tumors (n = 12) and malignant melanoma (n = 1). Twenty-nine (42%) patients were identified with precancerous lesions, such as advanced colonic adenomas (n = 27), Barrett's esophagus (n = 1), and intestinal metaplasia of the gastric mucosa (n = 1). Inflammatory and other benign GIT lesions were detected in 12 (17%) and 6 (8%) patients, respectively. In 9 (13%) patients, PET/CT was false-positive, showing normal findings in subsequent endoscopic examinations. In 20 (28%) of 69 patients, PET/CT findings had a relevant impact on the clinical management. Twenty-nine (30%) of the 98 patients were not subject to a further endoscopic examination because of the extent and nature of the primary tumor (n = 17), loss to follow-up (n = 7), death shortly after PET (n = 3), and patient unwillingness (n = 2). CONCLUSION: Although IDLs of the GIT on (18)F-FDG PET/CT scans are found only in about 3% of cases, they are associated with a substantial risk of an underlying cancerous or precancerous lesion. Early identification of these occult lesions may have a major impact on the patients' management and outcome.

Whole-body (18)F-FDG PET improves the management of patients with small cell lung cancer.

UNLABELLED: The aim of this study was to evaluate the impact of whole-body (18)F-FDG PET on staging and managing patients with small cell lung cancer (SCLC). METHODS: The treatment records of 42 consecutive patients (27 men, 15 women; mean age, 62 y; age range, 45-83 y) with SCLC were reviewed. Whole-body (18)F-FDG PET was performed for initial staging in 24 patients and for restaging after chemotherapy or radiation treatment in 20 patients. Two patients of the initial staging group were restaged with PET after therapy. PET findings were correlated with clinical and radiologic findings (CT of the chest and abdomen, bone scan, and CT or MRI of the brain). The impact of PET on staging and management decisions was determined. RESULTS: For 12 of 42 patients (29%), PET results changed the patient's management. In 8 patients (19%), PET resulted in a change of radiation therapy because of the detection of previously unknown tumor foci. Adjuvant radiation therapy was cancelled in 3 patients. A change of radiation field and volume was necessary in 5 patients. In 1 patient, PET results excluded extensive disease, which permitted surgical resection of the tumor. Chemotherapy was discontinued in 2 patients and restarted in 1 patient on the basis of the PET findings. In 5 patients (12%), PET excluded malignancy as the suspicious lesions found with conventional cross-sectional imaging did not take up (18)F-FDG. CONCLUSION: The results of this study show that (18)F-FDG PET has a major impact on the management of patients with SCLC, influencing both the stage and the management in 29% of patients. PET is a highly valuable tool for accurate target definition of radiation treatment by reducing the probability of overlooking involved areas.

Staging of non-small-cell lung cancer with integrated positron-emission tomography and computed tomography.

BACKGROUND: We compared the diagnostic accuracy of integrated positron-emission tomography (PET) and computed tomography (CT) with that of CT alone, that of PET alone, and that of conventional visual correlation of PET and CT in determining the stage of disease in non-small-cell lung cancer. METHODS: In a prospective study, integrated PET-CT was performed in 50 patients with proven or suspected non-small-cell lung cancer. CT and PET alone, visually correlated PET and CT, and integrated PET-CT were evaluated separately, and a tumor-node-metastasis (TNM) stage was assigned on the basis of image analysis. Nodal stations were identified according to the mapping system of the American Thoracic Society. The standard of reference was histopathological assessment of tumor stage and node stage. Extrathoracic metastases were confirmed histopathologically or by at least one other imaging method. A paired sign test was used to compare integrated PET-CT with the other imaging methods. RESULTS: Integrated PET-CT provided additional information in 20 of 49 patients (41 percent), beyond that provided by conventional visual correlation of PET and CT. Integrated PET-CT had better diagnostic accuracy than the other imaging methods. Tumor staging was significantly more accurate with integrated PET-CT than with CT alone (P=0.001), PET alone (P<0.001), or visual correlation of PET and CT (P=0.013); node staging was also significantly more accurate with integrated PET-CT than with PET alone (P=0.013). In metastasis staging, integrated PET-CT increased the diagnostic certainty in two of eight patients. CONCLUSIONS: Integrated PET-CT improves the diagnostic accuracy of the staging of non-small-cell lung cancer.

[18F]-Fluorodeoxyglucose positron emission tomography in patients with suspected recurrence of breast cancer.

AIM: To evaluate the role of [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients presenting with a suspicion of breast cancer relapse after primary treatment. MATERIALS AND METHODS: Sixty consecutive female patients with clinical (n=35) or radiological (n=25) suspicion of breast cancer recurrence were evaluated by FDG-PET. Positive PET findings were further evaluated by histological examination or clinical and radiological follow-up. In 25 patients, the serum tumor marker (CA 15-3) status was compared to the PET results. RESULTS: Disease relapse was proven in 40 patients. Additionally, in three patients a second cancer was diagnosed with (n=1), and without (n=2) concomitant disease relapse. PET missed local recurrence in three patients, and was false positive in another four. In patient-based analysis, the overall sensitivity, specificity, and accuracy were 89%, 84%, and 87%, and 100%, 97%, and 98% for locoregional recurrence and distant metastases, respectively. FDG-PET was more sensitive than the serum tumor marker CA 15-3 in detecting relapsed breast cancer. CONCLUSION: FDG-PET is a valuable tool in the follow-up of patients with breast cancer.

Respiration-induced attenuation artifact at PET/CT: technical considerations.

Combined positron emission tomographic (PET)/computed tomographic (CT) scanners allow the use of CT data for attenuation correction of PET images. Eight patients with cancer underwent PET/CT scanning. Transmission scanning was performed with conventional attenuation correction and with CT scanning during maximum inspiration and normal expiration. Image quality was visually compared and fluorine 18 activities were measured in volumes of interest in the lung and myocardium. Analysis of variance for repeated measures revealed a significant decrease (P =.0001) in measured activities between PET images corrected with CT data acquired during maximum inspiration and those corrected with the conventional attenuation correction method or with CT data acquired during normal expiration. Deep inspiration during CT can result in severe deterioration in the final PET image.

Accuracy of image coregistration of pulmonary lesions in patients with non-small cell lung cancer using an integrated PET/CT system.

UNLABELLED: The purpose of this study was to evaluate the accuracy of image coregistration of PET and CT (PET/CT) images in patients with lung lesions and the influence of the breathing protocol during CT. METHODS: Seventy-five patients with a solitary and well-circumscribed pulmonary lesion (non-small cell lung cancer; size, 10-30 mm) underwent PET/CT on a combined scanner. CT was acquired during shallow breathing in 37 patients and during normal expiration (i.e., the level reached when the patient exhaled without forcing expiration and then held the breath) in 38 patients. The volume of interest of each lesion was defined separately on PET and CT images, and the geometric center of gravity (COG) was assessed. The distance of COGs between the PET image and the CT image was measured. All lesions were classified according to 4 lung regions: apical, peripheral, central, and lung base. The mismatch between COG(PET) and COG(CT) was compared between regions and patient groups using a 2-way ANOVA with the Bonferroni-Dunn test for post hoc comparisons. RESULTS: The range of COG distance between PET and CT was 1.7-5.4 mm in the apex, 0.5-14.7 mm in the periphery, 0.7-5.9 mm centrally, and 2.9-11.3 mm in the lung base. The match between PET and CT was significantly better in patients who had the CT scan obtained during normal expiration than in patients who performed shallow breathing during CT scanning (P = 0.024). No reciprocal effects were found (interaction P = 0.76). The mismatch of lesions depends significantly on lung region (P < 0.0001). Post hoc analysis showed a significant difference between the upper 2 regions and the lower 2 regions (all P < or = 0.002) but not between the apex and the central region (P = 0.95) and between the peripheral region and the lung base (P = 0.15). The lesion size had no influence on the COG mismatch. CONCLUSION: The match of lung lesions in coregistered PET/CT images is better when acquiring the CT scan during normal expiration. The coregistration accuracy is better in the upper and central parts of the lung. The normal expiration protocol is suggested to be superior to shallow breathing during CT scanning.

Recurrent laryngeal nerve palsy in patients with lung cancer: detection with PET-CT image fusion -- report of six cases.

Positron emission tomography (PET) with fluorodeoxyglucose (FDG) was performed for preoperative staging of lung cancer. In six of 184 patients, there was an intense FDG accumulation in the lower anterior neck. Fusion of PET and computed tomographic images revealed that the focal FDG uptake was localized in the internal laryngeal muscles. This finding was a result of compensatory laryngeal muscle activation caused by contralateral recurrent laryngeal nerve palsy due to direct nerve invasion by lung cancer of the left mediastinum or lung apices. The knowledge of this pitfall is important to avoid false-positive PET results.

CT vs 68Ge attenuation correction in a combined PET/CT system: evaluation of the effect of lowering the CT tube current.

With the introduction of combined positron emission tomography/computed tomography (PET/CT) systems, several questions have to be answered. In this work we addressed two of these questions: (a) to what value can the CT tube current be reduced while still yielding adequate maps for the attenuation correction of PET emission scans and (b) how do quantified uptake values in tumours derived from CT and germanium-68 attenuation correction compare. In 26 tumour patients, multidetector CT scans were acquired with 10, 40, 80 and 120 mA (CT10, CT40, CT80 and CT120) and used for the attenuation correction of a single FDG PET emission scan, yielding four PET scans designated PET(CT10)-PET(CT120). In 60 tumorous lesions, FDG uptake and lesion size were quantified on PET(CT10)-PET(CT120). In another group of 18 patients, one CT scan acquired with 80 mA and a standard transmission scan acquired using 68Ge sources were employed for the attenuation correction of the FDG emission scan (PET(CT80), PET(68Ge)). Uptake values and lesion size in 26 lesions were compared on PET(CT80) and PET(68Ge). In the first group of patients, analysis of variance revealed no significant effect of CT current on tumour FDG uptake or lesion size. In the second group, tumour FDG uptake was slightly higher using CT compared with 68Ge attenuation correction, especially in lesions with high FDG uptake. Lesion size was similar on PET(CT80) and PET(68Ge). In conclusion, low CT currents yield adequate maps for the attenuation correction of PET emission scans. Although the discrepancy between CT- and 68Ge-derived uptake values is probably not relevant in most cases, it should be kept in mind if standardised uptake values derived from CT and 68Ge attenuation correction are compared.

PET-CT image co-registration in the thorax: influence of respiration.

Because anatomical information on fluorine-18 fluorodeoxyglucose (FDG) whole-body positron emission tomography (PET) images is limited, combination with structural imaging is often important. In principle, software co-registration of PET and computed tomography (CT) data or dual-modality imaging using a combined PET-CT camera has an important role to play, since "hardware-co-registered" images are thereby made available. A major unanswered question is under which breathing protocol the respiration level in the CT images of a patient will best match the PET images, which represent summed images over many breathing cycles. To address this issue, 28 tumour patients undergoing routine FDG PET examinations were included in this study. In ten patients, PET and CT were performed using a new combined high-performance in-line PET-CT camera without the need for repositioning of the patient, while in 18 patients imaging was performed on separate scanners located close to each other. CT was performed at four respiration levels: free breathing (FB), maximal inspiration (MaxInsp), maximal expiration (MaxExp) and normal expiration (NormExp). The following distances were measured: (a) between a reference point taken to be the anterior superior edge of intervertebral disc space T10-11 and the apex of the lung, (b) from the apex of the lung to the top of the diaphragm, (c) from the apex of the lung to the costo-diaphragmatic recess and (d) from the reference point to the lateral thoracic wall. Differences between CT and corresponding PET images in respect of these distances were compared. In addition, for each of 15 lung tumours in 12 patients, changes in tumour position between PET and CT using the same protocol were measured. CT during NormExp showed the best fit with PET, followed by CT during FB. The mean differences in movement of the diaphragmatic dome on CT during NormExp, FB, MaxInsp and MaxExp, as compared with its level on PET scan, were, respectively, 0.4 mm (SD 11.7), -11.6 mm (13.3), -44.4 mm (25.5) and -9.5 mm (25.6). CT acquired in MaxExp and MaxInsp is not suitable for image co-registration owing to the poor match of images in MaxInsp and because of difficulties with patient performance in MaxExp. With reference to lung lesions, NormExp showed the best results, with a higher probability of a good match and a smaller range of measured values in comparison with FB. Image misregistration in combined PET-CT imaging can be minimized to dimensions comparable to the spatial resolution of modern PET scanners. For PET-CT image co-registration, the use of a normal expiration breath-hold protocol for CT acquisition is recommended, independent of whether combined PET-CT systems or stand-alone systems are used.

Head and neck imaging with PET and PET/CT: artefacts from dental metallic implants.

Germanium-68 based attenuation correction (PET(Ge68)) is performed in positron emission tomography (PET) imaging for quantitative measurements. With the recent introduction of combined in-line PET/CT scanners, CT data can be used for attenuation correction. Since dental implants can cause artefacts in CT images, CT-based attenuation correction (PET(CT)) may induce artefacts in PET images. The purpose of this study was to evaluate the influence of dental metallic artwork on the quality of PET images by comparing non-corrected images and images attenuation corrected by PET(Ge68) and PET(CT). Imaging was performed on a novel in-line PET/CT system using a 40-mAs scan for PET(CT) in 41 consecutive patients with high suspicion of malignant or inflammatory disease. In 17 patients, additional PET(Ge68) images were acquired in the same imaging session. Visual analysis of fluorine-18 fluorodeoxyglucose (FDG) distribution in several regions of the head and neck was scored on a 4-point scale in comparison with normal grey matter of the brain in the corresponding PET images. In addition, artefacts adjacent to dental metallic artwork were evaluated. A significant difference in image quality scoring was found only for the lips and the tip of the nose, which appeared darker on non-corrected than on corrected PET images. In 33 patients, artefacts were seen on CT, and in 28 of these patients, artefacts were also seen on PET imaging. In eight patients without implants, artefacts were seen neither on CT nor on PET images. Direct comparison of PET(Ge68) and PET(CT) images showed a different appearance of artefacts in 3 of 17 patients. Malignant lesions were equally well visible using both transmission correction methods. Dental implants, non-removable bridgework etc. can cause artefacts in attenuation-corrected images using either a conventional 68Ge transmission source or the CT scan obtained with a combined PET/CT camera. We recommend that the non-attenuation-corrected PET images also be evaluated in patients undergoing PET of the head and neck.