Case Report: Durable therapy response to Osimertinib in rare EGFR Exon 18 mutated NSCLC.

Up to 20% of all non-small cell lung cancer patients harbor tumor specific driver mutations that are effectively treated with tyrosine kinase inhibitors. However, for the rare EGFR deletion-insertion mutation of exon 18, there is very little evidence regarding the effectiveness of tyrosine kinase inhibitors. A particular challenge for clinicians in applying tyrosine kinase inhibitors is not only diagnosing a mutation but also interpreting rare mutations with unclear therapeutic significance. Thus, we present the case of a 65-year-old Caucasian male lung adenocarcinoma patient with an EGFR Exon 18 p.Glu709_Thr710delinsAsp mutation of uncertain therapeutic relevance. This patient initially received two cycles of standard platinum-based chemotherapy without any therapeutic response. After administration of Osimertinib as second line therapy, the patient showed a lasting partial remission for 12 months. Therapy related toxicities were limited to mild thrombocytopenia, which ceased after dose reduction of Osimertinib. To our knowledge, this is the first report of effective treatment of this particular mutation with Osimertinib. Hence, we would like to discuss Osimertinib as a viable treatment option in EGFR Exon 18 p.Glu709_Thr710delinsAsp mutated lung adenocarcinoma.

Evaluation of diagnostic accuracy of dual-energy computed tomography in patients with chronic thromboembolic pulmonary hypertension compared to V/Q-SPECT and pulmonary angiogram.

Purpose: The relevance of dual-energy computed tomography (DECT) for the detection of chronic thromboembolic pulmonary hypertension (CTEPH) still lies behind V/Q-SPECT in current clinical guidelines. Therefore, our study aimed to assess the diagnostic accuracy of DECT compared to V/Q-SPECT with invasive pulmonary angiogram (PA) serving as the reference standard. Methods: A total of 28 patients (mean age 62.1 years ± 10.6SD; 18 women) with clinically suspected CTEPH were retrospectively included. All patients received DECT with the calculation of iodine maps, V/Q-SPECT, and PA. Results of DECT and V/Q-SPECT were compared, and the percent of agreement, concordance (utilizing Cohen's kappa), and accuracy (kappa2) to PA were calculated. Furthermore, radiation doses were analyzed and compared. Results: In total, 18 patients were diagnosed with CTEPH (mean age 62.4 years ± 11.0SD; 10 women) and 10 patients had other diseases. Compared to PA, accuracy and concordance for DECT were superior to V/Q-SPECT in all patients (88.9% vs. 81.3%; k = 0.764 vs. k = 0.607) and in CTEPH patients (82.4% vs. 70.1%; k = 0.694 vs. k = 0.560). Furthermore, the mean radiation dose was significantly lower for DECT vs. V/Q-SPECT (p = 0.0081). Conclusion: In our patient cohort, DECT is at least equivalent to V/Q-SPECT in diagnosing CTEPH and has the added advantage of significantly lower radiation doses in combination with simultaneous assessment of lung and heart morphology. Hence, DECT should be the subject of ongoing research, and if our results are further confirmed, it should be implemented in future diagnostic PH algorithms at least on par with V/Q-SPECT.

[Whipple's triad with high and low insulin levels]. / Whipple-Trias mit erhöhten und erniedrigten Insulinspiegeln.

A 69-year-old female patient and a 70-year-old male patient were admitted to hospital with recurrent, severe hypoglycemic episodes and a typical manifestation of Whipple's triad. In the female, elevated levels of insulin, C­peptide and pro-insulin together with pathological findings during a fasting test proved the presence of an insulinoma, which could be detected by Ga-68-DOTATOC-PET-CT in the pancreas. There was a very rare co-existence of a neuroendocrine Merkel cell carcinoma. In the male, levels of insulin and C­peptide were suppressed and a diagnosis of paraneoplastic hypoglycemia by IGF­2 secretion was made with increased glucose disposal in skeletal muscle proven by 18F­FDG-PET-CT.

Hodgkin Lymphoma after Disseminated Mycobacterium genavense Infection, Germany.

Mycobacterium genavense infection, a rare nontuberculous mycobacteria infection, occurs in heavily immunocompromised patients (i.e., those with advanced HIV disease, genetic disorders, or acquired immunologic disorders and those undergoing immunosuppressive therapy). We report a case of disseminated M. genavense infection preceding Hodgkin lymphoma in a patient without obvious risk factors for this infection.

Evaluation of Diagnostic Accuracy and Radiation Exposure of Dual-Energy Computed Tomography (DECT) in the Course of Chronic Thromboembolic Pulmonary Hypertension (CTEPH). / Evaluation der diagnostischen Genauigkeit und der Strahlendosis der Dual-Energy-Computertomografie (DECT) bei chronisch thromboembolischer pulmonaler Hypertonie (CTEPH).

PURPOSE: The purpose of this study was to assess the diagnostic accuracy of computed tomography pulmonary angiogram (CTPA) including dual energy and reconstruction of iodine maps for diagnosing CTEPH. This method for detecting embolisms and perfusion failures was compared with V/Q-SPECT. An additional purpose was to compare the applied radiation dose of both techniques. MATERIALS AND METHODS: 71 patients (49 women) with suspected CTEPH were included in this prospective study. The patients received a V/Q-SPECT and a dual-energy CTPA. Iodine maps were reconstructed from the data set. CTPA and the iodine maps were read by an experienced radiologist unaware of the clinical information as well as the results of the V/Q-SPECT. Results were compared to the V/Q-SPECT. DLP and the applied amount of radionuclides (MAA, Technegas) were obtained for comparison of radiation dose. RESULTS: For the diagnosis of CTEPH, the sensitivity of DECT was 1.000, specificity 0.966, PPV 0.867 and NPV 1.000, respectively. There was not a considerable difference in the x-ray exposure between the DECT examination and the V/Q-SPECT (1.892 mSv vs. 1.911 mSv; p = 0.6115). Both examination modalities were highly consistent regarding the classification of pathological segments (1177/1278 segments, 92,09 %, κ = 0,5938). CONCLUSION: This study presents the DECT, in combination with reconstructed iodine maps, as a potential alternative to the current imaging technique of first choice, V/Q-SPECT. For creating future prospective diagnostic algorithms, the implementation of DECT screening with iodine maps should be considered. KEY POINTS: · DECT correctly identified all CTEPH patients.. · There is substantial agreement between DECT and V/Q-SPECT in the classification of pathological segments.. · There is no significant difference in radiation exposure during DECT examination and V/Q-SPECT examination.. · Reduced radiation dose does not negatively impact image quality.. CITATION FORMAT: · Schüßler A, Richter M, Tello K et al. Evaluation der diagnostischen Genauigkeit und der Strahlendosis der Dual-Energy-Computertomografie (DECT) bei chronisch thromboembolischer pulmonaler Hypertonie (CTEPH). Fortschr Röntgenstr 2021; 193: 1318 - 1326.

Assessment of Waldeyer's ring in pediatric and adolescent Hodgkin lymphoma patients-Importance of multimodality imaging: Results from the EuroNet-PHL-C1 trial.

BACKGROUND: In the EuroNet Pediatric Hodgkin Lymphoma (EuroNet-PHL) trials, decision on Waldeyer's ring (WR) involvement is usually based on clinical assessment, that is, physical examination and/or nasopharyngoscopy. However, clinical assessment only evaluates mucosal surface and is prone to interobserver variability. Modern cross-sectional imaging technology may provide valuable information beyond mucosal surface, which may lead to a more accurate WR staging. PATIENTS, MATERIALS, AND METHODS: The EuroNet-PHL-C1 trial recruited 2102 patients, of which 1752 underwent central review including reference reading of their cross-sectional imaging data. In 14 of 1752 patients, WR was considered involved according to clinical assessment. In these 14 patients, the WR was re-assessed by applying an imaging-based algorithm considering information from 18 F-fluorodeoxyglucose positron emission tomography, contrast-enhanced computed tomography, and/or magnetic resonance imaging. For verification purposes, the imaging-based algorithm was applied to 100 consecutive patients whose WR was inconspicuous on clinical assessment. RESULTS: The imaging-based algorithm confirmed WR involvement only in four of the 14 patients. Of the remaining 10 patients, four had retropharyngeal lymph node involvement and six an inconspicuous WR. Applying the imaging-based algorithm to 100 consecutive patients with physiological appearance of their WR on clinical assessment, absence of WR involvement could be confirmed in 99. However, suspicion of WR involvement was raised in one patient. CONCLUSIONS: The imaging-based algorithm was feasible and easily applicable at initial staging of young patients with Hodgkin lymphoma. It increased the accuracy of WR staging, which may contribute to a more individualized treatment in the future.

Comparison of MRI and VQ-SPECT as a Screening Test for Patients With Suspected CTEPH: CHANGE-MRI Study Design and Rationale.

The diagnostic strategy for chronic thromboembolic pulmonary hypertension (CTEPH) is composed of two components required for a diagnosis of CTEPH: the presence of chronic pulmonary embolism and an elevated pulmonary artery pressure. The current guidelines require that ventilation-perfusion single-photon emission computed tomography (VQ-SPECT) is used for the first step diagnosis of chronic pulmonary embolism. However, VQ-SPECT exposes patients to ionizing radiation in a radiation sensitive population. The prospective, multicenter, comparative phase III diagnostic trial CTEPH diagnosis Europe - MRI (CHANGE-MRI, ClinicalTrials.gov identifier NCT02791282) aims to demonstrate whether functional lung MRI can serve as an equal rights alternative to VQ-SPECT in a diagnostic strategy for patients with suspected CTEPH. Positive findings are verified with catheter pulmonary angiography or computed tomography pulmonary angiography (gold standard). For comparing the imaging methods, a co-primary endpoint is used. (i) the proportion of patients with positive MRI in the group of patients who have a positive SPECT and gold standard diagnosis for chronic pulmonary embolism and (ii) the proportion of patients with positive MRI in the group of patients with negative SPECT and gold standard. The CHANGE-MRI trial will also investigate the performance of functional lung MRI without i.v. contrast agent as an index test and identify cardiac, hemodynamic, and pulmonary MRI-derived parameters to estimate pulmonary artery pressures and predict 6-12 month survival. Ultimately, this study will provide the necessary evidence for the discussion about changes in the recommendations on the diagnostic approach to CTEPH.

Intraindividual homogeneity of 18F-FDG PET/CT parameters in HPV-positive OPSCC.

OBJECTIVES: 18F-FDG PET/CT is widely used in clinical oncology. Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) represents an emerging disease that differs from HPV-negative OPSCC in clinical behavior and tumour biology. In these tumours, HPV-oncogenes might lead to distinct alterations in metabolic pathways. Therefore, we compared metabolic parameters using 18F-FDG PET/CT in HPV-positive and HPV-negative OPSCC in relation to histopathological findings. MATERIALS: Eighty-six patients with OPSCC received pre-therapeutic 18F-FDG PET/CT. Standardised uptake volume (SUV), total lesion glycolysis (TLG) and metabolic tumour volume (MTV) were analysed for the primary tumour. SUVmax was determined for neck lymph nodes. HPV-status was determined; overall survival rates (OS) were estimated. RESULTS: 32/86 patients (37.2%) had HPV-related OPSCC. Overall, PET-parameters in primary tumours of both groups did not differ significantly. Comparing early with locally advanced primary tumours, there was a significant increase in 18F-FDG uptake in HPV-negative patients (p<0.001). Positive nodes of HPV-related OPSCC showed significantly higher SUVmax values (p=0.039) compared to HPV-negative OPSCC. Strikingly, there was a higher intraindividual homogeneity of 18F-FDG uptake between primary and respective positive nodes in HPV-related primary OPSCC (p=0.001). SUV-max and -mean values did not correlate with OS in HPV-related OPSCC. CONCLUSION: The intraindividual homogeneity of 18F-FDG uptake in HPV-related OPSCC could reflect the more homogenously, HPV-triggered carcinogenesis compared to the mutation-driven carcinogenesis in the HPV-negative OPSCC with heterogenic 18F-FDG uptake.

A standardized technique of systematic mediastinal lymph node dissection by video-assisted thoracoscopic surgery (VATS) leads to a high rate of nodal upstaging in early-stage non-small cell lung cancer.

BACKGROUND: A substantial part of the oncologic surgical procedure in non-small cell lung cancer (NSCLC) is systematic lymph node dissection (sLND). However, controversies still exist regarding the quality of minimally invasive (video-assisted thoracoscopic surgery, VATS) sLND in oncologic resections. The rate of stage migration from clinical to pathological N-status has been discussed as one parameter for the quality of sLND. METHODS: Between March 2011 and May 2014, seventy-seven patients (62 male, 15 female) were scheduled for anatomical lung resection and sLND by VATS for clinical stage I (UICC 7th edition) NSCLC. Preoperative staging was performed by [18F]-fluorodesoxyglucose positron emission tomography with computed tomography (FDG-PET/CT). Patient data were retrospectively analyzed with regard to divergence in clinical and pathological N-factor. FDG-PET/CTs of patients with lymph node (LN) upstaging after VATS resections were blindly re-evaluated by an experienced radiologist. RESULTS: In FDG-PET/CT, preoperative tumor stage was cT1N0M0 in 41 (53.2%) and cT2aN0M0 in 28 (36.4%) patients. In six (7.8%) patients the primary tumor was not suspicious for malignancy, and in two (2.6%) patients the tumor was not evaluable due to prior wedge resection before FDG-PET/CT. Thirty-one (40.3%) left-sided and 46 (59.7%) right-sided pulmonary resections with sLND were performed; 19.57 ± 0.99 LNs were dissected. In 13 (16.9%) patients a nodal stage migration from preoperative clinical to postoperative pathological N-stage was observed [cN0 to pN1 in 9 (11.7%) and cN0 to pN2 in 4 (5.2%) cases]. In correlation to the clinical T-factor, the rate of N-factor upstaging for cT1 was 12.2% and for cT2a was 28.6%, respectively. In 50% of the patients with postoperative nodal staging shift, no changes were observed on re-evaluation of the preoperative FDG-PET/CT. CONCLUSION: In this series of clinical stage I NSCLC patients, the rate of nodal stage migration after sLND by VATS is higher than previously reported. Prospective randomized controlled trials are needed to prove the oncologic quality of a sLND by VATS versus standard open approach.

[77-year-old female with hyponatremia, pruritus and papulous exanthema]. / 77-jährige Patientin mit Hyponatriämie, Pruritus und papulösem Exanthem.

HISTORY AND CLINICAL FINDINGS: A 77 year old female patient was admitted for the evaluation of hyponatremia and a generalized papulous exanthema with severe pruritus. INVESTIGATIONS AND DIAGNOSIS: The syndrome of inappropriate antidiuretic hormone secretion (SIADH) could be diagnosed as cause for hyponatremia. Biopsy of a soft tissue tumor revealed a T-cell lymphoma with widespread skelettal dissemination. TREATMENT AND COURSE: Chemotherapy caused a rapid response and improvement of general well-being. SIADH could be controlled by the specific vasopressin-2-receptor antagonist tolvaptan. CONCLUSIONS: In this patient, both the papulous exanthema and the SIADH are regarded as T-cell-lymphoma-associated paraneoplastic syndromes.

Restrictive cardiomyopathy in inherited ATTR amyloidosis (TTR-Ser23Asn) in a patient of German-Italian extraction.

Amyloidosis occurs when certain soluble proteins are transformed into amyloid fibrils in the extracellular space. Most common are the light-chain amyloidoses; less common is the AA-amyloidosis, which follows chronic inflammatory diseases, and the amyloidoses of transthyretin (TTR) origin. We report on a women of Italian-German origin with the mutation TTR (Ser23Asn). Whole body scintigraphy using TC99m-DPD showed end stage hereditary amyloidosis caused by ATTR with predominant tracer retention in the myocardium. Myocardial biopsies revealed the presence of amyloid by Congo red staining. Further immunohistochemical analysis showed ATTR amyloidosis. DNA sequencing revealed a point mutation of the transthyretin gene leading to a single amino acid substitution. The only effective treatment in patients with manifest cardiac ATTR amyloidosis is combined heart and liver transplantation. Our patient was placed on a list for this procedure, but unfortunately she died during the standby procedure due to urosepsis.

Influence of dose rate on therapeutic success of radioiodine therapy of functional thyroid autonomy.

OBJECTIVE: To evaluate the effect of dose rate on the therapeutic success of radioiodine therapy (RIT) by retrospective analysis of two groups of patients with different dose rates during RIT. METHODS: The average dose rate until deposition of 50% of the total radiation dose achieved (the DL50 value) was calculated. Ninety patients with autonomy of the thyroid receiving radiation doses between 300 and 400 Gy were separated in groups with high DL50 values (the DL50 H group) and low DL50 values (the DL50L group). Before and 4 months after RIT free triiodothyronine (FT3), free thyroxine (FT4), basal thyroid stimulating hormone (TSHB), stimulated TSH (TSHS), thyroidal technetium uptake (TcTU), and the existence of focal abnormalities in thyroid scintigraphy were evaluated. RESULTS: The DL50 H and DL50L groups showed no differences before RIT in the parameters assessed as well as in total achieved dose and autonomous thyroid volume. After therapy a significant difference was found in TSHB with higher values in DL50 H (1.89+/-1.49 vs. 1.31+/-1.48 mU . l, P<0.05), FT4 showed a trend to lower values (13.8+/-4.0 vs. 16.1+/-6.2 pmol . l, P=0.09). CONCLUSION: The DL50 value has an influence on therapeutic success of RIT. This influence is only discrete and not likely to produce clinically relevant effects in the practical use of RIT.

Immunoscintigraphy of septic loosening of knee endoprosthesis: a retrospective evaluation of the antigranulocyte antibody BW 250/183.

Immunoscintigraphy with the use of the antigranulocyte antibody BW 250/183 is a reliable method for detecting infection, especially in septic loosening of hip prostheses, for which purpose quantitative interpretation of the time-activity course is employed. Therefore, we retrospectively studied whether similar results could be achieved in knee prostheses. We verified 28 scintigraphic examinations in 26 patients by histology. Scintigraphy was performed during an early (4-6 h post injection) and a late phase (23-25 h post injection). Infection was diagnosed when activity around the knee prosthesis increased by more than 10% compared with bone marrow. We found a sensitivity and a negative predictive value of 100%, a specificity of 80%, a positive predictive value of 81% and an accuracy of 89%. Specificity and accuracy are lower than in the evaluation of hip prostheses; however, in comparison to other scintigraphic modalities, scintigraphy with the antigranulocyte antibody BW 250/183 is superior in excluding infection and has better specificity and accuracy. Therefore, as in the case of hip prostheses, the described methodology appears to be the scintigraphic modality of choice for knee prostheses.

99mTc-DPD scintigraphy in transthyretin-related familial amyloidotic polyneuropathy.

Familial amyloidotic polyneuropathy (FAP) caused by amyloidogenic transthyretin (ATTR) mutations is the most common form of hereditary amyloidosis. We investigated the diagnostic value of the bone scanning agent technetium-99m 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) in this disease. Eight patients (four males, four females; age 54.4+/-8.3 years, range 43-67 years) with ATTR-FAP proven by immunohistochemistry and molecular analysis and a control group comprising ten oncological out-patients (five males, five females; age 53.4+/-8.5 years, range 34-66 years) without evidence of bony metastases were studied using 99mTc-DPD. Whole body tracer retention was 80.1%+/-10.3% (range 65.1%-94.8%) in FAP patients and 55.7%+/-8.1% (range 40.2%-66.7%) in controls at 3 h p.i. (P<0.001), and cardiac uptake was 7.3%+/-2.2% (range 4.2%-10.1%) in FAP patients and 3.1%+/-0.5% (range 2.3%-4.0%) in controls (P<0.001). The heart/whole body uptake ratio was 8.9%+/-1.7% (range 6.5%-11.0%) in FAP patients and 5.6%+/-0.5% (range 5.1%-6.8%) in controls (P<0.001). The three FAP patients with the highest cardiac tracer uptake had cardiomyopathy or arrhythmia. 99mTc-DPD scintigraphy is proposed as a simple and valuable diagnostic aid to evaluate the severity of the disease and the risk of concomitant heart problems.