Evaluation of erlotinib treatment response in non-small cell lung cancer using metabolic and anatomic criteria.

BACKGROUND: In this paper the clinical value of PET for early prediction of tumor response to erlotinib in patients with advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one prior chemotherapy regimen is evaluated. The aim was to compare the early metabolic treatment response using European Organization for Research and Treatment of Cancer (EORTC) 1999 recommendations and PET Response Criteria in Solid Tumors (PERCIST), and the standard treatment response using Response Evaluation Criteria in Solid Tumors (RECIST). METHODS: Twenty patients with stage IV NSCLC were enrolled prospectively. PET/CT studies were performed before, then 48 hours, and 45 days after the initiation of erlotinib treatment. The lesion with the highest uptake in each patient was evaluated according to EORTC 1999 recommendations, PERCIST and RECIST to assess metabolic and anatomic response. Response classifications were compared statistically using Wilcoxon signed-rank test. Disease-free survival (DFS) and overall survival (OS) were calculated by the Kaplan-Meier Test. RESULTS: At 48 hours, the Kaplan-Meier analysis showed that EORTC proved to be a significant prognostic factor for predicting DFS and OS. At 45 days, there was a significant difference in response evaluation between RECIST and metabolic classifications. RECIST and PERCIST were significant prognostic factors for predicting DFS and OS. EORTC was not able to discriminate responder from non-responder patients. CONCLUSIONS: This study shows that, according to the EORTC protocol, the PET exam is able to provide early identification of patients who benefit from Erlotinib treatment. Used at the end of therapy, PERCIST could be considered an appropriate metabolic evaluation method to discriminate responders from non-responders.

[68Ga]DOTATOC PET/CT Radiomics to Predict the Response in GEP-NETs Undergoing [177Lu]DOTATOC PRRT: The "Theragnomics" Concept.

Despite impressive results, almost 30% of NET do not respond to PRRT and no well-established criteria are suitable to predict response. Therefore, we assessed the predictive value of radiomics [68Ga]DOTATOC PET/CT images pre-PRRT in metastatic GEP NET. We retrospectively analyzed the predictive value of radiomics in 324 SSTR-2-positive lesions from 38 metastatic GEP-NET patients (nine G1, 27 G2, and two G3) who underwent restaging [68Ga]DOTATOC PET/CT before complete PRRT with [177Lu]DOTATOC. Clinical, laboratory, and radiological follow-up data were collected for at least six months after the last cycle. Through LifeX, we extracted 65 PET features for each lesion. Grading, PRRT number of cycles, and cumulative activity, pre- and post-PRRT CgA values were also considered as additional clinical features. [68Ga]DOTATOC PET/CT follow-up with the same scanner for each patient determined the disease status (progression vs. response in terms of stability/reduction/disappearance) for each lesion. All features (PET and clinical) were also correlated with follow-up data in a per-site analysis (liver, lymph nodes, and bone), and for features significantly associated with response, the Δradiomics for each lesion was assessed on follow-up [68Ga]DOTATOC PET/CT performed until nine months post-PRRT. A statistical system based on the point-biserial correlation and logistic regression analysis was used for the reduction and selection of the features. Discriminant analysis was used, instead, to obtain the predictive model using the k-fold strategy to split data into training and validation sets. From the reduction and selection process, HISTO_Skewness and HISTO_Kurtosis were able to predict response with an area under the receiver operating characteristics curve (AUC ROC), sensitivity, and specificity of 0.745, 80.6%, 67.2% and 0.722, 61.2%, 75.9%, respectively. Moreover, a combination of three features (HISTO_Skewness; HISTO_Kurtosis, and Grading) did not improve the AUC significantly with 0.744. SUVmax, however, could not predict the response to PRRT (p = 0.49, AUC 0.523). The presented preliminary "theragnomics" model proved to be superior to conventional quantitative parameters to predict the response of GEP-NET lesions in patients treated with complete [177Lu]DOTATOC PRRT, regardless of the lesion site.

Correlation between histological grade and positron emission tomography parameters in cervical carcinoma.

The aim of the present study was to evaluate the changes in cervical cancer glucose metabolism for different levels of cellular differentiation. The metabolic activity was measured by standardized uptake value (SUV), SUV normalized to lean body mass, metabolic tumor volume and total lesion glycolysis using fluorine-18 fluorodeoxyglucose positron emission tomography (PET). A correlation study of these values could be used to facilitate therapeutic choice and to improve clinical practice and outcome. This study considered 32 patients with diagnosed cervical cancers, at different International Federation of Gynecology and Obstetrics stages. Glucose metabolism was assessed by PET examination, and histological specimens were examined to determine their initial grade of differentiation. A correlation study of these values was evaluated. Histological examination showed that all cases were of squamous cell carcinoma. Regarding the differentiation of the tumor, 19 well- to moderately-differentiated tumors and 13 poorly-differentiated tumors were determined. Negative findings for correlations between metabolic parameters and initial grade of histological differentiation were found, and considering that histological grade has been shown to have no consistent prognostic value in cervical cancer treatment, PET imaging could play a significant role in cervical cancer prognosis.

Timing of examination affects reliability of 99mTc-methoxyisobutylisonitrile SPECT in distinguishing neoplastic from nonneoplastic brain hematomas.

UNLABELLED: 99mTc-methoxyisobutylisonitrile (MIBI) SPECT has been reported to be 100% sensitive and specific in the early differential diagnosis between neoplastic and nonneoplastic intraparenchymal cerebral hemorrhage (ICH), because nonneoplastic ICH does not show 99mTc-MIBI accumulation on SPECT examinations performed within 48 h from the onset of clinical symptoms. The aims of this study were to investigate the behavior of nonneoplastic ICH on more delayed 99mTc-MIBI SPECT examinations and to determine how the timing of examination affects the reliability of 99mTc-MIBI SPECT in differentiating neoplastic from nonneoplastic ICH. METHODS: We prospectively enrolled 32 patients with acute neurologic deterioration caused by nontraumatic ICH. Patients were randomly allocated to 4 groups of 8 patients each. Patients in the first, second, third, and fourth groups underwent 99mTc-MIBI SPECT 2, 5, 10, and 30 d, respectively, after the onset of clinical deterioration. Furthermore, patients in the first group underwent a second (99m)Tc-MIBI SPECT examination at 30 d. 99mTc-MIBI SPECT studies were visually and semiquantitatively evaluated. Patients were followed up to confirm the nonneoplastic etiology of the ICH. RESULTS: Two of the 32 studied patients, 1 in the second and 1 in the fourth group, were excluded because the ICH turned out to be related to a neoplastic lesion. Visual analysis showed no 99mTc-MIBI uptake in any patient studied at 2 d, whereas increased radiotracer uptake was found in 1 (14%) of 7, 5 (62.5%) of 8, and 5 (71%) of 7 patients studied 5, 10, and 30 d, respectively, after clinical deterioration. Moreover, with the semiquantitative analysis, a statistically significant difference was found among 99mTc-MIBI indices in the 4 groups (P = 0.0011). All patients in group 1 showed a significant 99mTc-MIBI accumulation when studied at 30 d. CONCLUSION: Nonneoplastic ICH, showing no 99mTc-MIBI uptake within 2 d, can show 99mTc-MIBI accumulation on more delayed imaging. 99mTc-MIBI SPECT can clearly differentiate between neoplastic and nonneoplastic ICH only during the acute phase. Our findings suggest that examination be performed early after the onset of symptoms and certainly within 5 d.

[PET with C-methionine and hyperparathyroidism].

Scintigraphy 99mTc-sestamibi, in association ultrasound of the neck, is currently the technique of choice for the location of parathyroid adenomas in patients with hyperparathyroidism then undergo parathyroidectomy. After surgery, from 2% to 7% of patients continues to have a persistence of the disease. In this case, the sensitivity of scintigraphy with MIBI in locating ectopic parathyroid glands is limited and varies from 30% to 80%. Thanks to the introduction of a new method radiological, PET with 11C-methionine, it is now possible to detect the possible presence of parathyroid adenomas in patients with MIBI scintigraphy been examined and is also useful for false positives. PET with 11C-methionine is a diagnostic accurate in locating the parathyroid adenomas of the neck with a sensitivity of 91%, allowing you to run parathyroidectomy focused with a reduced invasiveness of surgery, with reduction of postoperative pain and better results aesthetic. In addition, a method is clinically useful in patients with secondary hyperparathyroidism and tertiary. The limits of this promising method are the poor availability of the tracer, the fact that it is executed in only four centers in Italy and the high cost. We present the cases of two patients who are diagnosed with hyperparathyroidism. They are submitted in the first instance to MIBI parathyroid scintigraphy parathyroidectomy and after removal of pathological glands. Persisting high values of PTH, patients are executed before a new scintigraphy with MIBI which is however negative and then a PET with 11C-methionine which shows accumulation of tracer in a different place not detected by scintigraphy.