Hyperprogression after nivolumab for melanoma: A case report.

BACKGROUND: Nivolumab is an immune checkpoint inhibitor that selectively blocks the programmed cell death-1. Nowadays, immune checkpoint inhibitors such as nivolumab are used in the treatment of many different types of cancer. Treatment responses of these agents may be different from standard chemotherapy, and hyperprogression is a new entity that occurs with immune checkpoint inhibitors. We present a case of hyperprogressive disease precipitated by anti-programmed cell death-1 immunotherapy. CASE REPORT: A 25-year-old woman was treated with ipilimumab, dabrafenib plus trametinib, and nivolumab, respectively, for stage IV melanoma. Palliative whole brain radiotherapy was completed due to brain metastases before the administration of nivolumab. After the fourth cycle of nivolumab, the patient's general condition deteriorated and control positron emission tomography/computed tomography confirmed hyperprogression. Also, brain magnetic resonance imaging indicated the hyperprogression of the metastatic lesions. MANAGEMENT AND OUTCOME: After brain magnetic resonance imaging and positron emission tomography/computed tomography showed the hyperprogressive disease, nivolumab was discontinued. Cisplatin and dacarbazine were initiated for melanoma. DISCUSSION: Anti-programmed cell death-1 immunotherapy is effective in cancers. These agents can precipitate hyperprogressive disease. As the use of anti-programmed cell death-1 agents is expected to rise, physicians should be educated about the potential possibility of hyperprogression during the immunotherapy.

Complete response after ceritinib treatment in non-small cell lung cancer in an elderly patient.

INTRODUCTION: Ceritinib is a selective second-generation ALK inhibitor that is highly sensitive to echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) molecule. CASE REPORT: In this paper, we report a 68-year-old female that was diagnosed with stage 4 ALK-positive non-small cell lung cancer (NSCLC).Management and outcome: She was treated with crizotinib first-line, cisplatin and gemcitabine as second-line. And for third-line, ceritinib was started. She had complete response over 3.5 years under ceritinib treatment. And she is still receiving ceritinib with no adverse event. DISCUSSION: Cases achieving complete response with ceritinib treatment are rare. In this paper, we aimed to emphasize the complete response in stage 4 NSCLC in an elderly patient.

The clinical and biochemical presentation of vitamin D deficiency and insufficiency in children and adolescents.

AIM: To evaluate the clinical and biochemical findings of the children and adolescents with vitamin D deficiency and insufficiency in order to determine the clinical and biochemical presentation differences between age groups. METHODS: This retrospective study included a review of medical reports of 543 patients (aged between 1-17 years) who were referred to our hospital between October 2011 and May 2012 with symptoms related to vitamin D deficiency or insufficiency. The patients were divided into four groups by age: 1-3 years (Group 1), 4-6 years (Group 2), 7-11 years (Group 3) and 12-17 years (Group 4). Patients diagnosed with vitamin D deficiency or insufficiency were evaluated as to their clinical and biochemical findings. RESULTS: Gender distribution were not statistically different between the four groups. The mean ages of Groups 1-4 were 1.9±0.7, 5.1±0.9, 8.9±1.3, 13.1±1.1, respectively. Major complaints on admission were muscle weakness (91%), low weight gain (failure to thrive) (89%), head deformity (frontal bossing) (35.6%), bone deformity (enlargement of wrist and ankles) (29.7%) for Group 1. Muscle weakness (76%) and low weight gain (failure to thrive) (68%) for Group 2. Leg and chest pain were the major symptoms in Group 3 (57% and 28%, respectively) and in Group 4 (26% and 55%, respectively) as well as high rates of obesity (31% and 63%). The biochemical findings of vitamin D deficiency mostly appeared in the first group who developed vitamin D deficiency due to the lack of vitamin D supplementation. However, in older children, the majority of the patients had low 25 hydroxyvitamin D (25 OHD) values without evidence of biochemical findings of osteomalacia. CONCLUSION: Depending on the degree of deficiency and insufficiency, and the age of the patients, the clinical and biochemical findings varied widely. Children under the age of 3 who either never received vitamin D supplementation or who had been receiving supplementation that was stopped too early were at a greater risk for developing clinically and biochemically proved vitamin D deficiency. In older children, low vitamin D levels mostly resulted in subtle complaints without abnormal biochemical findings.

The relationship between tumor mean standard uptake value (SUVmax) in preoperative PET/computed tomography and prognostic risk groups in endometrial cancer.

OBJECTIVE: Our aim in this study was to determine the relationship between tumor mean standard uptake value (SUVmax) value in preoperative PET/computed tomography (CT) and prognostic risk groups in cases with endometrial cancer. METHODS: A total of 368 patients operated on for endometrial cancer were evaluated in the study. The SUVmax value of endometrial primary tumor of the patients screened within 30 days of operation, was compared with prognostic parameters and risk groups. P value <0.05 was considered significant for all tests. RESULTS: A statistically significant relationship was found between the mean SUVmax value and risk groups ( P < 0.001), grade ( P < 0.001), stage ( P < 0.001), myometrial invasion of the tumor ( P < 0.001), cervical involvement ( P = 0.002), lymphovascular space invasion (LVSI) ( P < 0.001), lymph node metastasis ( P < 0.001), tumor size ( P < 0.001), lymph node involvement in PET/CT ( P < 0.001). There was no significant relationship found between the histologic type of tumor and the mean SUVmax value ( P = 0.113). Cutoff SUVmax value for endometrial cancer tumor tissue, which will be used to determine the possible lymph node metastasis, was accepted as 19 as a result of the ROC analysis. The risk of lymph node metastasis was found 4.74 times (confidence interval, 2.510-8.977) higher in patients with SUVmax value above cutoff 19 ( P < 0.001). Considering risk groups, it was observed that patients with mean SUVmax value above 19 were in intermediate-high and high risk group, 2.3 times more than those in low and intermediate risk group ( P < 0.001). As a result of logistic regression analysis, in determining intermediate-high and high-risk groups, histological type ( P < 0.001), myometrial invasion ( P = 0.003), cervical invasion (CI) ( P < 0.001), grade ( P = 0.018) and SUVmax value ( P = 0.028) had statistically significant importance. CONCLUSION: The higher the mean SUVmax value in the endometrial cancer tumor tissue in preoperative PET/CT in patients with endometrial cancer, the higher the risk group of the patients.

Breast cancer to thyroid gland: An unconventional metastatic site.

Thyroid gland blood supply is rich but it is not an open area for metastasis. Only 1%-3% of the neoplastic lesions seen in the thyroid are of extrathyroidal origin. Thyroid, lung, bone, lymph node metastasis were detected at the time of diagnosis in a 78-year-old woman with metastatic breast cancer. Control imaging was performed 3 months after hormone therapy was started. All lesions were regressed except thyroid lesion and neck lymph. Tru-cut biopsy was performed to the lesion in the thyroid. The result is consistent with breast cancer metastasis. With this breast cancer metastasis to thyroid case, we want to emphasize the differential diagnosis of neoplastic lesions in the thyroid is important in those diagnosed with malignancy. If there is clinical suspicion after a nondiagnostic thyroid sampling, repeated biopsies should be performed.

The impact of different computational assumptions in 131 I dosimetry for hyperthyroidism therapy.

PURPOSE: The goal of the current study was to investigate the impact of different computational models on 131 I dosimetry prior to hyperthyroidism therapy. It was also aimed to highlight an accurate and cost-effective method for routine dosimetry of graves and toxic adenoma patients. METHODS: A cohort of 45 patients was recruited in the current study with Graves (n = 30) and Toxic Adenoma (n = 15) diseases. The eligibility criterion was determined using the patients' blood test, 99m Tc- pertechnetate scintigraphy, and ultrasound scan. A properly calibrated thyroid probe equipped with sodium iodide crystal [NaI(Tl)] was used to obtain the uptake measurements at 2, 24, 48, 72, and 96 h following administration of 0.27-0.73 MBq 131 I tracer. The absorbed radiation dose of the thyroid gland/nodule was calculated by three different methods. The calculation models were based on the time-integrated activity (recommended by MIRD), effective half-life (recommended by EANM), and ellipsoidal-shape assumption. RESULTS: The mean effective half-life was 138 ± 41 h and 110 ± 48 h in Graves and Toxic Adenoma patients, respectively. The mean residence time was 125 ± 5 h in Graves patients, while it was 93 ± 55 h in Toxic Adenoma. The amount of 131 I activity required to deliver 200 Gy to the thyroid gland in Graves patients was calculated as 436 ± 381 MBq, 426 ± 370 MBq, and 488 ± 455 MBq according to MIRD, EANM, and ellipsoidal-shape model, respectively. However, the activity required to impart 300 Gy in the toxic nodules was computed as 622 ± 332 MBq by MIRD, 907 ± 588 MBq by EANM, and 1060 ± 639 MBq by the ellipsoidal-shape model. Overall, no significant difference was found between the MIRD and both of the EANM and ellipsoidal-shape models in the Graves patients (R2  = 0.99, P > 0.05). In contrast, less agreement (R2  = 0.86) was shown between EANM and MIRD in Toxic Adenoma patients with no statistically significant difference (P > 0.05), while the difference was significant (Pvalue  < 0.05) between the MIRD and the ellipsoidal-shape model with moderate association (R2  = 0.66). CONCLUSION: It was deduced that the effective half-life-based model (EANM model) is a successful and affordable method for performing dosimetry in Graves patients. While, unit density sphere model sounds the most appropriate approach to be used in Toxic Adenoma dosimetry. However, using the ellipsoidal-shape assumption in the thyroid gland/or nodule dose calculation leads to redundantly larger activity administration.

Comparison of PERCIST and RECIST criteria for evaluation of therapy response after yttrium-90 microsphere therapy in patients with hepatocellular carcinoma and those with metastatic colorectal carcinoma.

OBJECTIVE: Yttrium-90 (Y) microsphere therapy has been increasingly used to treat hepatocellular carcinoma (HCC) and liver metastasis of colorectal cancer (mCRC). This study aims to compare two different criterias used for therapy response evaluation following Y therapy within the same group of patients. PATIENTS AND METHODS: A total of 21 patients with HCC and 19 patients with mCRC were included in this study, with 36 and 42 liver lesions, respectively. The lesions were evaluated before and after therapy by CT or MRI and fluorine-18 fluorodeoxyglucose (F-FDG) PET/CT. Several metabolic parameters were analyzed including maximum and mean standardized uptake values, peak standardized uptake value, metabolic tumor volume (MTV), and total lesion glycolysis. Tumor volume was determined using CT or MRI images for all lesions, and the applied activity was estimated to deliver 120±20 Gy for the treated lobe. Six weeks after Y microsphere therapy, F-FDG PET/CT scan was performed to evaluate tumor response using PERCIST and RECIST criteria. Overall survival was calculated using Kaplan-Meier method. RESULTS: A total of 78 liver lesions were treated without any major complication. The mean tumor volumes of HCC lesions calculated by CT or MRI before and after therapy were 84.38 and 86.62 cm, respectively. The average MTV of these lesions on PET images was calculated as 68.142 mm before therapy and 56.945 mm after treatment. In patients with mCRC, the mean tumor volume was 52.32 cm before therapy and 54.52 cm after therapy. The average MTV was calculated as 41.720 mm before and 44.967 mm after therapy for the same patient group. Response Evaluation Criteria In Solid Tumors (RECIST) and PET Response Criteria In Solid Tumors incompatibility was seen in seven of 36 lesions in HCC-diagnosed patients and seven of 42 lesions in patients with mCRC. The mean overall survival was calculated as 13.09 months in patients with HCC and 10.6 months in patients with mCRC. CONCLUSION: Y therapy response can be evaluated by both RECIST and European Organization for Research and Treatment of Cancer criteria. However, RECIST and European Organization for Research and Treatment of Cancer incompatibility can be seen. The anatomic methods for evaluating HCC response is relatively more accurate, whereas the metabolic parameters guided by PET/CT scan showed greater importance in response to evaluation of liver mCRC.

Normal distribution pattern and physiological variants of 68Ga-PSMA-11 PET/CT imaging.

PURPOSE: Ga-PSMA-11 is a novel PET tracer suggested to be used for imaging of advanced prostate cancer. In this study, we aimed to present a detailed biodistribution of Ga-PSMA-11, including physiological and benign variants of prostate-specific membrane antigen (PSMA) imaging. MATERIALS AND METHODS: We carried out a retrospective analysis of 40 patients who underwent PSMA PET/computed tomography (CT) imaging and who had no evidence of residual or metastatic disease on the scans. In addition, 16 patients who underwent PSMA PET/CT imaging with any indication other than prostate cancer were included in the study to evaluate physiological uptake in the normal prostate gland. The median, minimum-maximum, and mean standardized uptake value (SUV) values were calculated for visceral organs, bone marrow and lymph nodes, and mucosal areas. Any physiological variants or benign lesions with Ga-PSMA-11 were also noted. RESULTS: Ga-PSMA-11 uptake was noted in the kidneys, parotid and submandibular glands, duodenum, small intestines, spleen, liver, and lacrimal glands, and mucosal uptake in the nasopharynx, vocal cords, pancreas, stomach, mediastinal blood pool, thyroid gland, adrenal gland, rectum, vertebral bone marrow, and testes. Celiac ganglia showed slight Ga-PSMA-11 uptake in 24 of 40 patients without the presence of any other pathologic lymph nodes in abdominal and pelvic areas. Variable uptake of Ga-PSMA-11 was observed in calcified choroid plexus, a thyroid nodule, an adrenal nodule, axillary lymph nodes and celiac ganglia, occasional osteophytes, and gallbladder. The patient group with PSMA PET/CT for indications other than prostate cancer (n=16) showed a slight radiotracer uptake in normal prostate gland (SUVmax: 5.5±1.6, range: 3.5-8.3). CONCLUSION: This study shows normal distribution pattern, range of SUVs, and physiological variants of Ga-PSMA-11. In addition, several potential pitfalls were documented to prevent misinterpretations of the scan.