Diagnostic value of sentinel lymph node scintigraphy and 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography in the detection of metastatic lymph nodes in patients with early-stage cervical cancer.

Cervical cancer is staged clinically using the International Federation of Gynaecology and Obstetrics staging system. Although lymph node status does not form part of the staging, it has important prognostic and potential therapeutic implications. The aim of the study was to evaluate the role of sentinel lymph node (SLN) scintigraphy and 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in detecting lymph node metastases in patients with early-stage cervical cancer. Thirty-six patients with early-stage cervical cancer underwent SLN detection during primary operation. Of the 36 patients, 28 patients underwent 18F-FDG PET/CT before surgery. The 18F-FDG PET/CT images were analyzed with the histopathological findings as the reference standard. The diagnostic performance of 18F-FDG PET/CT in the detection of nodal disease was reported in terms of accuracy value. The SLN detection rate was the highest (91.7%) using the combined method (lymphoscintigraphy, intraoperative gamma probe, and blue dye). Seven of the thirty-six patients had lymph node involvement (19.4%), of which five had preoperative 18F-FDG PET/CT imaging. On overall patient-based analysis, the sensitivity, specificity, positive predictive value, negative predictive value (NPV), and accuracy of 18F-FDG PET/CT were 40.0%, 78.3%, 28.6%, 85.7%, and 71.4%, respectively. The combination of radiolabeled nanocolloid with blue dye is safe and reliable and allows successful detection of SLNs in patients with early-stage cervical cancer in a population with high prevalence of human immunodeficiency virus. The specificity and NPV of 18F-FDG PET/CT are high and can be used in conjunction with SLN biopsy.

Predictors of Overall and Disease-Free Survival in Metastatic Castration-Resistant Prostate Cancer Patients Receiving 225Ac-PSMA-617 Radioligand Therapy.

Metastatic prostate carcinoma overexpresses prostate-specific membrane antigen (PSMA), making this antigen a suitable target for radioligand therapy of the disease. Here we report on our experience with a series of 73 castration-resistant prostate carcinoma patients treated with 225Ac-PSMA-617, identifying variables predictive for overall survival (OS) and progression-free survival (PFS) after 225Ac-PSMA-617 treatment. Methods:225Ac-PSMA-617 was administered to patients who had metastatic castration-resistant prostate carcinoma and who had exhausted available therapy options for their disease. Full blood count, glomerular filtration rate, and liver function test were obtained at baseline and on follow-up for evaluation of toxicity. 68Ga-PSMA PET/CT was obtained at baseline, before every treatment cycle, and on follow-up for selection of patients for treatment, to determine the activity of the treatment agent to be administered, and for response assessment. Serial prostate-specific antigen (PSA) was obtained for PSA response assessment. Results: Seventy-three men (mean age, 69 y; range, 45-85 y) with metastatic castration-resistant prostate carcinoma were treated with 210 cycles of 225Ac-PSMA-617. In 70% of patients, a PSA decline of greater than or equal to 50% was obtained; 82% of patients had any PSA decline. In 29% of patients, all lesions on 68Ga-PSMA PET resolved in response to treatment. During follow-up, 23 patients experienced disease progression, whereas 13 patients died from their disease. The estimated median PFS and OS were 15.2 mo (95% CI, 13.1-17.4) and 18 mo (95% CI, 16.2-19.9), respectively. In univariate analyses, factors such as baseline PSA, any PSA decline, PSA decline of greater than or equal to 50%, prior chemotherapy, prior radiation therapy, and baseline hemoglobin level were associated with longer PFS and OS (all Ps < 0.05). In multivariate analyses, there was a negative association between prior 177Lu-PSMA therapy and PFS, and a positive association between PSA decline of greater or equal to 50% and PFS. Only a PSA decline of greater than or equal to 50% remained significantly associated with OS on multivariate analyses. Xerostomia was seen in 85% of patients but was not severe enough to warrant discontinuing treatment. Anemia was seen in 27 patients; no patients had grade IV bone marrow toxicity. Renal failure of grade III or IV was seen in 5 patients with baseline renal impairment. Conclusion: In this study, a PSA decline of greater than or equal to 50% after treatment with 225Ac-PSMA-617 was proven by multivariate analyses to be significantly associated with OS and PFS. Furthermore, previous 177Lu-PSMA treatment was negatively associated with PFS in both univariate and multivariate analyses.

Correction to: 225Ac-PSMA-617 in chemotherapy-naive patients with advanced prostate cancer: a pilot study.

The author of this article wanted to change the ethical approval statement of the originally published version of this article. Correct statement is indicated below.

Fluorodeoxyglucose Positron Emission Tomography integrated with computed tomography in carcinoma of the cervix: Its impact on accurate staging and the predictive role of its metabolic parameters.

OBJECTIVES: To determine the impact of FDG-PET/CT in the initial staging of cervical cancer among women with and without HIV and to determine the abilities of FDG-PET/CT metabolic parameters in predicting the presence of distant metastasis. METHODS: We reviewed the FDG-PET/CT images of women with FIGO stage IB2 to IVA carcinoma of the cervix. We compared the FIGO stage before and after FDG-PET/CT. Maximum and mean standardized uptake values (SUVmax and SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of the primary lesion were determined. We compared these parameters between the HIV-infected and uninfected woman and also determined their abilities to predict the presence of distant metastasis. RESULTS: 126 women, mean age 48.05 ± 11.80 years were studied. Seventy-three patients were HIV-infected. The disease was upstaged in 65 patients, 32 of which were upstaged to stage IVB. HIV-infected women were younger (43.36 ± 8.03 years versus 54.51 ± 13.12, p<0.001) and had more advanced disease (p = 0.022) compared with HIV-uninfected. In a univariate logistic regression adjusted for the FIGO stage of the disease, there were significant associations between MTV and TLG of the primary tumor and distant metastasis. SUVmax, SUVmean, MTV and TLG performed well in predicting the presence of distant metastasis with areas under the curves (AUCs) of 0.63, 0.66, 0.80 and 0.77 respectively. These performances improved after adjustment for the FIGO stage of the disease with AUCs of 0.80, 0.79, 0.84 and 0.82 for SUVmax, SUVmean, MTV and TLG respectively. CONCLUSION: Inclusion of 18F-FDG-PET/CT in the pre-therapy assessment of cervical cancer improves the accuracy of staging in about half of the patients. The metabolic parameters of the primary tumor perform well in predicting the presence of distant metastases.

225Ac-PSMA-617 in chemotherapy-naive patients with advanced prostate cancer: a pilot study.

BACKGROUND: A remarkable therapeutic efficacy has been demonstrated with 225Ac-prostate-specific membrane antigen (PSMA)-617 in heavily pre-treated metastatic castration-resistant prostate cancer (mCRPC) patients. We report our experience with 225Ac-PSMA-617 therapy in chemotherapy-naïve patients with advanced metastatic prostate carcinoma. METHODS: Seventeen patients with advanced prostate cancer were selected for treatment with 225Ac-PSMA-617 in 2-month intervals, with initial activity of 8 MBq, then de-escalation to 7 MBq, 6 MBq or 4 MBq in cases of good response. In one patient, activity was escalated to 13 MBq in the third cycle. Fourteen patients had three treatment cycles administered, while in three patients treatment was discontinued after two cycles due to good response. Six out of 17 patients received additional treatments after the third cycle. Prostate-specific antigen (PSA) was measured every 4 weeks for PSA response assessment. 68Ga-PSMA-PET/CT was used for functional response assessment before each subsequent treatment cycle. Serial full blood count, renal function test, and liver function were obtained to determine treatment-related side effects. RESULTS: Good antitumor activity assessed by serum PSA level and 68Ga-PSMA-PET/CT was seen in 16/17 patients. In 14/17 patients, PSA decline ≥90% was seen after treatment, including seven patients with undetectable serum PSA following two (2/7) or three cycles (5/7) cycles of 225Ac-PSMA-617. Fifteen of 17 patients had a > 50% decline in lesions avidity for tracer on 68Ga-PSMA-PET/CT including 11 patients with complete resolution (PET-negative and either stable sclerosis on CT for bone or resolution of lymph node metastases) of all metastatic lesions. Grade 1/2 xerostomia was seen in all patients, and none was severe enough to lead to discontinuation of treatment. One patient had with extensive bone marrow metastases and a background anemia developed a grade 3 anemia while another patient with solitary kidney and pre-treatment grade 3 renal failure developed grade 4 renal toxicity following treatment. The group presented with significant palliation of bone pain and reduced toxicity to salivary glands due to de-escalation. CONCLUSIONS: 225Ac-PSMA-617 RLT of chemotherapy-naïve patients with advanced metastatic prostate carcinoma led to a ≥ 90% decline in serum PSA in 82% of patients including 41% of patients with undetectable serum PSA who remained in remission 12 months after therapy. The remarkable therapeutic efficacy reported in this study could be achieved with reduced toxicity to salivary glands due to de-escalation of administered activities in subsequent treatment cycles. This necessitates further exploration for informing clinical practice and clinical trial design.

18F-FDG-PET metabolic metrics and International Prognostic Score for risk assessment in HIV-infected patients with Hodgkin lymphoma.

OBJECTIVES: Baseline metabolic metrics on fluorine-18-fluorodeoxyglucose PET (F-FDG PET) have prognostic value in Hodgkin lymphoma. International Prognostic Score (IPS) is used in the risk stratification of Hodgkin lymphoma. We compared the metabolic indices in HIV-infected and the IPS in HIV-infected and uninfected patients with Hodgkin lymphoma. PATIENTS AND METHODS: We retrospectively reviewed the data of HIV-infected and HIV-uninfected patients with classic Hodgkin lymphoma who had F-FDG PET for staging and compared the maximum standardized uptake value, mean standardized uptake value, metabolic tumor volume, and total lesion glycolysis between the two groups. We also compared the IPS and other prognostic indicators and correlated them with the metabolic indices in the two groups. RESULTS: We studied 160 patients, which included 57 patients who were infected with HIV. The mean age was 33.84±11.88 years, with 38% (n=61) being female. The median cluster of differentiation 4 count and HIV viral load were 259 cells/mm and 4837.50 copies/ml, respectively. No significant difference in maximum standardized uptake value, mean standardized uptake value, metabolic tumor volume, and total lesion glycolysis between the two groups was found. Among the seven parameters of the IPS, only male sex (HIV-uninfected group higher, P=0.005) and serum albumin less than 4 g/dl were significantly different. The other parameters were not significantly different between the two groups. Other prognostic indicators including bulky disease, extranodal involvement, and the number of nodal groups involved were not significantly different between the two groups. CONCLUSION: There was no significant difference in F-FDG metabolic parameters, IPS, and other risk indicators between HIV-infected and HIV-uninfected patients with Hodgkin lymphoma.

Use of a Sentinel Lymph Node Biopsy Algorithm in a South African Population of Patients With Cervical Cancer and High Prevalence of Human Immunodeficiency Virus Infection.

OBJECTIVES: Cervical cancer is common in resource-poor settings with high prevalence of tuberculosis, pelvic inflammatory disease, and human immunodeficiency virus (HIV) infection. There are no data regarding the sentinel lymph node (SLN) algorithm in these high-risk cancer populations. Our objectives were to establish the sensitivity, specificity, positive predictive value, and negative predictive value of the SLN algorithm in cervical cancer and to compare the detection rate of indocyanine green (ICG) versus blue dye versus technetium Tc 99m nanocolloid (Tc). METHODS: This prospective study was conducted at the University of Pretoria. Tc-nanocolloid tracer, ICG dye, and methylene blue (MB) were used to detect SLNs. Pathological ultrastaging was performed on hematoxylin-eosin- negative nodes. RESULTS: Results of 72 women were analyzed. The mean age was 47.2 years, 5.5% had a history of tuberculosis, 18.1% had pelvic inflammatory disease, and 65.3% were HIV positive. The SLN detection rate was 65.3%. Detection rate of MB was 56.9%; Tc, 69.4%; ICG, 87.5%; and the combination of MB and Tc, 91.7%. Pelvic nodal metastases occurred in 26.4%. The sensitivity, specificity, negative predictive value, and positive predictive value of SLN biopsy were 85.7%, 100%, 100%, and 98.33%, respectively. The false-negative rate was 14.3%, and it was 0% if the algorithm was applied. CONCLUSIONS: The SLN algorithm is a feasible option for use in cervical cancer women with a high prevalence of HIV infection. The detection rate is generally lower, but in select subgroups of women, it was comparable to that reported elsewhere. This is the first report of the use of SLN biopsy in a substantial group of HIV-infected women.

Intraindividual Comparison of 18F-PSMA-1007 and 18F-DCFPyL PET/CT in the Prospective Evaluation of Patients with Newly Diagnosed Prostate Carcinoma: A Pilot Study.

The introduction of 18F-labeled prostate-specific membrane antigen (PSMA)-targeted PET/CT tracers, first 18F-DCFPyL (2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) and more recently 18F-PSMA-1007 (((3S,10S,14S)-1-(4-(((S)-4-carboxy-2-((S)-4-carboxy-2-(6-18F-fluoronicotinamido)butanamido)butanamido)methyl)phenyl)-3-(naphthalen-2-ylmethyl)-1,4,12-trioxo-2,5,11,13-tetraazahexadecane-10,14,16-tricarboxylic acid)), have demonstrated promising results for the diagnostic workup of prostate cancer. This clinical study presents an intraindividual comparison to evaluate tracer-specific characteristics of 18F-DCFPyL versus 18F-PSMA-1007. Methods: Twelve prostate cancer patients, drug-naïve or before surgery, received similar activities of about 250 MBq of 18F-DCFPyL and 18F-PSMA-1007 48 h apart and were imaged 2 h after injection on the same PET/CT scanner using the same reconstruction algorithm. Normal-organ biodistribution and tumor uptake were quantified using SUVmaxResults: PSMA-positive lesions were detected in 12 of 12 prostate cancer patients. Both tracers, 18F-DCFPyL and 18F-PSMA-1007, detected the same lesions. No statistical significance could be observed when comparing the SUVmax of 18F-DCFPyL and 18F-PSMA-1007 for local tumor, lymph node metastases, and bone metastases. With regard to normal organs, 18F-DCFPyL had statistically significant higher uptake in kidneys, urinary bladder, and lacrimal gland. Vice versa, significantly higher uptake of 18F-PSMA-1007 in muscle, submandibular and sublingual gland, spleen, pancreas, liver, and gallbladder was observed. Conclusion: Excellent imaging quality was achieved with both 18F-DCFPyL and 18F-PSMA-1007, resulting in identical clinical findings for the evaluated routine situations. Nonurinary excretion of 18F-PSMA-1007 might present some advantage with regard to delineation of local recurrence or pelvic lymph node metastasis in selected patients; the lower hepatic background might favor 18F-DCFPyL in late stages, when rare cases of liver metastases can occur.

Salivary Gland Activity Obscures Mandibular Metastasis of Prostate Carcinoma on 68Ga-Prostate-Specific Membrane Antigen PET.

We report a case of a 65-year-old man with prostate cancer; his treatment history included radical prostatectomy followed by radiation therapy and subsequent androgen deprivation therapy for more than 5 years. He currently presented with a history of rising prostate-specific antigen and complained of jaw aches. Ga-prostate-specific membrane antigen PET/CT study performed for suspected biochemical recurrence demonstrated vertebral lesions and lesion in his jaw. Subsequent biopsy of jaw lesion demonstrated prostate cancer metastases.

Burkitt lymphoma and cavernous sinus syndrome with breast uptake on 18F-FDG-PET/CT: A case report.

RATIONALE: Burkitt lymphoma (BL) is a type of non-Hodgkin lymphoma that arises in the B-cells. Cavernous sinus involvement is rare, especially in adults. Here we report an unusual case of a 30-year-old HIV-positive woman with BL and cavernous sinus syndrome who also had intense bilateral breast uptake, related to menstrual cycle. Fluorine-18 2-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) has been found to be useful in the management of BL. PATIENT CONCERNS: A 30-year old female patient presented with a history of diplopia and headache. DIAGNOSES: Magnetic resonance imaging revealed a large cavernous sinus mass. A bone marrow biopsy was done and demonstrated extensive marrow infiltration by Burkitt lymphoma. Further investigation detected the Epstein-Barr virus in her cerebrospinal fluid using qualitative polymerase chain reaction. 18F-FDG PET/CT imaging done revealed a hypermetabolic cavernous sinus mass, conglomerates of enlarged pelvic and para-aortic lymph nodes as well as diffuse bone marrow uptake. Intense bilateral breast uptake was noted coinciding with the start of menses. INTERVENTIONS: She was started on chemotherapy with adjuvant radiotherapy. OUTCOMES: After her first cycle of chemotherapy, repeat 18F-FDG PET/CT imaging revealed a marked reduction in the metabolic activity and size of the cavernous sinus mass and conglomerates of lymph nodes. The bone marrow activity was still visualized but less intense compared to the staging PET/CT. LESSONS: A cavernous sinus mass will rarely be the primary lesion in Burkitt's Lymphoma. Our case demonstrates the role of 18F-FDG PET/CT in the assessment of such cases to detect other primary areas of disease involvement. It is useful in accurate initial staging and monitoring of treatment response in patients with Burkitt's Lymphoma.

Gallium-68-dotatate PET/CT is better than CT in the management of somatostatin expressing tumors: First experience in Africa.

OBJECTIVE: In this study we aimed to present our experience on the use of Gallium-68-dotatate with positron emission tomography, computed tomography (68 Ga-dotatate PET/CT) in the management of neuroendocrine tumors (NET) and other somatostatin expressing tumors. SUBJECTS AND METHODS: We retrospectively reviewed patients with histologically confirmed or biochemically suspected NET and other somatostatin expressing (SSTR) tumors imaged at our department with 68Ga-dotatate PET/CT. We determined the performance of this imaging technique as well as its impact on patients management. A total of 203 patients were studied: 103 females, 100 males median age 52years. RESULTS: The commonest tumor type was gastroenteropancreatic NET (41% of patients) and the commonest sites of distant metastases were lymph nodes and the liver 34.0% and 30.5% respectively. Positron emission tomography detected foci of disease in 19 patients where CT was falsely negative. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 68 Ga-dotatate PET/CT imaging of NET and other SST expressing tumors were 94.16%, 91.89%, 95.55%, 89.47% and 96.55% respectively. CONCLUSION: Gallium-68-dotatate PET/CT was better than CT in detecting primary sites of the disease and highly sensitive and specific for diagnosis and treatment of NET and other SSTR expressing tumors.

18F-FDG PET/CT in the detection of asymptomatic malignant melanoma recurrence.

AIM: To evaluate the diagnostic accuracy of FDG PET/CT in the detection of asymptomatic recurrence in patients with malignant melanoma who have had resection of their primary lesion. We also aimed to determine the pattern and factors predisposing to disease recurrence. METHODS: Patients with malignant melanoma who have had surgical resection of their disease and without any clinical evidence of disease recurrence were followed-up with FDG PET/CT. The diagnostic accuracy of FDG PET/CT, pattern of recurrence and factors predictive of disease recurrence were determined. RESULTS: A total of 144 patients were followed-up for a median period of 50.50 months. Asymptomatic recurrence was seen in 37 patients (25.7 %) with a median time to recurrence of 20 months. Lymph node was the commonest site of asymptomatic recurrence. Sex, tumour depth, histology type and presence of nodal metastasis were significant predictors of tumour recurrence. Age, race, site of primary lesion, type of lymph node resection were not significant predictors of disease recurrence. Race has a significant effect on the histological subtype of tumour (nodular maligna was more common in Caucasian while acral lentiginous was more prevalent in the Blacks) and the site of the primary lesion (lower limb in Blacks and trunk in Caucasians). Sensitivity, specificity and accuracy of FDG PET/CT for the detection of disease recurrence were 94.5 %, 87.6 % and 89.6 % respectively. CONCLUSION: FDG PET/CT is a suitable modality for early detection of asymptomatic recurrence of malignant melanoma. Asymptomatic recurrence most commonly occurs in lymph nodes. Sex, nodal metastasis and tumour pathologic features are predictors of recurrence.