18F-FDG-PET/CT imaging of uterine cervical cancer recurrence in women with and without HIV infection.

BACKGROUND: To compare the rate, time and, pattern of recurrence of cervical cancer between patients with and without HIV infection and to determine factors predicting cervical cancer recurrence in patients evaluated by 18F-FDG-PET/CT. METHODS: We reviewed the 18F-FDG-PET/CT images of patients with histologically proven cervical carcinoma who were presenting with suspected recurrence. We extracted epidemiologic data, previous treatment, histologic subtype, HIV status, viral load and CD4 counts from the electronic laboratory database and the referral form for the 18F-FDG-PET/CT study. RESULTS: We studied 303 women including 112 HIV-infected patients. FIGO stage III disease was present in 131 patients. Of 198 patients with recurrence, 74 were HIV-infected while 124 were not (P=0.849). HIV infected patients were younger (41.99±9.30 years) compared to HIV-uninfected (50.19±11.09), P<0.001. Local recurrence was present in 125 patients while 100 patients had a distant recurrence. Recurrence occurred at a single site in 88 patients and two or more sites in 110 patients. No significant difference in the recurrent patterns between HIV-infected and uninfected patients. Median time to recurrence was 10.50 months (range: 6.00-156.00) among HIV-infected versus 12.00 months (IQR:7.00-312.00) among the uninfected, P=0.065. FIGO stage III (P=0.042) and the presence of histological sub-types other than SCC (P=0.005) were significant predictors of recurrence. HIV infection by itself was not significant in predicting recurrence (P=0.843). CONCLUSIONS: HIV infection has no significant impact on the rate, time or pattern of recurrence in women with suspected cervical carcinoma recurrence. Advanced disease and histological variant other than SCC are predictive of recurrence.

Immune Checkpoints, Inhibitors and Radionuclides in Prostate Cancer: Promising Combinatorial Therapy Approach.

Emerging research demonstrates that co-inhibitory immune checkpoints (ICs) remain the most promising immunotherapy targets in various malignancies. Nonetheless, ICIs have offered insignificant clinical benefits in the treatment of advanced prostate cancer (PCa) especially when they are used as monotherapies. Current existing PCa treatment initially offers an improved clinical outcome and overall survival (OS), however, after a while the treatment becomes resistant leading to aggressive and uncontrolled disease associated with increased mortality and morbidity. Concurrent combination of the ICIs with radionuclides therapy that has rapidly emerged as safe and effective targeted approach for treating PCa patients may shift the paradigm of PCa treatment. Here, we provide an overview of the contextual contribution of old and new emerging inhibitory ICs in PCa, preclinical and clinical studies supporting the use of these ICs in treating PCa patients. Furthermore, we will also describe the potential of using a combinatory approach of ICIs and radionuclides therapy in treating PCa patients to enhance efficacy, durable cancer control and OS. The inhibitory ICs considered in this review are cytotoxic T-lymphocyte antigen 4 (CTLA4), programmed cell death 1 (PD1), V-domain immunoglobulin suppressor of T cell activation (VISTA), indoleamine 2,3-dioxygenase (IDO), T cell Immunoglobulin Domain and Mucin Domain 3 (TIM-3), lymphocyte-activation gene 3 (LAG-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT), B7 homolog 3 (B7-H3) and B7-H4.

Diagnostic sensitivity of Tc-99m HYNIC PSMA SPECT/CT in prostate carcinoma: A comparative analysis with Ga-68 PSMA PET/CT.

BACKGROUND: Emerging data from published studies are demonstrating the superiority of Ga-68 PSMA PET/CT imaging in prostate cancer. However, the low yield of the Ge-68/Ga-68 from which Gallium-68 is obtained and fewer installed PET/CT systems compared to the SPECT imaging systems may limit its availability. We, therefore, evaluated in a head-to-head comparison, the diagnostic sensitivity of Ga-68 PSMA PET/CT and Tc-99m PSMA SPECT/CT in patients with prostate cancer. METHODS: A total of 14 patients with histologically confirmed prostate cancer were prospectively recruited to undergo Ga-68 PSMA PET/CT and Tc-99m HYNIC PSMA SPECT/CT. The mean age of patients was 67.21 ± 8.15 years and the median PSA level was 45.18 ng/mL (range = 1.51-687 ng/mL). SUVmax of all lesions and the size of lymph nodes with PSMA avidity on Ga-68 PSMA PET/CT were determined. Proportions of these lesions detected on Tc-99m HYNIC PSMA SPECT/CT read independent of PET/CT findings were determined. RESULTS: A total of 46 lesions were seen on Ga-68 PSMA PET/CT localized to the prostate (n = 10), lymph nodes (n = 24), and bones (n = 12). Of these, Tc-99m HYNIC PSMA SPECT/CT detected 36 lesions: Prostate = 10/10 (100%), lymph nodes = 15/24 (62.5%), and bones = 11/12 (91.7%) with an overall sensitivity of 78.3%. Lesions detected on Tc-99m HYNIC PSMA SPECT/CT were bigger in size (P < 0.001) and had higher SUVmax (P < 0.001) as measured on Ga-68 PSMA PET/CT compared to those lesions that were not detected. All lymph nodes greater than 10 mm in size were detected while only 28% of nodes less than 10 mm were detected by Tc-99m HYNIC PSMA SPECT/CT. In a univariate analysis, Lymph node size (P = 0.033) and the SUVmax of all lesions (P = 0.007) were significant predictors of lesion detection on Tc-99m HYNIC PSMA SPECT/CT. CONCLUSION: Tc-99m HYNIC PSMA may be a useful in imaging of prostate cancer although with a lower sensitivity for lesion detection compared to Ga-68 PSMA PET/CT. Its use is recommended when Ga-68 PSMA is not readily available, in planning radio-guided surgery or the patient is being considered for radio-ligand therapy with Lu-177 PSMA. It performs poorly in detecting small-sized lesions hence its use is not recommended in patients with small volume disease.

The role of F-18 FDG PET/CT in evaluating the impact of HIV infection on tumor burden and therapy outcome in patients with Hodgkin lymphoma.

BACKGROUND: To evaluate the impact of HIV infection on tumor burden and therapy outcome following treatment with chemotherapy in patients with Hodgkin lymphoma. METHODS: A total of 136 patients with classical Hodgkin lymphoma were studied (mean age ± SD = 32.31 ± 1.39 years, male = 86, female = 50). Advanced disease (stage III and IV) was present in 64% of patients. HIV infection was present in 57 patients while 79 patients were HIV-negative. Baseline F-18 FDG PET/CT was obtained in all patients. SUVmax, MTV and TLG were determined on the baseline scan to evaluate for tumor burden. All patients completed a standard regimen of adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). After a median period of 8 weeks (range = 6 to 17 weeks), a repeat F-18 FDG PET/CT scan was obtained to evaluate response to therapy using Deauville 5-point scoring system. RESULTS: The HIV-positive and HIV-negative groups were similar with regards to age and disease stage. The groups were heterogeneous with respect to gender (p = 0.029). The SUVmax, MTV and TLG of lesions were not significant different between the two groups. Complete response was seen in 72.8% of the study population. Presence of HIV infection was associated with higher rate of treatment failure with 40.4% of the HIV-positive patients having treatment failure while only 17.7% of the HIV-negative patients had treatment failure (p = 0.0034). HIV infection was a significant predictor of response to chemotherapy. Effects of SUVmax, MTV, TLG and Ann Arbor stage of the disease were not statistically significant as predictors of therapy outcome. In a multiple logistic regression, presence of HIV infection still remained an independent predictor of therapy outcome in the presence of other factors such as SUVmax, MTV, TLG and the Ann Arbor stage of the disease. CONCLUSIONS: HIV infection is not associated with a higher tumor burden in patients with Hodgkin lymphoma. HIV infection is, however, a strong predictor of poor therapy outcome in patients treated with standard regimen of ABVD.

A comparison of 18F-FDG PET/CT findings in HIV positive compared to HIV negative patients with recurrent cervical cancer.

OBJECTIVE: HIV-positive women with cervical cancer have higher recurrence and death rates with shorter time to recurrence and death compared with HIV-negative subjects. The objective of this study was to compare the recurrence patterns in HIV-positive women with invasive cervical cancer to their HIV-negative counterparts using 18F-FDG PET/CT. SUBJECTS AND METHODS: We evaluated 40 HIV- seropositive and 79 HIV-seronegative patients with recurrent cervical carcinoma using 18F-FDG PET/CT. The PET/CT datasets were interpreted by two independent readers blinded to the HIV status of the patients. Areas of disagreement were resolved by consensus. Cervical cancer recurrence was confirmed by biopsy and histological examination of tissue, correlation with conventional imaging (CT and MRI) and by follow-up 18F-FDG PET/CT. RESULTS: HIV-positive patients were 9 years younger than the HIV-negative patients at the time of diagnosis; mean age 39 years versus 48 years respectively. Initial treatment was comparable in both groups. Time to recurrence was shorter in HIV-infected compared with HIV-uninfected women (11 versus 24 months). The commonest sites of metastatic recurrence was in the lymph nodes. HIV-infected patients demonstrated significant higher recurrence in lymph nodes and lungs (P<0.05). No significant difference in the recurrence rate in liver or bone (P>0.05) between both groups. HIV-infected patients showed unusual metastases to brain, spleen and skin. CONCLUSION: By using the 18F-FDG PET/CT scan we showed that the time to recurrence is shorter among HIV seropositive patients with the commonest site of metastatic recurrence being in the lymph nodes. Nodal and liver metastases are significantly higher in HIV seropositive patients compared with seronegative patients.

The Association of Tumor Burden by 18F-FDG PET/CT and Survival in Vulvar Carcinoma.

PURPOSE: The aim of this study was to assess the impact of 18F-FDG PET/CT metabolic parameters obtained at initial staging of vulva carcinoma on survival in women with and without HIV infection. PATIENTS AND METHODS: 18F-FDG PET/CT images of women with vulva cancer who are planned for definitive therapy were analyzed. SUVmax, SUVmean, MTV, and total lesion glycolysis (TLG) as well as whole-body MTV and whole-body TLG were computed. RESULTS: Twenty-five women were included with a mean age of 43.44 ± 10.32. The majority of the patients were HIV infected with a median CD4 count of 444.00 cells/mm3. The HIV-infected women are younger at diagnosis than their HIV-uninfected counterparts. All patients presented with inguinofemoral lymph node involvement, whereas half the patients had pelvic nodal metastasis. All the patients with distant visceral or skeletal metastasis were HIV infected. The lungs were the most common site of distant metastasis. When comparing the SUVmax, SUVmean, MTV, TLG, wbMTV, and wbTLG between HIV-infected and HIV-uninfected patients, we did not find statistical differences. Twelve patients (48%) were upstaged to metastatic disease. Seven patients had died at the time of analysis. The wbMTV and wbTLG were significantly higher in nonsurvivors than survivors. CONCLUSIONS: 18F-FDG PET/CT improves initial staging of squamous cell carcinoma among women with and without HIV infection. The whole-body tumor burden assessed by 18F-FDG PET metabolic metrics did not differ between HIV-infected and HIV-uninfected women. A higher whole-burden tumor burden is associated with a higher risk of mortality among women with vulva cancer.

18F-FDG PET/CT imaging of vulva cancer recurrence: A comparison of PET-derived metabolic parameters between women with and without HIV infection.

OBJECTIVE: To assess the patterns of recurrence of vulva cancer on 18F-FDG PET/CT and to compare the 18F-FDG PET metabolic metrics in patients with and without Human Immunodeficiency Virus (HIV). METHODS: Maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumour volume (MTV and total lesion glycolysis (TLG) were obtained on Flourine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) images of women referred with suspected or confirmed vulva cancer recurrence. We compared HIV-infected and HIV-uninfected patients regarding pattern disease recurrence, age at diagnosis, and the PET-derived metabolic indices. RESULTS: We analyzed 33 patients with a mean age 50.76 ± 15.78 including 21 HIV-infected women. The majority of patients (94 %) had squamous cell carcinoma and 84.85 % were Blacks. Of the HIV-infected individuals, the median CD4 count was 526.0 cells/mm3 (IQR: 379.0-729.0). HIV infected patients were younger than the HIV uninfected at the time of diagnosis: 40.50 ±â€Š8.87 vs 66.54 ±â€Š9.71 respectively, p < 0.001. We found a local (vulvar) recurrence rate of 75.8 %. Nodal pelvic recurrences were higher in the HIV-infected patients than in the HIV uninfected patients (70 % vs 30 %, p = 0.027). Three patients had distant metastasis and all three were HIV-infected. There was a higher whole-body MTV and TLG among HIV-infected women compared with HIV-uninfected women, 103.39 vs 17.58 and 852.64 vs 101.79, respectively (p < 0.05 for both). CONCLUSION: HIV-infected women are diagnosed with vulva cancer at a younger age. HIV-infected patients had a higher rate of pelvic lymph node recurrence. There is a higher tumor burden at vulva cancer recurrence among women with HIV infection.

Prognostic Value of Pre-treatment F-18 FDG PET Metabolic Metrics in Patients with Locally Advanced Carcinoma of the Anus with and without HIV Infection.

AIM: To investigate the prognostic value of F-18 FDG PET metabolic parameters in patients with anal carcinoma with and without human immunodeficiency virus infection (HIV). METHODS: Maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were obtained on F-18 FDG PET/CT images of treatment-naïve patients with locally advanced anal squamous cell carcinoma (ASSC). We compared patients' characteristics and F-18 FDG PET metabolic metrics between the HIV-infected patients and the HIV-uninfected patients. We did a simple Cox regression analysis followed by a multiple Cox regression analysis to determine factors predictive of death. RESULTS: We studied 33 patients including 21 HIV-infected individuals, mean age = 46.06 ± 12.59, female = 16, males = 17. Median CD4 count among HIV-infected patients was 400.50 cells/mm3 (IQR: 304.0 - 642.25). HIV-infected patients were younger than the HIV-uninfected patients at the time of diagnosis; 38.71 ± 7.98 vs. 58.92 ± 7.88 respectively, p < 0.001. No significant difference in the TNM stage and F-18 FDG metabolic parameters between the two groups. In a simple Cox regression analysis, MTV and TLG were significant predictors of death. Following a multiple Cox regression analysis, MTV and SUVmean were significant predictors of death. The median overall survival was 44.63 (95 % CI: 34.12 - 55.14) among HIV-infected patients versus 54.65 (95 % CI: 45.73 - 63.57) among HIV-uninfected patients, p = 0.415. CONCLUSION: HIV-infected patients are diagnosed with ASSC at a younger age compared with HIV-uninfected patients. F-18 FDG PET metabolic metrics especially MTV predicts overall survival in patients with ASCC. There is no difference in the overall survival of HIV-infected and HIV-uninfected patients treated similarly for ASSC. ZIEL:: Die Untersuchung der prognostischen Bedeutung der F-18 FDG PET metabolischen Aktivität bei HIV-negativen und positiven Analkarzinom-Patienten. METHODEN: Bestimmt wurden maximale standardisierten Uptake-Werte (SUVmax), mittlere standardisierte Uptake-Werte (SUVmean), das metabolische Tumorvolumen (MTV) sowie die gesamte Tumorlyse-Glukose (TLG) mittels F-18 FDG PET/CT bei behandlungsnaiven Patienten mit lokal fortgeschrittenem Anal-Plattenepithelkarzinom (ASSC). Die Patientencharakteristika und F-18 FDG PET metabolischen Ergebnisse der HIV-positiven und HIV-negativen Patienten wurden verglichen. Eine einfache Cox-Regressionsanalyse gefolgt von einer multiplen Cox-Regressionsanalyse diente der Bestimmung von Faktoren für Tod. ERGEBNISSE: Wir untersuchten 33 Patienten, davon 21 HIV-Infizierte, mittleres Alter = 46,06 ± 12,59, Frauen = 16, Männer = 17. Die mediane CD4-Zahl unter den HIV-Patienten war 400,50 Zellen/mm3 (IRQ: 304,0 - 642,25). Die HIV-infizierten Patienten waren jünger als die HIV-negativen Patienten zum Zeitpunkt der Diagnose; 38,71 ± 7,98 vs. 58,92 ± 7,88, p < 0,001. Es gab keinen signifikanten Unterschied in der TNM-Klassifikation und in den F-18 FDG metabolischen Werten zwischen den beiden Gruppen. In einer einfachen Cox-Regressionsanalyse waren MTV und TLG signifikante Prädiktoren für Tod. Das mediane Gersamtüberleben lag bei 44,63 (95 % CI: 34,12 - 55,14) unter den HIV-infizierten Patienten vs. 54,65 (95 % CI: 45,73 - 63,57) unter den HIV-negativen Patienten, p = 0,415. SCHLUSSFOLGERUNGEN: HIV-infizierte Patienten werden in jüngeren Jahren mit ASSC diagnostiziert im Vergleich zu HIV-negativen Patienten. F-18 FDG PET metabolische Aktivität, insbesondere MTV, kann das Gesamtüberleben von Patienten mit ASCC vorhersagen. Es gibt keinen Unterschied im Gesamtüberleben von HIV-infizierten und HIV-negativen Patienten bei gleicher Therapie des ASSC.

68Ga-PSMA PET/CT Replacing Bone Scan in the Initial Staging of Skeletal Metastasis in Prostate Cancer: A Fait Accompli?

PURPOSE: 68Ga ligands targeting prostate-specific membrane antigen (PSMA) are rapidly emerging as a significant step forward in the management of prostate cancer. PSMA is a type II transmembrane protein with high expression in prostate carcinoma cells. We prospectively evaluated the use of 68Ga-PSMA positron emission tomography/computed tomography (PET/CT) in patients with prostate cancer and compared the results to those for technetium-99m (99mTc)-10-metacyloyloxydecyl dihydrogen phosphate (MDP) bone scintigraphy (BS). PATIENTS AND METHODS: A total 113 patients with biopsy-proven prostate cancer referred for standard-of-care BS were prospectively enrolled onto this study. 68Ga-PSMA PET/CT was performed after BS. Metastasis diagnosed on each technique was compared against a final diagnosis based on CT, magnetic resonance imaging, skeletal survey, clinical follow-up, and histologic correlation. RESULTS: Ninety-one bone lesions were interpreted as bone metastases in 25 men undergoing 68Ga-PSMA PET/CT compared to only 61 lesions in 19 men undergoing 99mTc-MDP BS. Of the 7 bone scans that missed skeletal metastases, 54% of these missed lesions were due to either marrow or lytic skeletal metastases. The median standardized uptake value in all malignant bone lesions was 13.84. 68Ga-PSMA PET/CT showed significantly higher sensitivity and accuracy than BS (96.2% vs. 73.1%, and 99.1% vs. 84.1%) for the detection of skeletal lesions. For extraskeletal lesions, 68Ga-PSMA PET/CT showed an additional 96 unexpected lesions with a median standardized uptake value of 17.6. CONCLUSION: 68Ga-PSMA PET/CT is superior to and can potentially replace bone scan in the evaluation for skeletal metastases in the clinical and trial setting because of its ability to detect lytic and bone marrow metastases.

Higher preablative serum thyroid-stimulating hormone level predicts radioiodine ablation effectiveness in patients with differentiated thyroid carcinoma.

INTRODUCTION: Radioiodine ablation of remnant thyroid tissue is an important adjuvant therapy of differentiated thyroid carcinoma (DTC) after thyroidectomy. Elevated serum thyroid-stimulating hormone (TSH) level is necessary for successful ablation. The optimum level of serum TSH level necessary for successful radioiodine ablation of well-DTC is, however, yet to be defined. We aimed to determine whether higher serum TSH level will result in a better rate of complete ablation of well-DTC using iodine-131 (I) following initial thyroidectomy. PATIENTS AND METHODS: A total of 109 patients with differentiated thyroid cancer were divided into four treatment groups on the basis of serum TSH levels. They were followed up from 6 to 12 months after treatment with stimulated serum thyroglobulin level and a diagnostic whole-body scan with radioactive iodine I to determine early response. RESULTS: Sixty-four patients had papillary thyroid carcinoma, whereas 45 patients had follicular carcinoma. An excellent response was observed in 66.7% of patients with TSH level more than 90 µIU/ml, 72.2% in the group with TSH level of 60-89 µIU/ml, 48.5% when TSH was 30-59 µIU/ml and 26.7% when TSH was less than 30 µIU/ml (P=0.002). CONCLUSION: Higher preablative serum TSH predicts a better rate of ablation in patients with differentiated thyroid cancer treated with I after thyroidectomy.