PIK3CA copy-number gain and inhibitors of the PI3K/AKT/mTOR pathway in triple-negative breast cancer.

As wider insights are gained on the molecular landscape of triple-negative breast cancer (TNBC), novel targeted therapeutic strategies might become an option in this setting as well. Activating mutations of PIK3CA represent the second most common alteration in TNBC after the TP53 mutation, with a prevalence of ∼10%-15%. Considering the well-established predictive role of PIK3CA mutations for response to agents targeting the PI3K/AKT/mTOR pathway, several clinical trials are currently evaluating these drugs in patients with advanced TNBC. However, much less is known regarding the actionability of PIK3CA copy-number gains, which represent a thoroughly common molecular alteration in TNBC, with a prevalence estimated at 6%-20%, and are listed as "likely gain-of-function" alterations in the OncoKB database. In the present paper, we describe two clinical cases in which patients harboring PIK3CA-amplified TNBC received a targeted treatment with the mTOR-inhibitor everolimus and the PI3K-inhibitor alpelisib, respectively, with evidence of disease response on 18F-FDG positron-emission tomography (PET) imaging. Hence, we discuss the evidence presently available regarding a possible predictive value of PIK3CA amplification for response to targeted treatment strategies, suggesting that this molecular alteration might represent an intriguing biomarker in this sense. Considering that few of the currently active clinical trials assessing agents targeting the PI3K/AKT/mTOR pathway in TNBC select patients based on tumor molecular characterization, and none of these based on PIK3CA copy-number status, we urge for the introduction of PIK3CA amplification as a criterion for patient selection in future clinical trials in this setting.

A single-center, multidisciplinary experience with radium-223 dichloride in men with metastatic castrate-resistant prostate cancer.

INTRODUCTION: We aimed to investigate several clinical and biochemical parameters, including palliative external beam radiation therapy (EBRT) to predict survival in patients with metastatic castrate-resistant prostate cancer (mCRPC) treated with radium-223 (223Ra). METHODS: We tested known and possible prognostic parameters, including palliative EBRT, both prior and concurrent to 223Ra. Logrank test (Kaplan-Meier method) and Cox regression analysis were used to predict overall survival (OS). RESULTS: A total of 133 patients were treated with 223Ra; median age was 72 years. Median OS was 9.0 (95% confidence interval [CI] 7.4-10.6) months. By univariate analysis (log-rank test), baseline Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 (p=0.001), ≥5 cycles of 223Ra (p<0.001), baseline hemoglobin (Hb) ≥120 g/L (p <0.001), baseline total alkaline phosphatase (tALP) <110 U/L (p=0.001), and any prostate-specific antigen (PSA) decline at week 12 (p=0.013) were associated with increased OS. EBRT prior and/or concurrent to 223Ra showed a trend (p=0.051) towards inferior OS by univariate analysis only. By multivariate analysis, significant factors were PS 0-1 (hazard ratio [HR] 1.94, 95% CI 1.3-2.9, p=0.001), Hb ≥120 g/L (HR 0.5, 95% CI 0.3-0.9, p=0.011), and absence of docetaxel use prior to 223Ra (HR 1.86, 95% CI 1.08-3.22, p=0.026). With baseline Hb, tALP, and ECOG PS, we were able to divide patients into three groups with different median OS (months): 23.0 (95% CI 12.8-33.2), 8.0 (95% CI 6.7-9.3), and 5.0 (95% CI 3.1-6.9) for low-, intermediate-, and high-risk, respectively (p<0.001). CONCLUSIONS: We found that 223Ra therapy can result in an OS of close to two years in carefully selected patients. Earlier administration of 223Ra therapy to fitter patients with mCRPC should be tested.

Oligometastatic Disease Detection with 68Ga-PSMA-11 PET/CT in Hormone-Sensitive Prostate Cancer Patients (HSPC) with Biochemical Recurrence after Radical Prostatectomy: Predictive Factors and Clinical Impact.

Metastasis-directed therapy (MDT) in oligometastatic prostate cancer has the potential of delaying the start of androgen deprivation therapy (ADT) and disease progression. We aimed to analyze the efficacy of PSMA-PET/CT in detecting oligometastatic disease (OMD), to look for predictive factors of OMD, and to evaluate the impact of PSMA-PET/CT findings on clinical management. We retrospectively analyzed a homogeneous population of 196 hormone-sensitive prostate cancer patients (HSPC), considered potential candidates for MDT, with a PSMA-PET/CT performed at biochemical recurrence (BCR) after radical prostatectomy (RP). Multivariable logistic regression analysis was performed based on several clinico-pathological factors. Changes in clinical management before and after PSMA-PET/CT were analyzed. The OMD detection rate was 44% for a total positivity rate of 60%. PSMA-PET/CT positivity was independently related to PSA (OR (95% CI), p) (1.7 (1.3-2.3), p < 0.0001) and PSAdt (0.4 (0.2-0.8), p = 0.013), and OMD detection was independently related to PSA (1.6 (1.2-2.2), p = 0.001) and no previous salvage therapy (0.3 (0.1-0.9), p = 0.038). A treatment change was observed in 58% of patients, mostly to perform MDT after OMD detection (60% of changes). This study showed that PSMA-PET/CT is an excellent imaging technique to detect OMD early in HSPC patients with BCR after RP, changing therapeutic management mostly into MDT.

Colon Adenocarcinoma Associated With Clostridium Septicum Endophthalmitis Detected on 18F-FDG PET/CT.

Endogenous Clostridium septicum endophthalmitis is a rare and fulminant ocular infection, usually encountered in immunocompromised or diabetic patients. It is also highly associated with both gastrointestinal and hematologic malignancies. We describe herein the detection of an adenocarcinoma of the cecum on PET/CT with F-FDG in a patient with an active endogenous C. septicum endophthalmitis of the right eye. FDG PET/CT should be considered for all patients with endogenous endophthalmitis to exclude an occult malignancy, especially colorectal cancer.

Case Report 18F-FDG PET/CT of Pseudomyogenic Hemangioendothelioma.

Hemangioendotheliomas are a heterogeneous group of vascular neoplasm that may affect the liver, bone, and soft tissues. Among its variants, pseudomyogenic hemangioendothelioma is rarely encountered. Pseudomyogenic hemangioendothelioma is usually characterized by multiple soft tissue lesions, with occasional bone lesions. Fewer than 20 cases with exclusive involvement of bone structures have been reported. We describe a case of pseudomyogenic hemangioendothelioma involving multiple bony structures but without soft tissue involvement in a 7-year-old girl, imaged with F-FDG PET/CT at diagnosis and during treatment with mammalian target of rapamycin inhibitors.

Low 68Ga-PSMA PET/CT Uptake in Chronic Intramuscular Nodular Fasciitis.

Nodular fasciitis is an uncommon benign mass-forming myofibroblastic proliferation, most frequently found in the upper limbs, with only rare intramuscular cases. We describe herein a case of chronic nodular fasciitis of the left triceps muscle with a low Ga-labeled prostate-specific membrane antigen (PSMA) ligand uptake on PET/CT. Ga-PSMA ligands bind to PSMA-expressing prostate cancer cells, but uptake has also been demonstrated in other solid neoplasms and various benign lesions. Nodular fasciitis should be included in the differential diagnosis of soft tissue lesions with variable Ga-PSMA uptake.

Early Detection of Metastatic Prostate Cancer Relapse on 68Ga-PSMA-11 PET/CT in a Patient Still Exhibiting Biochemical Response.

Prostate cancer (PCa) treatment monitoring usually relies on prostate-specific antigen to detect disease progression or relapse. PET/CT with prostate-specific membrane antigen (PSMA) ligands has shown high accuracy in detecting metastatic PCa lesions and could help assess response to therapy. We describe herein the early relapse detection of a hormone-sensitive metastatic upfront PCa treated with docetaxel on Ga-PSMA-11 PET/CT before biochemical progression. PSMA PET/CT should be considered to monitor PCa response to chemotherapy to detect early relapse, regardless of prostate-specific antigen levels, increasing the chances of finding low-volume oligoprogressive disease.

Incidental Detection of a Giant Fecaloma on 18F-FDG PET/CT.

Fecal retention can be exacerbated in older patients, bedridden patients, as well as those receiving opioids analgesics or anticholinergic medications. It can lead to impaction, which can have serious consequences, sometimes even requiring surgical intervention. We describe herein the incidental detection of a giant hypometabolic fecaloma on PET/CT with F-FDG during the initial staging of a patient with osteosarcoma using opioids for pain management.

Evaluation of PSMA expression changes on PET/CT before and after initiation of novel antiandrogen drugs (enzalutamide or abiraterone) in metastatic castration-resistant prostate cancer patients.

OBJECTIVE: To investigate the association between Prostate-Specific Membrane Antigen (PSMA) expression changes on positron emission tomography-computed tomography (PET/CT) and the response to treatment following the start of enzalutamide or abiraterone in metastatic castration-resistant prostate cancer (mCRPC) patients. METHODS: All consecutive 68Ga-PSMA-11 PET/CT scans routinely performed at our institution during more than 4 years were retrospectively screened for inclusion. We included mCRPC patients with a baseline PSMA PET/CT performed less than 2 months before the start of either enzalutamide or abiraterone, and a follow-up PSMA PET/CT performed no more than a year after, while still under those novel antiandrogen drugs (NAD). The associated clinical records were reviewed. Patients were considered treatment responders if they presented decreasing PSA levels > 50% or a radiological response based on RECIST 1.1 criteria. PSMA expression changes on the follow-up PET/CT were assessed using per-patient dominant response criteria to classify patients as PSMA-responders (complete disappearance of pathologic PSMA uptake, or a decreased uptake of the majority of lesions) or PSMA-non-responders (new PSMA-expressing lesions, increased uptake of the majority of lesions, or stable PSMA expression of the disease). Descriptive statistics and measures of associations (two-sided Fisher's exact test and Phi coefficient) were calculated. RESULTS: A total of 11 and 15 patients were included in the enzalutamide and abiraterone groups. Median follow-up was 110 (IQR 76-124) and 87 (IQR 71-242) days, respectively. All treatment responders (3 enzalutamide and 4 abiraterone) were considered PSMA-responders, and all treatment non-responders (8 enzalutamide, 11 abiraterone) were considered PSMA-non-responders. PSMA PET response was thus perfectly associated with conventional response criteria (p = 0.006, Phi = 1 for enzalutamide; p = 0.001, Phi = 1 for abiraterone). In our cohort, no PSMA expression flare phenomenon was detected on follow-up PET/CT scans at a median follow-up of 3 months. However, an early and short-lived flare cannot be excluded. CONCLUSIONS: This retrospective study suggests that, after a median follow-up of 3 months under enzalutamide or abiraterone, PSMA expression changes on PET/CT are strongly associated with response to treatment. Prospective studies are needed to better understand PSMA expression dynamics following the start of enzalutamide and abiraterone, along with the role of PSMA PET/CT in response assessment.

Incidental Detection of a Radiation-Induced Soft-Tissue Sarcoma on 68Ga-PSMA PET/CT in a Patient Previously Treated for Prostate Cancer.

Radiation-induced sarcoma is a rare complication of radiation therapy. We describe the incidental detection of a radiation-induced undifferentiated soft-tissue sarcoma with increased uptake on Ga-labeled prostate-specific membrane antigen (PSMA) PET/CT in a prostate cancer patient previously treated with surgery and external-beam radiotherapy. Results were confirmed by histological analysis. Ga-PSMA is known to bind not only to PSMA-expressing prostate cancer cells but also to the neovasculature of various other solid tumors. A careful Ga-PSMA PET/CT review of previously irradiated areas is warranted so as not to miss radiation-induced sarcoma in prostate cancer patients.

Heterogeneity of 68Ga-PSMA PET/CT Uptake in Fibrous Dysplasia.

Fibrous dysplasia is an uncommon benign bone pathology with only rare potential for malignant transformation. We describe the heterogeneous uptake of fibrous dysplasia of a whole rib on Ga-labeled prostate-specific membrane antigen (PSMA) PET/CT. Ga-PSMA binds to PSMA-expressing prostate cancer cells, but it can also bind to the neovasculature of various solid tumors, as well as to some benign lesions. Ga-PSMA expression in fibrous dysplasia should not automatically be equated with malignant transformation or confused with prostate cancer metastases.

Clinical relevance of 18F-FDG PET/CT lower-limb imaging in patients with malignant cutaneous melanoma.

OBJECTIVE: The aim of this study was to assess the clinical relevance of imaging the lower limbs when using 2-(F)-fluoro-2-deoxy-D-glucose (F-FDG) positron emission tomography with computed tomography (PET/CT) for malignant cutaneous melanoma in patients without previously known or suspected primary or metastatic melanoma lesions in the lower limbs. PATIENTS AND METHODS: We retrospectively assessed 880 consecutive F-FDG PET/CT scans performed for adult patients in a context of suspected melanoma spanning a period of 5 years. All scans were correlated with the associated patient records (clinical history, physical examinations, and pathology reports), as well as follow-up imaging examinations, up until at least 6 months after the end of the study. RESULTS: Among the 461 whole-body scans included for analysis, 109 reported unusual activity in the lower limbs, but with at most 21 scans showing lower-limb lesions attributed to melanoma on follow-up. No scan showed melanoma lesions exclusively in the lower limbs, and in no case did imaging the lower limbs upstage a patient. Imaging the lower limbs changed the actual clinical management of the melanoma for only one patient, with precautionary local radiation therapy administered following the detection of an asymptomatic distal femur bone metastasis in an otherwise plurimetastatic patient headed for palliative care. CONCLUSION: Our study, the largest of its kind, confirms that, when using F-FDG PET/CT for staging, restaging, or surveillance of malignant cutaneous melanoma in patients without previously known or suspected lower-limb melanoma lesions, imaging the lower extremities offers little additional clinically relevant information and stopping the scan at the proximal thighs has essentially no clinical impact.