Author Correction: Targeted therapy in patients with PIK3CA-related overgrowth syndrome.

The 'Competing interests' statement of this Article has been updated; see accompanying Amendment for further details.

Targeted therapy in patients with PIK3CA-related overgrowth syndrome.

CLOVES syndrome (congenital lipomatous overgrowth, vascular malformations, epidermal naevi, scoliosis/skeletal and spinal syndrome) is a genetic disorder that results from somatic, mosaic gain-of-function mutations of the PIK3CA gene, and belongs to the spectrum of PIK3CA-related overgrowth syndromes (PROS). This rare condition has no specific treatment and a poor survival rate. Here, we describe a postnatal mouse model of PROS/CLOVES that partially recapitulates the human disease, and demonstrate the efficacy of BYL719, an inhibitor of PIK3CA, in preventing and improving organ dysfunction. On the basis of these results, we used BYL719 to treat nineteen patients with PROS. The drug improved the disease symptoms in all patients. Previously intractable vascular tumours became smaller, congestive heart failure was improved, hemihypertrophy was reduced, and scoliosis was attenuated. The treatment was not associated with any substantial side effects. In conclusion, this study provides the first direct evidence supporting PIK3CA inhibition as a promising therapeutic strategy in patients with PROS.

A Patient-Centered Model of Fast-Track Lung Cancer Diagnosis.

INTRODUCTION: Despite the increasing importance of digital resources in modern life over the past decades, little is known about the impact of internet-based solutions on patient's health. We aimed to study the potential benefit of a digital platform helping patients to deal with abnormal chest CT scan revealing possible lung cancer. METHODS: We set up a fast-track lung cancer diagnosis pathway through a secure online platform. Patient-generated information combined with online review of their imaging enables preplanning of further investigations ahead of clinical assessment. We compared outcomes of "self-referred" patients (patient group), who directly fill out the online questionnaire, to general practitioner-driven patients (GP group), who were referred by their GP. RESULTS: From June 2021 to June 2022, we included 125 patients (61% males, median age 67 years, IQR 56.9-72.5): 41% in the patient group and 59% in the GP group. No difference was found between groups in terms of time from contact to first appointment (median 5 days in both groups, P = .6), percentage of pathways including prebooked tests (94% vs. 92%, P = .6), number of scheduled invasive procedures (median 1, IQR 1-2 vs. 2, IQR 1-2, P = .4) and in final cancer diagnosis (76% vs. 78%, P = .4). CONCLUSION: A lung cancer diagnosis pathway directly accessible by patients through a secure online platform was feasible and as efficient as the usual general practitioner pathway. It demonstrated the benefit of leaning on new digital tools in order to answer to the new challenges of a patient-centered health care system.

18FDG PET Assessment of Therapeutic Response in Patients with Advanced or Metastatic Melanoma Treated with First-Line Immune Checkpoint Inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICI) are currently the first-line treatment for patients with metastatic melanoma. We investigated the value of positron emission tomography (PET) response criteria to assess the therapeutic response to first-line ICI in this clinical context and explore the potential contribution of total tumor metabolic volume (TMTV) analysis. METHODS: We conducted a retrospective study in patients treated with first-line ICI for advanced or metastatic melanoma, with 18F-FDG PET/CT performed at baseline and 3 months after starting treatment. Patients' metabolic response was classified according to PERCIST5 and imPERCIST 5 criteria. TMTV was recorded for each examination. RESULTS: Twenty-nine patients were included. The median overall survival (OS) was 51.2 months (IQR 13.6-not reached), and the OS rate at 2 years was 58.6%. Patients classified as responders (complete and partial response) had a 90.9% 2-year OS rate versus 38.9% for non-responders (stable disease and progressive disease) (p = 0.03), for PERCIST5 and imPERCIST 5 criteria. The median change in metabolic volume was 9.8% (IQR -59-+140%). No significant correlation between OS and changes in TMTV was found. CONCLUSION: The evaluation of response to immunotherapy using metabolic imaging with PERCIST5 and imPERCIST5 was significantly associated with OS in patients with advanced or metastatic melanoma.

"Chronic Disseminated Aspergillosis," a Novel Fungal Immune Reconstitution Inflammatory Syndrome.

We report a case of chronic hepatosplenic aspergillosis following immune reconstitution complicating colic aspergillosis in an AIDS patient with multicentric Castleman disease. Symptoms mimicked the clinical presentation of chronic disseminated candidiasis and responded to corticosteroid. This emerging entity enlarges the spectrum of fungal immune reconstitution inflammatory syndrome in the HIV setting.

Usefulness of 18 F-Labeled Fluorodeoxyglucose-Positron Emission Tomography for the Diagnosis of Lymphoma in Primary Sjögren's Syndrome.

OBJECTIVE: The usefulness of positron emission tomography-computed tomography (PET-CT) with 18 F-labeled fluorodeoxyglucose (18 F-FDG) for the diagnosis of lymphoma in patients with primary Sjögren's syndrome (SS) is unclear, since the abnormalities it reveals may be due to systemic manifestations of SS. This study was undertaken to compare 18 F-FDG-PET-CT in patients with primary SS with lymphoma and those without lymphoma in order to identify patterns associated with lymphoma. METHODS: A retrospective study was conducted in 2 centers and included patients who met the American College of Rheumatology/European League Against Rheumatism 2016 criteria for primary SS and had undergone PET-CT. Two independent readers who were blinded with regard to lymphoma diagnosis analyzed PET-CT scans. Abnormalities were compared between patients with and those without lymphoma. RESULTS: Of the 45 patients included, 15 had lymphoma. Compared to patients without lymphoma, the mean size (P = 0.048) and maximum standardized uptake value (SUVmax) (P = 0.001) of the parotid glands were higher in patients with lymphoma. FDG uptake in the lymph nodes was observed in 53.3% of the patients with lymphoma and 43.3% of the patients without lymphoma, with no difference in the number of sites, uptake pattern, or mean SUVmax. Focal pulmonary uptake (nodules or condensations) was observed in 5 of the patients with lymphoma (33.3%) but only 1 patient without lymphoma (3.3%) (P = 0.01). Having an SUVmax in the parotid gland of ≥4.7 and/or the presence of focal pulmonary lesions was highly suggestive of lymphoma (sensitivity 80%, specificity 83.3%). CONCLUSION: Some systemic manifestations of primary SS (lymphadenopathy, pulmonary involvement, and salivary gland involvement) can be visualized by PET-CT. Involvement of the lymph nodes and parotid glands is commonly observed with a similar frequency in SS patients with and those without lymphoma. An SUVmax in the parotid glands of ≥4.7 and/or the presence of focal lung lesions are associated with the diagnosis of lymphoma.

Prognostic value of early 18F-FDG PET scanning evaluation in immunocompetent primary CNS lymphoma patients.

Primary central nervous system lymphoma (PCNSL) is a rare topographic variant of diffuse large B-cell lymphoma (DLBCL). While prognostic scales are useful in clinical trials, no dynamic prognostic marker is available in this disease. We report here the prognostic value of early metabolic response by 18F-FDG PET scanner (PET) in 25 newly diagnosed immunocompetent PCNSL patients. Induction treatment consisted of four cycles of Rituximab, Methotrexate and Temozolamide (RMT). Based on patient's general condition, consolidation by high-dose Etoposide and Aracytine was given to responding patients. Brain MRI and PET were performed at diagnosis, after two and four cycles of RMT, and after treatment completion. Two-year progression-free (PFS) and overall survival (OS) were 62% and 74%, respectively for the whole cohort. Best responses after RMT induction were 18 (72%) complete response (CR)/CR undetermined (CRu), 4 (16%) partial response, 1 (4%) progressive disease and 2 (8%) stable disease. Response evaluation was concordant between MRI and PET at the end of induction therapy. Nineteen patients (76%) had a negative PET2. Predictive positive and negative values of PET2 on end-of-treatment (ETR) CR were 66.67% and 94.74%, respectively. We observed a significant association between PET2 negativity and ETR (p = 0.001) and longer PFS (p = 0.02), while having no impact on OS (p = 0.32). Two years PFS was 72% and 33% for PET2- and PET2+ patients, respectively (p < 0.02). PET2 evaluation may help to early define a subgroup of CR PCNSL patients with a favorable outcome.

Practical approach for comparative analysis of multilesion molecular imaging using a semiautomated program for PET/CT.

UNLABELLED: We propose a standardized approach to quantitative molecular imaging (MI) in cancer patients with multiple lesions. METHODS: Twenty patients with castration-resistant prostate cancer underwent (18)F-FDG and (18)F-16ß-fluoro-5-dihydrotestosterone ((18)F-FDHT) PET/CT scans. Using a 5-point confidence scale, 2 readers interpreted coregistered scan sets on a workstation. Two hundred three sites per scan (specified in a lexicon) were reviewed. (18)F-FDG-positive lesion bookmarks were propagated onto (18)F-FDHT studies and then manually accepted or rejected. Discordance-positive (18)F-FDHT lesions were similarly bookmarked. Lesional SUV(max) was recorded. Tracer- and tissue-specific background correction factors were calculated via receiver-operating-characteristic analysis of 65 scan sets. RESULTS: Readers agreed on more than 99% of (18)F-FDG- and (18)F-FDHT-negative sites. Positive-site agreement was 83% and 85%, respectively. Consensus-lesion maximum standardized uptake value (SUV(max)) was highly reproducible (concordance correlation coefficient > 0.98). Receiver-operating-characteristic curves yielded 4 correction factors (SUV(max) 1.8-2.6). A novel scatterplot (Larson-Fox-Gonen plot) depicted tumor burden and change in SUV(max) for response assessments. CONCLUSION: Multilesion molecular imaging is optimized with a 5-step approach incorporating a confidence scale, site lexicon, semiautomated PET software, background correction, and Larson-Fox-Gonen graphing.