Reliability of Alkaline Phosphatase for Differentiating Flare Phenomenon from Disease Progression with Bone Scintigraphy

The flare phenomenon (FP) on bone scintigraphy after the initiation of systemic treatment seriously complicates evaluations of therapeutic response in patients with bone metastases. The aim of this study was to evaluate whether serum alkaline phosphatase (ALP) can differentiate FP from disease progression on bone scintigraphy in these patients. Breast or prostate cancer patients with bone metastases who newly underwent systemic therapy were reviewed. Pretreatment baseline and follow-up data, including age, pathologic factors, type of systemic therapy, radiologic and bone scintigraphy findings, and ALP levels, were obtained. Univariate and multivariate analyses of these factors were performed to predict FP. An increased extent and/or new lesions were found in 160 patients on follow-up bone scintigraphy after therapy. Among the 160 patients, 80 (50%) had an improvement on subsequent bone scintigraphy (BS), while subsequent scintigraphy also showed an increased uptake in 80 (50%, progression). Multiple regression analysis revealed that stable or decreased ALP was an independent predictor for FP (p < 0.0001). ALP was an independent predictor for FP on subgroup analysis for breast and prostate cancer (p = 0.001 and p = 0.0223, respectively). Results of the study suggest that ALP is a useful serologic marker to differentiate FP from disease progression on bone scintigraphy in patients with bone metastasis. Clinical interpretation for scintigraphic aggravation can be further improved by the ALP data and it may prevent fruitless changes of therapeutic modality by misdiagnosis of disease progression in cases of FP.

Toxic flare phenomenon in osteoblastoma: A case report with literature review

Osteoblastomas are benign neoplasm of the bone that is characterized by clinical and histological similarity to osteoid osteomas. They are larger (>1.5–2 cm) and tend to affect the axial skeleton. Patients typically present commonly in the second or third decades of life with a male predilection. The flare phenomenon in osteoblastoma is a rare but known entity showing florid multifocal periostitis. Few cases have been reported in the literature. Focally aggressive osteoblastomas also present with flare phenomenon mediated by prostaglandin-induced inflammation. We report a strikingly unusual case of an osteoblastoma of the spine in a 23-year-old male patient who presented in our outpatient department with complaints of low backache, weight loss, intermittent stiffness, and fever for the past year. The patient was HLA-B27 positive, diagnosed as ankylosing spondylitis, and clinical symptoms were attributed to sacroiliitis. However, his fever and weight loss, while on treatment, were unexplained. Roentgenogram, computed tomography, and magnetic resonance imaging of the patient depicted a large bone tumor centered at the junction of the right pedicle and transverse process of L5 vertebra, associated with severe reactive marrow edema, periosteal reaction, periostitis, and sclerosis in the posterior vertebral elements also extending into the L4 vertebra. The lesion was suspected to be osteoblastoma with close imaging differential as osteosarcoma. CT-guided biopsy proved osteoblastoma with acute local toxic flare.

The bone flare phenomenon during the treatment of bone metastases of lung adenocarcinoma

Background The bone flare phenomenon, defined as an increase in bone lesion activity, is a kind of benign bone change in response to ongoing tumor treatment. The purpose of this study was to investigate the time, incidence, and clinical significance of bone flare in lung adenocarcinoma patients with bone metastases, as well as to observe the levels of serum alkaline phosphatase ALP and serum calcium Ca^2+ in patients with bone flare phenomenon.Methods Fifty-seven patients with advanced lung adenocarcinoma who participated in the anti-tumor clinical trials from December 2017 to December 2019 in Linyi Cancer Hospital were included in the study. The CT (computed tomography, CT) images, serum ALP and Ca^2+ from all patients were analyzed retrospectively.Results Among a total of 57 patients, 28 were male, and 29 were female. The median age was 62 years (33–75 years), and 30 of them had bone metastases at baseline. Forty-six EGFR negative patients received platinum-based dual-drug chemotherapy or bevacizumab or combined with PD-1 antibody inhibitors, and 11 EGFR positive patients received targeted EGFR inhibitors. The bone flare was detected in 7 out of 30 patients with bone metastases at baseline (5 patients in the combined chemotherapy group and two patients in the targeted treatment group). The incidence of bone flare was 23.33% (7 / 30). The median time was 45 days after treatment (from 41 days to 120 days), and most of them occurred in the early stages of the treatment.

The Alkaline Phosphatase Flare Phenomenon: A Transient Substantial Increase in Alkaline Phosphatase Concentration in a Prostate Cancer Patient after Starting GnRH Agonist Treatment

A 78-year-old man with metastatic prostate cancer was referred to the hospital 5 weeks after the initiation of systemic therapy with goserelin (GnRH agonist) because of a significant increase in alkaline phosphatase (ALP) concentration despite clinical improvement. Further workup revealed a decrease in prostate-specific antigen levels and a lack of radiological signs of disease progression. Subsequently, the ALP dropped spontaneously. This case report is an example for an early ALP flare after initiation of endocrine therapy in patients with bone metastasis which is consistent with a treatment response. Clinicians should be familiar with the ALP flare phenomenon in this setting, which does not reflect disease progression or treatment failure, in order to prevent unnecessary investigations, hospital admissions, or even erroneous termination of successful therapy.

Flare phenomenon in prostate cancer: recent evidence on new drugs and next generation imaging

Over the years, an increasing proportion of metastatic prostate cancer patients has been found to experience an initial bone flare phenomenon under both standard therapies (androgen deprivation therapy, chemotherapy, radiotherapy, abiraterone, enzalutamide) and novel agents (immunotherapy, bone-targeting radioisotopes). The underlying biological mechanisms of the flare phenomenon are still elusive and need further clarification, particularly in relation to different types of treatment and their treatment response assessment. Flare phenomenon is often underestimated and, in some cases, can negatively affect clinical outcome. In cases with suspected bone flare, the treatment should be continued for a minimum of 12 more weeks before further decisions about efficacy can be taken. Physicians and patients should be aware of this effect to avoid unwarranted anxiety and inadequate early discontinuation of treatment. This review aims at highlighting new evidence on flare phenomenon arising after the introduction of new drugs extending across the biochemical, radiographic and clinical spectrum of the disease.