PET after completion of therapy should be performed at least 3 weeks, and preferably at 6 to 8 weeks, after chemotherapy or chemoimmunotherapy, and 8 to 12 weeks after radiation or chemoradiotherapy. Visual assessment alone is adequate for interpreting PET findings as positive or negative when assessing response after completion of therapy. Mediastinal blood pool activity is recommended as the reference background activity to define PET positivity for a residual mass > or = 2 cm in greatest transverse diameter, regardless of its location. A smaller residual mass or a normal sized lymph node (ie, < or = 1 x 1 cm in diameter) should be considered positive if its activity is above that of the surrounding background. Specific criteria for defining PET positivity in the liver, spleen, lung, and bone marrow are also proposed. Use of attenuation-corrected PET is strongly encouraged. Use of PET for treatment monitoring during a course of therapy should only be done in a clinical trial or as part of a prospective registry.
Radioimmunotherapy with (90)Y ibritumomab tiuxetan is well tolerated and produces statistically and clinically significant higher ORR and CR compared with rituximab alone.
• Pembrolizumab was first shown to be clinically active in CLL patients with RT.• PD-1 and PD-L1 expression in tumor microenvironment are promising biomarkers to select RT patients for PD-1 blockade.Chronic lymphocytic leukemia (CLL) patients progressed early on ibrutinib often develop Richter transformation (RT) with a short survival of about 4 months. Preclinical studies suggest that programmed death 1 (PD-1) pathway is critical to inhibit immune surveillance in CLL. This phase 2 study was designed to test the efficacy and safety of pembrolizumab, a humanized PD-1-blocking antibody, at a dose of 200 mg every 3 weeks in relapsed and transformed CLL. Twenty-five patients including 16 relapsed CLL and 9 RT (all proven diffuse large cell lymphoma) patients were enrolled, and 60% received prior ibrutinib. Objective responses were observed in 4 out of 9 RT patients (44%) and in 0 out of 16 CLL patients (0%). All responses were observed in RT patients who had progression after prior therapy with ibrutinib. After a median follow-up time of 11 months, the median overall survival in the RT cohort was 10.7 months, but was not reached in RT patients who progressed after prior ibrutinib. Treatment-related grade 3 or above adverse events were reported in 15 (60%) patients and were manageable. Analyses of pretreatment tumor specimens from available patients revealed increased expression of PD-ligand 1 (PD-L1) and a trend of increased expression in PD-1 in the tumor microenvironment in patients who had confirmed responses. Overall, pembrolizumab exhibited selective efficacy in CLL patients with RT. The results of this study are the first to demonstrate the benefit of PD-1 blockade in CLL patients with RT, and could change the landscape of therapy for RT patients if further validated. This trial was registered at www.clinicaltrials.gov as #NCT02332980. (Blood. 2017;129(26):3419-3427)
These phase I/II data demonstrate that IDEC-Y2B8 radioimmunotherapy is a safe and effective alternative for outpatient therapy of patients with relapsed or refractory NHL. A phase III study is ongoing.
Extrapulmonary poorly differentiated neuroendocrine carcinomas can originate in the gastrointestinal tract, bladder, cervix, and prostate. These high-grade malignancies are characterized by aggressive histological features (high mitotic rate, extensive necrosis, and nuclear atypia) and a poor clinical prognosis. They are infrequently associated with secretory hormonal syndromes (such as the carcinoid syndrome) and rarely express somatostatin receptors.
Most poorly differentiated neuroendocrine carcinomas are locally advanced or metastatic at presentation. First-line systemic chemotherapy with a platinum agent (cisplatin or carboplatin) and etoposide is recommended for most patients with metastatic-stage disease; however, response durations are often short. Sequential or concurrent chemoradiation is recommended for patients with loco-regional disease. In patients with localized tumors undergoing surgical resection, adjuvant treatment (chemotherapy with or without radiation) is warranted in most cases.
Neuroendocrine tumors (NETs) of the distal colon and rectum are also known as hindgut carcinoids based on their common embryologic derivation. Their annual incidence in the United States is rising, primarily as a result of increased incidental detection. Symptoms of rectal NETs include hematochezia, pain, and change in bowel habits. Most rectal NETs are small, submucosal in location, and associated with a very low malignant potential. Tumors larger than 2 cm or those invading the muscularis propria are associated with a significantly higher risk of metastatic spread. Colonic NETs proximal to the rectum are rarer and tend to behave more aggressively. The incidence of rectal NETs in African Americans and Asians is substantially higher than in Caucasians. Colorectal NETs are generally not associated with a hormonal syndrome such as flushing or diarrhea. A multidisciplinary approach is recommended in diagnosing and managing hindgut NETs.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.