ABSTRACT
Radiation-induced immune-mediated abscopal effects (AE) of conventional radiotherapy are very rare. Whole-tumor irradiation leads to lymphopenia due to killing of immune cells in the tumor microenvironment, resulting in immunosuppression and weak abscopal potential. This limitation may be overcome by partial tumor irradiation sparing the peritumoral immune-environment, and consequent shifting of immune-suppressive to immune-stimulatory effect. This would improve the radiation-directed tumor cell killing, adding to it a component of immune-mediated killing. Our preclinical findings showed that the high-single-dose irradiation of hypoxic tumor cells generates a stronger bystander effect (BE) and AE than the normoxic cells, suggesting their higher "immunogenic potential". This led to the development of a novel Stereotactic Body RadioTherapy (SBRT)-based PArtial Tumor irradiation targeting HYpoxic segment (SBRT-PATHY) for induction of the immune-mediated BE and AE. Encouraging SBRT-PATHY-clinical outcomes, together with immunohistochemical and gene-expression analyses of surgically removed abscopal-tumor sites, suggested that delivery of the high-dose radiation to the partial (hypoxic) tumor volume, with optimal timing based on the homeostatic fluctuation of the immune response and sparing the peritumoral immune-environment, would significantly enhance the immune-mediated anti-tumor effects. This review discusses the current evidence on the safety and efficacy of SBRT-PATHY in the treatment of unresectable hypoxic bulky tumors and its bystander and abscopal immunomodulatory potential.
ABSTRACT
OBJECTIVE: To evaluate the diagnostic accuracy of a modified scrape cell block (SCB) technique in a large series of patients. The technique was especially developed and tested for fine-needle aspiration of thyroid and parathyroid nodules. STUDY DESIGN: Eighty-two ultrasound-guided fine-needle aspiration specimens with the sonographic aspect of a thyroid (n = 33) or a possible parathyroid nodule (n = 49) were studied. Immunohistochemistry (IHC) was used on cell blocks containing plasma, thromboplastin, and selected 3-dimensional cell aggregates scraped off Papanicolaou-stained smears. Antibodies for chromogranin A, thyroglobulin, parathyroid hormone, calcitonin, and carcinoembryonic antibody (CEA) were used. In cases of reduced immunosensitivity or suspected metastases or rare primary tumors, additional IHC markers were employed. RESULTS: Chromogranin A was expressed in all 28 parathyroid adenomas (PA), in 7 of 8 hyperplastic parathyroid glands, and in 13 of 14 medullary thyroid carcinomas (MTC). When combining positivity for chromogranin A and calcitonin/CEA, the specificity for the detection of MTC was 100%. Parathyroid hormone was expressed in 26 of 36 parathyroid nodules (72.2%). When combining follicular microarchitecture and expression of chromogranin A, the specificity for the detection of parathyroid tissue was 97%. CONCLUSION: With the modified SCB technique, accurate cytological diagnoses were obtained in 97.6% of 82 patients.
