BACKGROUND Natural killer (NK) cells have a spontaneous cytotoxic capacity against tumor cells. These cells represent a small proportion of human colon carcinoma‐infiltrating lymphocytes. Their prognostic significance in these tumors has yet to be determined. METHODS One hundred and fifty‐seven patients who each had a colectomy for large bowel adenocarcinoma were studied. No patient received adjuvant therapy. Immunohistochemical stains were performed for NK cells using the monoclonal antibody CD57. The number of NK cells was counted using a MICRON image analyzer. The total area studied for each tumor was 1 cm2. In this area, 50 intratumoral fields of 0.173 mm2 were selected. The degree of NK infiltration was classified as little (<50 NK cells), moderate (50‐150 NK cells), and extensive (>150 NK cells). The Kaplan‐Meier method was used to obtain survival figures. Multivariate analyses were performed using the Cox regression model. RESULTS At 5 years, patients with little and moderate NK infiltration showed significantly shorter survival rates (overall and disease free survival) than those with extensive infiltration (P < 0.01). Three significant factors affecting survival were selected in a stepwise fashion in increasing order as follows: TNM stage, NK infiltration, and lymphocytic infiltration. Patients with TNM Stage III disease and extensive NK infiltration showed significantly longer survival rates than those with little or moderate infiltration (P < 0.001). In these patients, multivariate analysis using the Cox regression model identified two significant variables: number of involved lymph nodes and NK cell infiltration. CONCLUSIONS In patients with colorectal carcinoma, an extensive intratumoral infiltration of NK cells is associated with a favorable tumor outcome. Intratumoral infiltration of NK cells can be used as a variable with prognostic value, especially in patients with TNM Stage III disease. Cancer 1997; 79:2320‐8. © 1997 American Cancer Society.

PURPOSE Radiation dose received by the neural stem cells of the hippocampus during whole-brain radiotherapy has been associated with neurocognitive decline. The key concern using hippocampal avoidance-prophylactic cranial irradiation (HA-PCI) in patients with small-cell lung cancer (SCLC) is the incidence of brain metastasis within the hippocampal avoidance zone. METHODS This phase III trial enrolled 150 patients with SCLC (71.3% with limited disease) to standard prophylactic cranial irradiation (PCI; 25 Gy in 10 fractions) or HA-PCI. The primary objective was the delayed free recall (DFR) on the Free and Cued Selective Reminding Test (FCSRT) at 3 months; a decrease of 3 points or greater from baseline was considered a decline. Secondary end points included other FCSRT scores, quality of life (QoL), evaluation of the incidence and location of brain metastases, and overall survival (OS). Data were recorded at baseline, and 3, 6, 12, and 24 months after PCI. RESULTS Participants' baseline characteristics were well balanced between the two groups. The median follow-up time for living patients was 40.4 months. Decline on DFR from baseline to 3 months was lower in the HA-PCI arm (5.8%) compared with the PCI arm (23.5%; odds ratio, 5; 95% CI, 1.57 to 15.86; P = .003). Analysis of all FCSRT scores showed a decline on the total recall (TR; 8.7% v 20.6%) at 3 months; DFR (11.1% v 33.3%), TR (20.3% v 38.9%), and total free recall (14.8% v 31.5%) at 6 months, and TR (14.2% v 47.6%) at 24 months. The incidence of brain metastases, OS, and QoL were not significantly different. CONCLUSION Sparing the hippocampus during PCI better preserves cognitive function in patients with SCLC. No differences were observed with regard to brain failure, OS, and QoL compared with standard PCI.

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This modality of treatment offers an alternative for those patients not candidates for surgical procedures because of medical contraindications or risk of disfigurement or functional impairment.

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Purpose/Objective(s): Clinical evidence suggests that radiation dose received by the hippocampus during whole brain radiotherapy may play a role in radiation-induced neurocognitive decline. To prospectively evaluate the neurocognitive (NC) benefit of hippocampal sparing (PCI-HA), we have developed a phase III clinical trial (PREMER) to test hippocampal sparing during PCI. Materials/Methods: 118 patients undergoing PCI were randomized to receive PCI (nZ60) or PCI-HA (nZ58). The hippocampus was contoured, and hippocampal avoidance regions were created using a 5-mm volumetric expansion around the hippocampus. Linear accelerator ebased intensitymodulated radiotherapy and Volumetric Modulated Arc Therapy treatment plans were generated for a prescription dose of 25 Gy in 10 fractions. The main objective was NC function at 3 months assessed by Free and Cued Selective Reminding Test (FCSRT). The FCSRT is a well-validated and reliable assessment of memory, including encoding, retrieval, and retention of new information over time. Results: These treatment modalities spared the hippocampus, with a D100 of 8.4 AE 2.0 Gy and a maximum dose of 14.5 AE 3.3 Gy. There was a decline in free delayed recall in PCI vs PCI-HA arm at 3 months (21.7 vs 5.1%; p 0.01; OR 5 [IC 95% 1.36-18.87]) at 6 months (32.6 vs 7.3%; p 0.008; OR 6.1 [IC 95% 1.60-23.29]) and at 12 months (18.5 vs 3.8%; p 0.09; OR 5.7 [IC 95% 0.61-52.42])

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