Is elective nodal irradiation beneficial in patients with pathologically negative lymph nodes after neoadjuvant chemotherapy and breast-conserving surgery for clinical stage II-III breast cancer? A multicentre retrospective study (KROG 12-05).

BACKGROUND: To evaluate the effects of elective nodal irradiation (ENI) in clinical stage II-III breast cancer patients with pathologically negative lymph nodes (LNs) (ypN0) after neoadjuvant chemotherapy (NAC) followed by breast-conserving surgery (BCS) and radiotherapy (RT). METHODS: We retrospectively analysed 260 patients with ypN0 who received NAC followed by BCS and RT. Elective nodal irradiation was delivered to 136 (52.3%) patients. The effects of ENI on survival outcomes were evaluated. RESULTS: After a median follow-up period of 66.2 months (range, 15.6-127.4 months), 26 patients (10.0%) developed disease recurrence. The 5-year locoregional recurrence-free survival and disease-free survival (DFS) for all patients were 95.5% and 90.5%, respectively. Pathologic T classification (0-is vs 1 vs 2-4) and the number of LNs sampled (<13 vs ≥13) were associated with DFS (P=0.0086 and 0.0012, respectively). There was no significant difference in survival outcomes according to ENI. Elective nodal irradiation also did not affect survival outcomes in any of the subgroups according to pathologic T classification or the number of LNs sampled. CONCLUSIONS: ENI may be omitted in patients with ypN0 breast cancer after NAC and BCS. But until the results of the randomised trials are available, patients should be put on these trials.

Stage IE/IIE extranodal NK/T-cell lymphoma arising in the nasal cavity: analysis of CT findings and their prognostic value.

AIM: To investigate the computed tomography (CT) findings in patients with stage IE/IIE extranodal natural killer/T-cell lymphoma (ENKTL) arising in the nasal cavity and to evaluate whether imaging findings revealed by CT have prognostic value. MATERIALS AND METHODS: The CT findings of 62 patients diagnosed with IE/IIE ENKTL arising in the nasal cavity were retrospectively reviewed. Imaging findings were investigated, and evaluated imaging findings were analysed for the prognostic value of overall survival (OS) and disease-free survival (DFS). RESULTS: Of the 62 patients, 21 (34%) presented with a superficial infiltrative, 38 (61%) with a mass forming, and three (5%) with a combined pattern. Of all imaging findings, local invasiveness (n = 26, 42%), including bony destruction, erosion, or soft-tissue involvement, was the only independent prognostic factor for OS [p = 0.008; hazard ratio (HR): 3.85; 95% confidence intervals (CI): 1.42-10.44] and DFS (p = 0.001; HR: 4.25; 95% CI: 1.72-10.47). In a subgroup analysis of 36 cases with no local invasiveness, a superficial infiltrative pattern in one nasal cavity was a positive prognostic factor for OS (p = 0.028) and DFS (p = 0.008). CONCLUSION: Imaging findings at CT provided clinically useful predictions for treatment outcomes. Local invasiveness revealed by CT findings was a strong prognostic factor for poor OS and DFS. In addition, in patients with no local invasiveness, a superficial infiltrative pattern in one nasal cavity predicted favourable OS and DFS.

Treatment results of post-operative radiotherapy in patients with salivary duct carcinoma of the major salivary glands.

OBJECTIVE: Salivary duct carcinoma (SDC) is a rare malignancy of high-grade pathological type. We evaluated clinical outcomes and prognostic factors in 35 patients with SDC treated post-operatively with adjuvant radiation. METHODS: We retrospectively assessed overall survival, locoregional control and disease-free survival in 35 patients with SDC of the major salivary glands who underwent surgery and were subsequently treated with radiotherapy. The evaluated prognostic factors included gender, age, symptom duration, tumour site, tumour size, TNM classification, and the following pathological features: perineural invasion, lymphovascular invasion, extraparenchymal invasion and resection-margin status. RESULTS: Of the 35 patients, 30 (85.7%) were male. Median age at initial diagnosis was 62 years (range 38-75 years). The parotid gland was the main site affected in 22 patients (62.9%). 18 patients (51.5%) had pathological T3/T4 tumours, and 26 (74.3%) showed pathological nodal involvement. Actuarial 5-year locoregional control, disease-free survival and overall survival rates were 63.3%, 47.4% and 55.1%, respectively. The cause-specific death rate was 31.4% (n=11). Pathological nodal involvement was correlated with distant metastasis (p=0.011). Lymphovascular invasion was significantly prognostic for distant metastasis-free survival (p=0.049), locoregional control (p=0.012) and overall survival (p=0.003) in a Cox proportional hazard model, whereas perineural invasion was only significantly prognostic for overall survival (p=0.005). CONCLUSIONS: Surgery and post-operative radiotherapy were effective for locoregional control. Lymphovascular invasion and perineural invasion were significant prognostic factors in patients with SDC.

Recombinant human epidermal growth factor treatment of radiation-induced severe oral mucositis in patients with head and neck malignancies.

Mucositis of the oral cavity and pharynx is a major dose-limiting factor in the application of radiotherapy (RT) to patients with head and neck cancer. Therefore, we evaluated the wound healing effect of human recombinant epidermal growth factor (rhEGF) in head and neck cancer and lymphoma patients with irradiation (with or without combined chemotherapy-induced oral mucositis). Patients at Asan Medical Center who had undergone definitive RT of the head and neck region with or without combined chemotherapy and who had developed severe oral mucositis (higher than the Radiation Therapy Oncology Group grade 3) were treated with topical rhEGF twice daily for 7 days. The evaluation of response with regard to oral mucositis was performed 1 week later. Of the 11 treated patients, three had nasopharyngeal carcinoma, three had carcinoma of the oropharynx, two had carcinoma of the oral cavity, one had carcinoma of the hypopharynx and two had lymphoma of the head and neck. Six patients received RT only, and five patients received concurrent chemoradiotherapy. All patients showed improvements in their oral mucositis after topical treatment with rhEGF in that the Radiation Therapy Oncology Group grade was significantly decreased (P = 0.0000). This finding suggests that rhEGF is effective and safe for the treatment of radiation-induced mucositis. Further studies are needed to determine the optimal dosage and fractionation schedule.

Effect of protein kinase C inhibitor (PKCI) on radiation sensitivity and c-fos transcription.

PURPOSE: The human genetic disorder ataxia-telangiectasia (AT) is a multisystem disease characterized by extreme radiosensitivity. Although ionizing radiation was known to induce c-fos transcription and cellular protein kinase C (PKC) induces the expression of this immediate response gene, little is known about how mutated AT (ATM) or PKC-mediated signal transduction pathway modulates the c-fos gene transcription and gene expression. Here we have studied the effect of PKC inhibitor (PKCI) on radiation sensitivity and c-fos transcription in normal and AT cells, and also studied whether PKCI effect on c-fos occurs in Ras-dependent pathway. METHODS AND MATERIALS: Normal (LM217) and AT (AT5BIVA) cells were transfected with PKCI expression plasmid and integration and overexpression of PKCI was evaluated by polymerase chain reaction and northern blotting, respectively. Cells were irradiated at a dose of 5 Gy/min with 137Cs irradiator and harvested 48 h after irradiation and investigated apoptosis with TUNEL method. The c-fos transcription activity was studied by performing compute assisted tomography (CAT) assay of reporter gene after transfection of c-fos CAT plasmid into LM and AT cells. Overexpression of Ras protein in transfected cells was shown by western blotting. RESULTS: Our results demonstrated for the first time a role of PKCI on the radiation sensitivity and c-fos transcription in LM and AT cells. PKCI increased radiation induced apoptosis in LM cells (5% to 20%) but reduced apoptosis slightly in AT cells. The basal c-fos transcription activity is 70 times lower in AT cells than in LM cells. This c-fos transcription activity was repressed by overexpression of PKCI in LM cells but not in AT cells. After induction of c-fos by Ras protein, overexpression of PKCI repressed c-fos transcription in LM cells but not in AT cells. CONCLUSIONS: Overexpression of PKCI increased radiation sensitivity and repressed c-fos transcription in LM cells but not in AT cells, and this is related with Ras. These results suggest that the effect of PKCI on c-fos transcription activity is related with Ras dependent signal transduction pathways and these mechanisms are different between normal fibroblasts, LM and ATM mutated, AT cells. The data obtained by this study provided evidence for novel transcriptional difference between LM and AT cells and this may be a reason for increased radiation sensitivity of AT cells.