Impact of incidental irradiation on clinically uninvolved nodal regions in patients with advanced non-small-cell lung cancer treated with involved-field radiation therapy: does incidental irradiation contribute to the low incidence of elective nodal failure?

PURPOSE: To evaluate the incidental irradiation dose to elective nodal regions in the treatment of advanced non-small-cell lung cancer with involved-field radiation therapy (IF-RT) and the pattern of elective nodal failure (ENF). METHODS AND MATERIALS: Fifty patients with advanced non-small-cell lung cancer, who received IF-RT at Kagawa University were enrolled. To evaluate the dose of incidental irradiation, we delineated nodal regions with a Japanese map and the American Thoracic Society map (levels 1-11) in each patient retrospectively and calculated the dose parameters such as mean dose, D95, and V95 (40 Gy as the prescribed dose of elective nodal irradiation). RESULTS: Using the Japanese map, the median mean dose was more than 40 Gy in most of the nodal regions, except at levels 1, 3, and 7. In particular, each dosimetric parameter of level 1 was significantly lower than those at other levels, and each dosimetric parameter of levels 10 to 11 ipsilateral (11I) was significantly higher than those in other nodal regions. Using the American Thoracic Society map, basically, the results were similar to those of the Japanese map. ENF was observed in 4 patients (8%), five nodal regions, and no mean dose to the nodal region exceeded 40 Gy. On the Japanese map, each parameter of these five nodal region was significantly lower than those of the other nodal regions. CONCLUSIONS: These results show that a high dose of incidental irradiation may contribute to the low incidence of ENF in patients who have received IF-RT.

Unknown primary carcinoma, diagnosed as inflammatory breast cancer,and successfully treated with trastuzumab and vinorelbine.

Occult breast cancer presenting with axillary lymph node metastases is uncommon, and inflammatory breast cancer (IBC), as a subtype, is quite rare. Here we describe a case of IBC, which arose as an unknown primary carcinoma; the patient presented with axillary lymph node metastasis, and was successfully treated with trastuzumab and vinorelbine. Specifically, a 55-year-old woman presented with right axillary lymphadenopathy. Although she underwent various examinations, the primary site of the disease was not revealed. Axillary lymph node dissection was performed, and the lesion was diagnosed as a poorly differentiated adenocarcinoma. The patient chose to be treated by alternative medicine. About 6 months later, she was referred to our hospital, due to marked bilateral neck and axillary lymph node swelling. She presented with diffuse right breast enlargement, redness, and peau d'orange. Computed tomography (CT) of the breast showed skin thickening and swelling of the right breast.F-18 Fluorodeoxyglucose positron emission tomography (FDG-PET) showed FDG uptake in the right breast. The patient was clinically diagnosed with IBC. Because overexpression of the human epidermal growth factor receptor 2 (HER2) was found in the specimen from her right axillary lymph node, she was treated with trastuzumab and vinorelbine. Two months after the start of chemotherapy, CT revealed a complete response in the lymph nodes, and the skin thickening and parenchymal edema of the right breast had improved. FDG-PET was also performed at this time, and revealed no FDG uptake in either the right breast or the lymph nodes.

[Hyperfractionated radiotherapy with concurrent chemotherapy for advanced esophageal cancer].

The clinical efficacy and safety of hyperfractionated radiotherapy with concurrent chemotherapy were studied retrospectively in patients with primary advanced esophageal cancer. The subjects were 31 patients who were treated with hyperfractionated radiotherapy and concurrent chemotherapy in our institution between 1990 and 2001. The chemoradiotherapy consisted of cisplatin 70-80 mg/m2 on day one, and continuous infusion of 5-fluorouracil 700-800 mg/m2/24 hours on days 1 to 3, with concurrent hyperfractionated radiotherapy (57.6-72 Gy). Complete remission (CR) was observed in 17 cases, and partial response in 13 cases (response rate: 96. 7%). Three-year survival rate and 5-year survival rate were 35.5% and 26.3%, respectively. Grade 3/4 hematological toxicities included leukocytes in 7 patients (22.6%), hemoglobin in 6 patients (19.4%), and platelets in 4 patients (12.9%). Grade 3 dysphagia-esophageal related to radiation was observed in 3 patients (9.7%). Late toxicities occurred with the following incidences: hypothyroidism in 2 patients, benign esophageal strictures in 2 patients, pericardial effusion in 8 patients, and pleural effusion in 8 patients. The results suggest that combined chemotherapy and hyperfractionated radiotherapy is an effective and well-tolerated regimen.

Usefulness of FDG-PET imaging for the radiotherapy treatment planning of pyothorax-associated lymphoma.

Pyothorax-associated lymphoma (PAL) is a non-Hodgkin's lymphoma developing in the pleural cavity after a long-standing history of chronic pyothorax (CP). F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) imaging is a useful modality for determination of disease extent of various malignant tumors, including malignant lymphoma, but there have been no reports describing the usefulness of FDG-PET imaging in PAL. Here we report a case of PAL that relapsed after chemotherapy and was successfully treated by radiotherapy. FDG-PET imaging revealed that the tumor was localized to a soft-tissue attenuation mass behind the CP cavity in the right thorax, but did not infiltrate the CP cavity. A total dose of 40 Gy was administered to the area that included the PET-positive lesion, instead of including the entire CP cavity in the radiation field. Although computed tomography (CT) showed a residual mass, no FDG uptake was indicated by FDG-PET imaging performed just after the end of radiotherapy, and additional irradiation was not performed. No sign of relapse was found by FDG-PET imaging 3 months later. FDG-PET imaging was useful for both the planning of radiotherapy and assessing the treatment response of PAL.

[Three dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer under field adjustment with implanted gold markers: early clinical outcome].

Three dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer under field adjustment with gold marker implantation was performed according to the treatment strategy based on the clinical risk factors to the patients who chose external beam radiotherapy. The treatment strategy contains indications for laparoscopic staging lymphadenectomy and neoadjuvant combined androgen blockade (CAB). This protocol was applied to 19 patients at Kagawa University Hospital from July 2001 to December 2003. The patients were divided into high-risk group (n=14): T3-4N0M0 or PSA > or = 20 ng/ml or Gleason sum > or = 8 or suspicious node, and low-risk group (n=5): T1c-2bN0M0 and PSA < 20 ng/ml and Gleason sum < or = 7 and no suspicious nodes. Basically, high-risk patients underwent laparoscopic staging lymphadenectomy prior to radiotherapy. One of the 14 patients had a positive node and underwent endocrine therapy. The high-risk group received neoadjuvant CAB for 3 to 4 months, followed by gold marker implantation. One patient chose endocrine therapy at this point. Low-risk patients underwent marker implantation without endocrine therapy. Every patient successfully completed planned irradiation. The changes of prostate volume and serum PSA after neoadjuvant CAB were significant [28.7 ml to 15.7 ml (p=0.004) and 53.9 ng/ml to 1.4 ng/ml (p=0.023), respectively]. Only one patient in the high-risk group had biochemical failure. No grade 3 or 4 adverse events occurred in NCI-CTC grading. The analysis of gravity center migration of the implanted gold markers in the first 8 patients showed that the planned safety margin might not be wide enough to avoid neighboring organ irradiation. These results suggested that 3D-CRT under field adjustment with implanted gold markers contributes to both higher efficacy and lower morbidity.

Selective eosinophil adhesion to fibroblast via IFN-gamma-induced galectin-9.

Among galectin family members, galectin-9 was first described as a potent eosinophil chemoattractant derived from Ag-stimulated T cells. In the present study a role of galectin-9 in the interaction between eosinophils and fibroblasts was investigated using a human lung fibroblast cell line, HFL-1. RT-PCR, real-time PCR, and Western blot analyses revealed that both galectin-9 mRNA and protein in HFL-1 cells were up-regulated by IFN-gamma stimulation. On the one hand, IL-4, known as a Th2 cytokine, did not affect the galectin-9 expression in HFL-1 cells. We further confirmed that IFN-gamma up-regulated the expression of galectin-9 in primary human dermal fibroblasts. Flow cytometric analysis revealed that IFN-gamma up-regulated surface galectin-9 expression on HFL-1 cells. Stimulation of HFL-1 cells with IFN-gamma up-regulated adhesion of eosinophils, but not neutrophils, to HFL-1 cells. This adherence of eosinophils to HFL-1 cells was inhibited by both lactose and anti-galectin-9 Ab. These findings demonstrate that IFN-gamma-induced galectin-9 expression in fibroblasts mediates eosinophil adhesion to the cells, suggesting a crucial role of galectin-9 in IFN-gamma-stimulated fibroblasts as a physiological modulator at the inflammatory sites.