Primary testicular diffuse large B-cell lymphoma (PT-DLBCL) is a unique subtype of DLBCL. The impact of rituximab on survival and patterns of treatment failure in PT-DLBCL patient remain controversial. We analyzed the clinical and biological feature of 280 PT-DLBCL cases, 64% of which were treated with rituximab-containing regimens. Although most (95%) patients achieved complete remission, a continuous risk of relapse was observed. Rituximab significantly reduced the cumulative risk of relapse (P=0.022) and improved both progression-free survival (PFS, P=0.012) and overall survival (OS, P=0.027) of PT-DLBCL patients (5-year PFS, 56% vs 36%; 5-year OS, 68% vs 48%). Central nervous system and contralateral testis were the most common sites of relapse, but other extranodal and nodal sites of relapse were also observed. Most cases of PT-DLBCL had a non-germinal center B-cell like (84%) immunophenotype and an activated B-cell like (86%) gene expression profile (GEP) subtype. The distinctive GEP signature of primary testicular lymphoma was relevant to tumor cell proliferation, dysregulated expression of adhesion molecules and immune response, likely accounting for the poor outcome. Accordingly, forkhead box P1 transcription factor (FOXP1) and T-cell leukemia/lymphoma 1 (TCL1) oncogenic activation were confirmed and predicted a significant trend of poor survival. This study provides valuable observations for better understanding of both clinical and biological features in PT-DLBCL patients.

X-ray repair cross-complementing 1 (XRCC1) plays a key role in DNA base excision repair and cells lacking its activity are hypersensitive to DNA damage. Recently, we reported a SNP (rs3213245, À77T>C) in the XRCC1 gene 5 0 untranslated region (UTR) was significantly associated with the risk of developing esophageal squamous-cell carcinoma. Computer analysis predicted that this SNP was in the core of Sp1-binding motif, which suggested its functional significance. Gel shift and super shift assays confirmed that À77T>C polymorphic site in the XRCC1 promoter was within the Sp1-binding motif and the T>C substitution greatly enhanced the binding affinity of Sp1 to this region. Luciferase assays indicated that the Sp1-high-affinity C-allelic XRCC1 promoter was associated with a reduced transcriptional activity. The association between À77T>C and three other amino-acid substitution-causing polymorphisms in XRCC1 and risk of lung cancer was examined in 1024 patients and 1118 controls and the results showed that only the À77T>C polymorphism was significantly associated with an increased risk of developing lung cancer. Multivariate logistic regression analysis found that an increased risk of lung cancer was associated with the variant XRCC1 À77 genotypes (TC and CC) compared with the TT genotype (OR ¼ 1.46, 95% CI ¼ 1.18-1.82; P ¼ 0.001) and the increased risk was more pronounced in smokers (OR ¼ 1.63, 95% CI ¼ 1.20-2.21) than in non-smokers (OR ¼ 1.28, 95% CI ¼ 0.94-1.76). Taken together, these results showed that the functional SNP À77T>C in XRCC1 5 0 UTR was associated with cancer development owing to the decreased transcriptional activity of C-allelecontaining promoter with higher affinity to Sp1 binding.

This study revealed novel genetic variants in SMGs associated with lung cancer risk, which might contribute to elucidating the biological network involved in lung cancer development.

Purpose: To evaluate the performance of an automatic CT‐to‐CT image registration algorithm for both soft tissue and bony targets. Method and Materials: CT‐Assisted Targeting (CAT) software was developed for on‐line CT‐guided radiotherapy using a CT‐on‐rails system. The algorithm was tested in two phantom studies and cross‐compared with other radiotherapy imaging techniques available in the same room. A BAT phantom (North American Scientific, Chatsworth) was intentionally shifted and imaged each time by (1) an electronic portal imaging device, (2) ultrasound, and (3) the CT‐on‐rails. A Rando pelvic phantom with imbedded gold markers for target localization using the ACCULOC™ software (Northwest Medical Physics Equipment) was also used. To test the software in patient images, 15 prostate cancer patients receiving 3 CT scans per week over 8 week's treatment were selected. The prostate was chosen as the soft tissue target and a bony structure in the pelvic region (excluding the femoral heads) was used as the bony alignment target. A total of 366 treatment‐day CT images were registered using the CAT software and verified by a single observer. Results: The phantom studies demonstrated that the CAT software can achieve sub‐millimeter accuracy in detecting the intended shifts and were generally agreed well with other established imaging modalities in this controlled phantom study. The CAT software also performed well in patient's CT images. The failure rate, as defined by greater than 3 mm differences between the automatic detected positions and the final positions adjusted by the human observer, was only 2.1 % for soft tissue target registration and 1.6% for bony target registration in 366 CT images. The automatic registration takes less than 12 seconds. Conclusion: We have designed a highly robust, accurate, and fast computer algorithm for CT‐to‐CT image registration. The software provides a quick and reliable application for CT‐guided radiotherapy.

Conclusion: The primary tumor is the most common site of progression in patients with metastatic EGFR-mt NSCLC on a TKI. In 15% of patients, progression was limited to the primary site in the lung. Interestingly, patients with liver metastases have a higher incidence of primary site progression, warranting further evaluation. Additionally, FFP is improved in patients who have undergone upfront treatment to the primary site, regardless of modality, although this finding may be affected by selection bias. These findings will help inform treatment paradigms investigating local therapy in metastatic EGFR-mt NSCLC, including patients presenting with stage IV disease who ordinarily might not have definitive treatment to the primary site.