As expected, consistently favourable efficacy was observed in patients with KRAS WT versus MT tumours receiving first-line panitumumab plus FOLFIRI treatment.
Chemical castration improves responses to radiotherapy in prostate cancer, but the mechanism is unknown. We hypothesized that this radiosensitization is caused by castration-mediated down-regulation of nonhomologous end joining (NHEJ) repair of DNA double-strand breaks (DSBs). To test this, we enrolled 48 patients with localized prostate cancer in two arms of the study: either radiotherapy first or radiotherapy after neoadjuvant castration treatment. We biopsied patients at diagnosis and before and after castration and radiotherapy treatments to monitor androgen receptor, NHEJ, and DSB repair in verified cancer tissue. We show that patients receiving neoadjuvant castration treatment before radiotherapy had reduced amounts of the NHEJ protein Ku70, impaired radiotherapy-induced NHEJ activity, and higher amounts of unrepaired DSBs, measured by γ-H2AX foci in cancer tissues. This study demonstrates that chemical castration impairs NHEJ activity in prostate cancer tissue, explaining the improved response of patients with prostate cancer to radiotherapy after chemical castration.
Background: Adjuvant chemotherapy for stage II and III rectal cancer patients is a matter of discussion. The aim of the present study was to evaluate the prognostic value of lymphovascular (LVI) and perineural (PNI) invasion in stage II rectal cancer on a national level. Materials and methods: Clinico-pathological factors associated with disease-free survival (DFS) and time to recurrence in stage II rectal cancer patients were analyzed from patient data registered in the Swedish Colorectal Cancer Registry between 2006 and 2012. Results: Of 2649 patients with TNM stage II disease, 1395 (53%) received preoperative radiotherapy and 456 (17%) preoperative chemoradiotherapy. LVI and PNI were detected in 387 (15%) and 269 (10%) patients, respectively. Adjuvant chemotherapy was planned in 14%, but more often if LVI or PNI was detected (25% and 31%, respectively, p < .001 for both). The three-year DFS and time to recurrence were 78% and 17%, respectively. Both LVI and PNI indicated worse outcome. In patients not receiving postoperative chemotherapy, the risks of recurrence after three years were 20% if LVI was seen and 22% if PNI was detected (p < .001 for both). In the absence of LVI and PNI, it was 13% and 12%, respectively. In a multivariate Cox regression analysis, patients with LVI (hazard ratio 1.44, 95% CI 1.09-1.90; p ¼ .011) and PNI (hazard ratio 1.80, 95% CI 1.34-2.43, p < .001) had significantly increased risks of recurrence. Conclusions: Stage II rectal cancer patients with LVI and PNI have an increased risk of recurrence which emphasizes the need to properly evaluate the role of adjuvant chemotherapy particularly in these subgroups.
It is possible to visualize urinary bladder tumours larger than 1 cm in diameter with PET using (11)C-methionine, but the value of the method in the staging of the lesions is not superior to conventional methods.
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