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The postoperative hypofractionated intensity-modulated radiation therapy (POHIM-RT) trial is a phase II study to evaluate toxicity following hypofractionated intensity modulated radiation therapy (IMRT) for cervical cancer. This study describes the results of a benchmark procedure for RT quality assurance of the POHIM-RT trial. Six participating institutions were provided computed tomography for RT planning and an IMRT plan for a sample and were instructed to delineate volumes, create a treatment plan and quality assurance (QA) plan, and submit the results of all procedures. The inter-institutional agreements on RT volume and plan results were evaluated using the kappa value and dice similarity coefficients. The simultaneous truth and performance level estimation (STAPLE) method was employed to generate a consensus target volume. The treatment volumes, organs-at-risk volumes, and results of the RT plan and QA reported by the institutions were acceptable and adhered well to the protocol. In terms of clinical target volume (CTV) delineation, there were differences between the institutions, particularly in vaginal cuff and paracolpium subsites. Consensus CTV was generated from the collected CTVs with the STAPLE method. The participating institutions showed considerable agreement regarding volume, dose and QA results. To improve CTV agreement in CTV, we provided feedback with images of the consensus target volume and detailed written guidelines for specific subsites that were the most heterogeneous. [ABSTRACT FROM AUTHOR]

The optimal protocol for thoracic radiotherapy (TRT) in combination with chemotherapy in patients with limited-stage small-cell lung cancer (LS-SCLC) remains elusive. The present study aimed to evaluate radiation parameters in association with survival outcomes. A total of 101 patients with LS-SCLC who completed TRT at ≥45 Gy and concurrent chemotherapy were retrospectively reviewed. The median dose and duration of TRT were 50 Gy and 38 days, respectively. The median duration from the start of either therapy to the end of TRT (SER) was 60 days. The median survival for all patients was 26.9 months. The 3-year local control (LC), progression-free survival (PFS) and overall survival (OS) rates were 52.0, 29.5 and 37.6%, respectively, and the 5-year LC, PFS and OS rates were 50.1, 28.3 and 26.7%, respectively. Univariate analysis revealed that patient age, tumor stage, timing and dose of TRT, SER, prophylactic cranial irradiation (PCI), and tumor response were significantly associated with treatment outcomes. Multivariate analysis revealed that stage was the only significant prognostic factor for LC (P=0.011), PFS (P<0.001) and OS (P<0.001). Tumor response (P=0.014), PCI (P=0.007) and SER (P=0.005) were significant predictors of OS. OS was improved in patients who achieved complete response, and their SER was ≤70 days (P<0.001). Short treatment duration (SER ≤70 days) was a significant predictor of OS in patients with LS-SCLC who completed planned TRT at ≥45 Gy with concurrent chemoradiotherapy. [ABSTRACT FROM AUTHOR]

We evaluated the metabolic response of lymph nodes (LNs) using consecutive 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) and correlated the metabolic response with the volumetric response measured by consecutive CT.Twenty-two patients with cervical cancer that had positive LNs underwent preradiotherapy (pre-RT) and inter-RT PET/CT. The metabolic response of the LNs was assessed quantitatively and semiquantitatively by measurement of the maximal standardized uptake value. All patients underwent inter-RT CT simulation after 45 Gy to the whole pelvis and inter-RT PET/CT scans after median 63 Gy to the gross LNs.A total of 48 pelvic and para-aortic LNs were found on the pre-RT PET/CT. The mean maximal standardized uptake value of nodal disease decreased from the pre-RT of 5.2 (SD, 3.1; range, 1.8-15.6) to the inter-RT of 1.1 (SD, 2.1; range, 0-11.1). Classifying the metabolic response of all 48 nodal lesions on the inter-RT PET/CT, 38 had a complete metabolic response. The initial volume of LNs had no correlation with the metabolic response (r = 0.194, P = 0.186). The metabolic response between the pre-RT PET/CT and inter-RT PET/CT was significantly associated with the volume response between the pre-RT CT and inter-RT CT (r = 0.314, P < 0.05). However, 18 (38%) LNs showed discrepancy between metabolic response and residual LN volume. Six (27%) patients had modified RT during treatment based on inter-RT PET/CT.We suggest that the PET/CT can be a useful tool for the evaluation of the interim response of the LNs and aid in selecting patients that need further treatment. The results showed a significant correlation between the metabolic and volumetric responses during RT, although the anatomical changes of LNs would not always represent the metabolic status. [ABSTRACT FROM AUTHOR]

Purpose: We designed the Korean Radiation Oncology Group 09-03 phase III clinical trial to compare accelerated hypofractionated radiation therapy (RT) using a concomitant boost to the gross tumor volume (GTV) with conventionally fractionated 60-Gy RT in patients with stage III unresectable non-small cell lung cancer (NSCLC).Methods and Materials: A conventionally fractionated RT group (arm 1; 124 patients) received a 2-Gy daily dose to a total cumulative dose of 44 Gy to the planning target volume (PTV) in 22 fractions and 60 Gy to the GTV in 30 fractions over 6 weeks. A hypofractionated RT group (arm 2; 142 patients) received a 1.8-Gy daily dose to the PTV with a synchronous boost of 0.6 Gy to the GTV, for total cumulative doses of 45 Gy to the PTV and 60 Gy to the GTV in 25 fractions over 5 weeks. All patients received concurrent weekly chemotherapy consisting of paclitaxel and cisplatin.Results: The objective response rate of all patients was 86.5% (arm 1, 84.6%; arm 2, 88.1%; P = .612). The median overall survival was 26 months (arm 1, 26 months; arm 2, 27 months; P = .508). The median progression-free survival was 11 months (arm 1, 10 months; arm 2, 13 months; P = .295). The local tumor control rates at 2 and 5 years were 58.3% and 50.7%, respectively (arm 1, 62.4% and 51.0%, respectively; arm 2, 54.0% and 48.6%, respectively; P = .615). There were no significant between-group differences in the cumulative incidence of grade ≥3 radiation pneumonitis (P = .134) or radiation esophagitis (P = .539).Conclusions: This clinical trial did not confirm the superiority of accelerated 2.4-Gy hypofractionated RT compared with conventional 2-Gy fractionation in patients with unresectable stage III NSCLC undergoing concurrent chemoradiation therapy. [ABSTRACT FROM AUTHOR]

Background and purpose The efficacy of prophylactic extended-field irradiation (EFI) plus concomitant cisplatin in patients with locally advanced uterine cervical cancer (LAUCC) is unknown, nor is it known whether tumor carbonic anhydrase IX (CA9) expression level, a hypoxia marker, influences survival outcome. Material and methods We recruited patients with UCC, FIGO stage IB1 with pelvic lymph node (LN) metastases to IVA with negative para-aortic LN on PET/CT. CA9 expression was examined and patients were randomized to either EFI or pelvic only radiotherapy (PRT) in each CA9 group. The primary outcomes were para-aortic recurrence-free survival (PARFS) and disease-free survival (DFS). Results Between 2006 and 2011, 79 patients with CA9-positive and 37 with CA9-negative tumors were enrolled, respectively. The median follow-up period was 69.2 months (range 6.8–102.1). For CA9-positive patients, 5-year PARFS was 100% and 81.7% for those receiving EFI and PRT ( p = 0.007), respectively. DFS was 78.6% for EFI and 71.3% for PRT patients ( p = 0.353). For CA9-negative patients, 5y PARFS was 100% and 94.1% for EFI and PRT ( p = 0.317), respectively. DFS was 100% for EFI and 70.7% for PRT ( p = 0.018). Conclusion EFI significantly reduced recurrences in PAN in patients with CA9-positive tumors, but survival outcome was not improved, due to high local recurrence and high distant metastases rates. This study indicates the necessity for new therapeutic strategies for LAUCC patients whose tumors show high CA9 expression. [ABSTRACT FROM AUTHOR]

Purpose: We investigated whether adoptive cell therapy with ex vivo-activated natural killer (NK) cells enhances the therapeutic efficacy of local tumor radiation therapy (RT) using a human triple-negative breast cancer xenograft model.Methods and Materials: NK cells from healthy donors were expanded ex vivo. MDA-MB-231/Luc-GFP cells were subcutaneously implanted into the thighs of NSG mice. The animals were divided into 4 experimental groups: control, RT, NK, and RT + NK. On day 17 after tumor implantation, tumors from the RT groups were irradiated. The ex vivo-expanded NK cells were intravenously administered twice, on days 17 and 19. Primary and secondary tumors were evaluated using long-term bioluminescence imaging, and histopathology was performed on resected tumor tissue specimens.Results: The luciferase signals of the primary tumors in the RT + NK group were significantly lower than those of comparably sized primary tumors in the RT group. The long-term migration and infiltration of NK cells into the primary tumor sites were significantly higher in RT + NK than in NK mice. Moreover, lymphatic metastasis to the axillary lymph nodes and liver and lung metastases were highly suppressed in the RT + NK group, as demonstrated by BLI and p53 immunohistochemistry. The long-term survival of the RT + NK group was significantly higher than that of the RT or NK groups.Conclusions: Reduction in tumor burden by combining RT and systemic NK cell therapy improved the suppression of primary tumor growth, with efficient NK cell migration and penetration into the primary tumor site. Administered NK cells were maintained in the primary tissue for a significantly longer time in RT + NK group compared with NK group. Both lymphatic spread and distant metastasis to the lungs and liver were effectively suppressed by the combined therapy. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) with curative intent in patients with stage IVB cervical cancer initially presenting with paraortic and left supraclavicular lymph node metastases. Methods and Materials: The medical records of 25 patients with both paraortic and left supraclavicular lymph nodal metastases (group I) were reviewed and compared with those of 101 women with paraortic lymph node metastases alone (group II). Group I received a mean 59.4 Gy to the paraortic and left supraclavicular areas and 50.4 Gy to the pelvis, followed by 30 Gy of high-dose-rate brachytherapy in 6 fractions. Group II received the same dose to the paraortic area and pelvis followed by intracavitary brachytherapy. All patients received platinum-based chemotherapy simultaneously. Results: Of the 25 patients in group I, 16 (64%) experienced acute grade 3-4 hematologic toxicities, and 1 had a late grade 3 genitourinary toxicity. Complete responses, including the primary mass and pelvic, paraortic, and left supraclavicular lymph nodes, were observed in 13 patients (52%). At a median follow-up of 32 months for surviving patients, 3 experienced in-field failure, 6 showed distant failure, and 9 showed both. The 3-year overall and disease-free survival rates were 49% and 33%, respectively. In comparison, of the 101 patients in group II, 16 showed in-field failure, 14 experienced distant failure, and 11 showed both. The 3-year overall and disease-free survival rates were 69% and 57%, respectively. Conclusions: Curative CCRT is feasible in patients with stage IVB cervical cancer presenting with paraortic and left supraclavicular lymph nodal metastases, with acceptable late toxicity and high response rates, despite high rates of acute hematologic toxicity. [Copyright &y& Elsevier]