PURPOSE Differentiating the irinotecan dose on the basis of the uridine diphosphate glucuronosyltransferase 1A1 ( UGT1A1) genotype improves the pathologic complete response (pCR) rate. In this study, we further investigated preoperative irinotecan combined with capecitabine-based chemoradiotherapy for locally advanced rectal cancer. PATIENTS AND METHODS We conducted this randomized, open-label, multicenter, phase III trial in China. Eligible patients with clinical T3-4 and/or N+ rectal adenocarcinoma, UGT1A1 genotype *1*1 or *1*28 were randomly allocated to the control group: pelvic radiation of 50 Gy/25 fractions with concurrent capecitabine, followed by oxaliplatin and capecitabine; or the experimental group: radiation with capecitabine combined with weekly irinotecan 80 mg/m2 for patients with UGT1A1*1*1 or 65 mg/m2 for patients with UGT1A1*1*28, followed by irinotecan and capecitabine. The primary end point was pCR. This trial was registered with ClinicalTrials.gov (ClinicalTrials.gov identifier: NCT02605265). RESULTS Of the 360 patients initially enrolled, 356 were evaluated as the modified intention-to-treat population (n = 178 in both groups). Surgery was performed in 87% and 88% of patients in the control and experimental groups, respectively. The pCR rates were 15% (n = 27 of 178) and 30% (n = 53 of 178) in the control and experimental groups (risk ratio, 1.96; 95% CI, 1.30 to 2.97; P = .001). Four and 6 patients achieved complete clinical response in the control and experimental groups, respectively. Grade 3-4 toxicities were recorded in 11 (6%) and 68 (38%) patients in the control and experimental groups, respectively ( P < .001). The commonest grade 3-4 toxicities were leukopenia, neutropenia, and diarrhea. The overall surgical complication rate was not significantly different between the two groups (11% v 15%; P < .001). CONCLUSION Adding irinotecan guided by UGT1A1 genotype to capecitabine-based neoadjuvant chemoradiotherapy significantly increased complete tumor response in Chinese patients.

BackgroundA phase II study of methotrexate, etoposide, dexamethasone, and pegaspargase (MESA) sandwiched with radiotherapy for newly diagnosed, stage IE-IIE extranodal natural-killer/T-cell lymphoma, nasal-type (ENKTL) was conducted to explore its clinical efficacy and safety, as well as novel serum biomarkers upon anti-metabolic treatment.MethodsFour cycles of MESA sandwiched with radiotherapy were administered. The primary end point was the overall response rate (ORR). Serum metabolomic profiles were assessed by liquid chromatography-mass spectrometry, with specific metabolites quantified by targeted metabolic analysis.FindingsForty patients were enrolled and the ORR was 92.1% (95%CI, 83.1%–100.0%). The 2-year progression-free survival (PFS) rate was 89.1% and overall survival (OS) rate was 92.0%. Grade 3/4 non-hematologic and hematologic toxicities were observed in 17 (42.5%) and 26 patients (65·0%) during chemotherapy, and in 9 (22.5%) and 0 (0.0%) patients during radiotherapy, respectively. Fifty-six significantly decreased and 59 increased metabolites were identified in ENKTL, as compared to healthy volunteers. A predictive principal components analysis model of asparaginase-associated metabolites, asparaginase-associated metabolic score (AspM), was established, including alanine, aspartate, glutamate, and succinic acid. Patients with high AspM score displayed superior survival and prognostic significance of AspM was validated in a historical cohort of early and advanced-stage ENKTL treated with asparaginase-based regimens. Multivariate analysis confirmed AspM as a prognostic score independent of PINK and PINK combined with Epstein-Barr virus DNA.InterpretationMESA sandwiched with radiotherapy is an effective and safe regimen for early-stage ENKTL. AspM score may be a promising prognostic index of serum metabolites in addition to clinical prognostic index in ENKTL.

AimThis study was designed to evaluate the efficacy and toxicities of concomitant boost intensity-modulated radiation therapy (IMRT) along with capecitabine and oxaliplatin, followed by a cycle of Xelox, in neoadjuvant course for locally advanced rectal cancer.Materials and methodsPatients with histologically confirmed, newly diagnosed, locally advanced rectal adenocarcinoma (cT3-T4 and/or cN+) located within 12 cm of the anal verge were included in this study. Patients received IMRT to the pelvis of 50 Gy and a concomitant boost of 5 Gy to the primary tumor in 25 fractions, and concurrent with oxaliplatin (50 mg/m2 d1 weekly) and capecitabine (625 mg/m2 bid d1–5 weekly). One cycle of Xelox (oxaliplatin 130 mg/m2 on d1 and capecitabine 1000 mg/m2 twice daily d1–14) was given two weeks after the completion of chemoradiation, and radical surgery was scheduled eight weeks after chemoradiation. Tumor response was evaluated by tumor regression grade (TRG) system and acute toxicities were evaluated by NCI-CTC 3.0 criteria. Survival curves were estimated using the Kaplan-Meier method and compared with Log-rank test.ResultsA total of 78 patients were included between March 2009 and May 2011 (median age 54 years; 62 male). Seventy-six patients underwent surgical resection. Twenty-eight patients underwent sphincter-sparing lower anterior resection and 18 patients (23.7%) were evaluated as pathological complete response (pCR). The incidences of grade 3 hematologic toxicity, diarrhea, and radiation dermatitis were 3.8%, 10.3%, and 17.9%, respectively. The three-year LR (local recurrence), DFS (disease-free survival) and OS (overall survival) rates were 14.6%, 63.8% and 77.4%, respectively. Initial clinical T stage and tumor regression were independent prognostic factors to DFS.ConclusionAn intensified regimen of concomitant boost radiotherapy plus concurrent capecitabine and oxaliplatin, followed by one cycle of Xelox, can be safely administered in patients with locally advanced rectal cancer, and produces a high rate of pCR. A prognostic score model is helpful to distinguish different long-term prognosis groups in early stage.

Background: Conventional post-mastectomy radiation therapy is delivered with tangential fields for chest wall and separate fields for regional nodes. Although chest wall and regional nodes delineation has been discussed with RTOG contouring atlas, CT-based planning to treat chest wall and regional nodes as a whole target has not been widely accepted. We herein discuss the dosimetric characteristics of a linac IMRT technique for treating chest wall and regional nodes as a whole PTV after modified radical mastectomy, and observe acute toxicities following irradiation. Methods: Patients indicated for PMRT were eligible. Chest wall and supra/infraclavicular region +/−internal mammary nodes were contoured as a whole PTV on planning CT. A simplified linac IMRT plan was designed using either integrated full beams or two segments of half beams split at caudal edge of clavicle head. DVHs were used to evaluate plans. The acute toxicities were followed up regularly.