[Show abstract][Hide abstract] ABSTRACT: Purpose:
This multicenter phase III study evaluated the efficacy and safety of lapatinib, an epidermal growth factor receptor/ErbB2 inhibitor, administered concomitantly with chemoradiotherapy and as maintenance monotherapy in patients with high-risk surgically treated squamous cell carcinoma of the head and neck (SCCHN).
Patients and methods:
Patients with resected stage II to IVA SCCHN, with a surgical margin ≤ 5 mm and/or extracapsular extension, were randomly assigned to chemoradiotherapy (66 Gy total radiation dose and cisplatin 100 mg/m(2) per day administered on days 1, 22, and 43) plus placebo or lapatinib (1,500 mg per day) before and during chemoradiotherapy, followed by 12 months of maintenance monotherapy.
Six hundred eighty-eight patients were enrolled (lapatinib, n = 346; placebo, n = 342). With a median follow-up time of 35.3 months, the study ended early because of the apparent plateauing of disease-free survival (DFS) events. Median DFS assessed by an independent review committee was 53.6 months and not reached for lapatinib and placebo, respectively (hazard ratio, 1.10; 95% CI, 0.85 to 1.43). Investigator-assessed results confirmed the independent review committee assessment. No significant differences in DFS by human papillomavirus status or overall survival were observed between treatment arms. Similar numbers of patients in both treatment arms experienced adverse events (AEs), with more patients in the lapatinib arm than the placebo arm experiencing serious AEs (48% v 40%, respectively). The most commonly observed treatment-related AEs were diarrhea and rash, both predominantly in the lapatinib arm.
Addition of lapatinib to chemoradiotherapy and its use as long-term maintenance therapy does not offer any efficacy benefits and had additional toxicity compared with placebo in patients with surgically treated high-risk SCCHN.
Journal of Clinical Oncology 11/2015; DOI:10.1200/JCO.2015.61.4370 · 18.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients with cytogenetically normal acute myeloid leukemia (CN-AML) can be subdivided by molecular mutations. However, data on the influence of combinations of different aberrations on outcome after allogeneic hematopoietic stem cell transplantation (HSCT) is limited. Therefore, we performed a retrospective registry analysis on 702 adults with CN-AML undergoing HSCT in first complete remission (CR). Patients were grouped according to presence or absence of NPM1 mutations (NPM1(mut)) and FLT3 internal tandem duplications (FLT3-ITD). Double negative patients were evaluated for mutations of the CCAAT/enhancer binding protein α gene (CEBPα). The influence of genotypes on relapse, non-relapse mortality, leukemia-free survival (LFS) and overall survival (OS), and a prognostic classification combining NPM1/FLT3-ITD profile and classical risk factors were calculated. 2y-OS from HSCT was 81±5% in NPM1(mut)/FLT3(wt) (n=68), 75±3% in NPM1(wt)/FLT3(wt) (n=290), 66±3% in NPM1(mut)/FLT3-ITD (n=269) and 54±7% in NPM1(wt)/FLT3-ITD (n=75; p=0.003). Analysis of CEBPα among patients with NPM1(wt)/FLT3(wt) revealed excellent results both in patients with CEBPα(mut) (n=13, 2y-OS:100%), and with a triple negative genotype (n=138, 2y-OS:77±3%). In a Cox-model of predefined factors, older age, presence of FLT3-ITD and >1 course of chemotherapy to reach CR were associated with inferior outcome. 2y-OS/LFS were 88±3%/79±4% in patients without any, 77±2%/73±3% with one, and 53±4%/50±4 with>=2 risk factors (p=0.002 for LFS, p=0.003 for OS). Hence, FLT3-ITD proofed to be the decisive molecular marker for outcome after HSCT for CN-AML in CR1, regardless of NPM1 mutational status, variations of transplant protocols, or development of GvHD. Age, FLT3-ITD and response to induction chemotherapy allow for a prognostic risk classification.
[Show abstract][Hide abstract] ABSTRACT: Background and purpose
The dose effect-effect relationship for cardiac diseases following radiotherapy suffers from uncertainties. Three dimensional coronary artery (CA) dose calculation after mediastinal Hodgkin lymphoma radiotherapy was performed, using the patient’s coronary CT angiography (CCTA), and the relationship between the coronary arteries’ radiation doses and the risk of stenosis was estimated.
Materials and methods
Radiotherapy simulation CT scans and CCTAs of patients treated for a mediastinal Hodgkin lymphoma were used to merge thoracic and detailed cardiovascular anatomies. Radiation treatment parameters were used to estimate CA radiation doses. Twenty-one patients without coronary stenosis (controls) were matched with twelve patients with stenosis (cases). CA segments were considered as sub-volumes of interest. Radiation doses to stenotic segments were compared with those received by normal segments (from cases and controls) using a logistic regression.
In eleven cases out of twelve, the highest of the coronary dose distribution was on a damaged segment. Logistic regression with CA segments yielded an odds ratio associated with the risk of coronary stenosis of 1.049 per additional gray with the CA segment median dose (95% confidence interval, 1.004–1.095; p-value <0.05).
The CA segment dose significantly increased the risk of stenosis on the segment. Such personalized CA dose calculations on larger cohorts are expected to improve the understanding of the cardiovascular radiation dose–effect relationship.
Radiotherapy and Oncology 08/2015; DOI:10.1016/j.radonc.2015.07.043 · 4.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To evaluate the prognostic impact of response to induction chemotherapy preceding salvage HDCT courses, and prior paclitaxel therapy for advanced GCT. This knowledge can help refining the prognosis of patients receiving HDCT.
Twenty-four European centers contributed data. Eligibility included adult male patients with GCT, and treatment with salvage HDCT between the years 2002 and 2012.
Both paclitaxel used in prior lines of therapy and in induction-mobilization regimens pre-HDCT were considered. Multivariable Cox analyses of prespecified factors were undertaken on progression-free (PFS) and overall survival (OS). Missing data were handled by multiple imputation.
Since 10/2013, 324 of 442 registered pts were suitable for present analysis. One hundred ninety-two patients (59.3%) have received paclitaxel-containing regimens. Sixty-one patients (19%) had a progression to induction chemotherapy, 234 (72%) a response (29 [9%] missing or GCSF only). Median follow up was 36 months (IQR: 19-70).
Progression to induction chemotherapy and prior paclitaxel were significantly associated with shorter OS in the univariable model (p<0.001 and p=0.032). However, on multivariable analysis from the model with fully available data (N=216) while progression to induction chemotherapy was significantly prognostic for PFS and OS (HR: 1.92, 95%CI, 1.24-2.98, and HR: 2.09, 95%CI, 1.27-3.42), prior paclitaxel therapy was not: HR: 1.10 (95%CI, 0.70-1.73, p=0.674) and HR: 1.09 (95%CI, 0.64-1.86, p=0.739), respectively. Results were confirmed by the model with imputed data. No significant interaction was found between prior paclitaxel therapy and taxane-containing HDCT (p=0.221 and p=0.077 for PFS and OS).
While progression to induction chemotherapy was independently prognostic, prior paclitaxel was not. Stratification of trials for the latter factor did not appear to be required when accounting for the other clinical predictors.
Keywords: Testicular neoplasms; Germ cell cancer; High-dose chemotherapy; Paclitaxel; Prognostic factors.
[Show abstract][Hide abstract] ABSTRACT: A previous individual patient data meta-analysis by the Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma (MAC-NPC) collaborative group to assess the addition of chemotherapy to radiotherapy showed that it improves overall survival in nasopharyngeal carcinoma. This benefit was restricted to patients receiving concomitant chemotherapy and radiotherapy. The aim of this study was to update the meta-analysis, include recent trials, and to analyse separately the benefit of concomitant plus adjuvant chemotherapy.
The Lancet Oncology 05/2015; 16(6). DOI:10.1016/S1470-2045(15)70126-9 · 24.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The standard treatment of anal canal cancer (ACC) is combined chemotherapy and radiation therapy (RT), which is complex because of the shape of the target volumes and the need to minimize the irradiation of normal pelvic structures. In this study we compared the dosimetric results of helical tomotherapy (HT) plans with traditional 3D conformal RT (3DRT) plans for the treatment of ACC.
Twelve patients (median age 57 years, range 38-83; F/M 8/4) treated with HT and concurrent chemotherapy for locally advanced ACC were selected. All had histologically confirmed squamous-cell carcinoma. A clinical target volume including the tumor and pelvic and inguinal lymph nodes was treated with HT to a total dose of 36 Gy in 1.8-Gy daily fractions. Then a sequential boost of 23.4 Gy in 1.8-Gy daily fractions (total dose 59.4 Gy) was delivered to the tumor and involved nodes. For all 12 patients, 3DRT plans were generated for comparison. Treatment plans were evaluated by means of standard dose-volume histograms. Dose coverage of the planning target volumes (PTVs), homogeneity index (HI), and mean doses to organs at risk (OARs) were compared.
The coverage of PTV was comparable between the two treatment plans. HI was better in the HT vs. 3DRT plans (1.25 and 3.57, respectively; p<0.0001). HT plans resulted in better sparing of OARs (p<0.0001).
HT showed superior target dose conformality and significant sparing of pelvic structures compared with 3DRT. Further investigation should determine if these dosimetric improvements will improve clinical outcomes regarding locoregional control, survival, and treatment-related acute and late morbidity.