Concomitant administration of radiation therapy (RT) and chemotherapy with cisplatin (CCRT) is considered standard treatment in patients with locally advanced nasopharyngeal cancer (LA-NPC). The role ...of induction chemotherapy (IC) when followed by CCRT in improving locoregional control remains controversial.
Totally, 141 eligible patients with LA-NPC were randomized to either three cycles of IC with cisplatin 75 mg/m2, epirubicin 75 mg/m2 and paclitaxel (Taxol) 175 mg/m2 (CEP) every 3 weeks followed by definitive RT (70 Gy) and concomitant weekly infusion of cisplatin 40 mg/m2 (investigational arm, 72 patients) or to the same CCRT regimen alone (control arm, 69 patients).
Sixty-two patients (86%) received three cycles of IC. No difference between the arms was observed in the number of patients who completed RT (61 versus 64, P = 018). Overall and complete response rates were very similar in the two arms and so were 3-year progression-free and overall survival rates. Grade III or IV toxic effects from IC were infrequent, apart of alopecia. Mucositis, weight loss and leukopenia were the most prominent side-effects from CCRT.
IC with three cycles of CEP when followed by CCRT did not significantly improve response rates and/or survival compared with that of CCRT alone.
The peculiar dermatoscopic pattern of scalp melanoma Spyridis, I.; Papageorgiou, C.; Apalla, Z. ...
Journal of the European Academy of Dermatology and Venereology,
September 2022, Letnik:
36, Številka:
9
Journal Article
Recenzirano
Background
Melanomas developing on anatomic sites other than the trunk and extremities have a special pathogenetic and mutational profile, morphologic characteristics and biologic behaviour.
...Objective
By retrospectively screening the databases of our centres, we aimed to investigate the dermatoscopic morphology of early scalp melanoma, including in situ and invasive tumours with a Breslow thickness up to 1 mm.
Methods
The databases of three specialized centres for skin cancer diagnosis and management in Greece were retrospectively evaluated to retrieve dermatoscopic images of scalp melanomas. Patients' age and sex were recorded, as well as the precise location of the tumour, using 6 possible sub‐locations: frontal, parietal, occipital, temporal, nuchal scalp and vertex. The dermatoscopic images were evaluated by 3 independent investigators for the presence of pre‐defined criteria. The dermatoscopic criteria included in the evaluation were selected based on available literature and were categorized in 2 groups: ‘classic melanoma criteria’ and ‘lentigo maligna (LM) criteria’.
Results
Of 38 melanomas, 37 (97.4%) displayed brown colour and 23 (60.5%) displayed additional grey or blue colour. The most frequent dermatoscopic criteria were regression (18/38, 47.4%), grey dots/globules (17/38, 44.7%), atypical network (16/38, 42.1%), obliterated follicles (16/38, 42.1%) and angulated lines (15/38, 39.5%). Of 38 melanomas, 28 (73.7%) displayed at least 1 classic melanoma criterion plus at least 1 LM criterion. Of the remaining melanomas, 8 (21.1%) displayed only classic melanoma criteria, 1 (2.6%) only LM criteria and 1 (2.6%) did not exhibit any of the evaluated criteria.
Conclusions
This study demonstrates that early scalp melanoma combines classic with LM criteria in terms of colours and structures.
Trastuzumab (T) is effective in metastatic breast cancer (MBC) with HER2 overexpression and/or amplification, but resistance to T develops in a significant number of HER2-positive patients. ...Understanding the mechanisms of resistance is critical to the care of these patients. Formalin-fixed paraffin-embedded tumor tissue samples were collected from 256 patients with T-treated MBC. Clinical information was collected retrospectively from the patients’ medical records. Central review of HER2 status by fluorescent in situ hybridization (FISH) and/or immunohistochemistry (IHC) revealed that of the 227 eligible patients only 139 (61%) were truly HER2-positive. PTEN, ER, PgR, and Ki67 were evaluated by IHC, while PTEN status was evaluated by FISH as well. PIK3CA mutations were identified with single nucleotide polymorphism (SNP) genotyping. Median time to progression (TTP) was 14.4 months for the HER2-positive and 10.3 for the HER2-negative patients (log-rank,
P
= 0.22). Survival from the initiation of T (survivalT) was 50.4 months for the HER2-positive and 35.3 for the HER2-negative subgroups (
P
= 0.006). Higher risk of progression was associated with HER2-positive status and the presence of PIK3CA mutations (
P
= 0.014). PTEN loss, as determined by IHC, was associated with lower survivalT in the whole population (
P
= 0.029) and in the HER2-positive population (
P
= 0.017). PIK3CA mutations and/or PTEN loss status were evaluated together as a single parameter, to estimate the impact of activation of the PI3K/AKT molecular pathway, and it was significantly associated with both decreased TTP (
P
= 0.003 in the total population,
P
= 0.004 in HER2-positive patients) and survival (survivalT,
P
= 0.011 in total,
P
= 0.006 in HER2-positive). In this trastuzumab-treated breast cancer population, PIK3CA activating mutations were associated with shorter TTP and PTEN loss with decreased survival. The activation of the PI3K/AKT pathway from either defect was associated with both TTP and survival, indicating the adverse effect of this pathway’s status on trastuzumab efficacy.
Purpose
RACGAP1 is a Rac GTPase-activating protein involved in cell growth regulation, cell transformation and metastasis. The aim of the present study was to explore the prognostic and/or predictive ...significance of RACGAP1 mRNA expression on disease-free survival (DFS) and overall survival (OS) in high-risk early breast cancer patients and compare it to that of Ki67 protein expression and to the Nottingham prognostic index (NPI).
Methods
A total of 595 high-risk breast cancer patients were treated in a two-arm trial evaluating postoperative dose-dense sequential chemotherapy with epirubicin followed by CMF with or without paclitaxel. RNA was extracted from 314 formalin-fixed paraffin-embedded primary tumor tissue samples followed by one-step quantitative RT-PCR for assessing RACGAP1 mRNA expression.
Results
High RACGAP1 mRNA expression (above the median) was associated with poor DFS (log-rank,
p
= 0.002) and OS (
p
< 0.001). High histological grade, as well as high Ki67 protein expression, was more frequent in the high-expression group of RACGAP1. Results of the Cox multivariate regression analysis revealed that high RACGAP1 mRNA expression independently predicted poor overall survival (Wald’s
p
= 0.008). High Ki67 protein expression was also an adverse prognostic factor for death (
p
= 0.016), while high NPI score values were not.
Conclusions
High RACGAP1 mRNA expression, as assessed by qRT-PCR, was found to be of adverse prognostic significance in high-risk early breast cancer patients treated with dose-dense sequential chemotherapy. The utility of RACGAP1 mRNA expression in patient selection for treatment with aggressive chemotherapy regimens should be further explored and validated in larger cohorts.
Hypothesising that cancer of unknown primary (CUP) may harbour unique characteristics, we present a translational study of the immunohistochemical expression and clinical correlation of key PTEN/AKT ...pathway molecules.
We collected 100 paraffin-embedded CUP tissue blocks. We studied using tissue microarrays the expression of PTEN, phospho-AKT, Cyclin D1, p21, phospho-RPS6. From the percentage of staining tumour cells and the literature, we selected cut-offs to classify the expression of each biomolecule. We correlated IHC expression with clinical data.
PTEN, pAKT, and pRPS6 showed frequent expression. At univariate analysis, high IHC expression of pAKT and pRPS6 displayed statistically significant association with worse survival. Prognosis was worse upon concurrent high IHC expression of pMAPK and pAKT {median overall survival = 8 months 95% confidence interval (CI) 5.3–10.7 versus 17 months 95% CI 13.1–20.9}. In multivariate analysis, high p21 was associated with better survival (risk ratio RR = 0.34 95% CI 0.16–0.73, P = 0.005). High expression of pAKT (RR = 2.39 95% CI 1.23–4.66, P = 0.01) or pRPS6 (RR = 2.76 95% CI 1.31–5.84, P = 0.008) was associated with worse survival.
p21 expression conferred favourable prognosis, while high pAKT or pRPS6 expression predicted worse prognosis. Concurrent MAPK and pAKT expression had a marked adverse impact on survival.
Despite improvement in therapeutic techniques, patients with early-stage laryngeal cancer still recur after treatment. Gene expression prognostic models could suggest which of these patients would be ...more appropriate for testing adjuvant strategies.
Expression profiling using whole-genome DASL arrays was carried out on 56 formalin-fixed paraffin-embedded tumor samples of patients with early-stage laryngeal cancer. We split the samples into a training and a validation set. Using the supervised principal components survival analysis in the first cohort, we identified gene expression profiles that predict the risk of recurrence. These profiles were then validated in an independent cohort.
Gene models comprising different number of genes identified a subgroup of patients who were at high risk of recurrence. Of these, the best prognostic model distinguished between a high- and a low-risk group (log-rank P < 0.005). The prognostic value of this model was reproduced in the validation cohort (median disease-free survival: 38 versus 161 months, log-rank P = 0.018), hazard ratio = 5.19 (95% confidence interval 1.14–23.57, P < 0.05).
We have identified gene expression prognostic models that can refine the estimation of a patient's risk of recurrence. These findings, if further validated, should aid in patient stratification for testing adjuvant treatment strategies.
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