Non-squamous Cell Type Research Articles

Ocena rearanżacji genu ROS1 przy pomocy fluorescencyjnej hybrydyzacji in situ w niedrobnokomórkowym raku płuca

Introduction. The rearrangement of the gene encoding ROS protooncogene (ROS1) is observed in a very small percentage (1–2%) of patients with non-small cell lung cancer (NSCLC). The clinical characteristics of ROS1-positive patients are similar to those observed in the group of patients with ALK gene rearrangement. Detection of ROS1 gene rearrangement is an extremely important predictive factor enabling the use of crizotinib in the 1st line of NSCLC patients with stage IIIB or IV. Due to the addition of crizotinib to the list of reimbursed drugs from January 2019, the analysis of this genetic change should be part of a molecular tests panel performed in patients with locally advanced and advanced NSCLC in the qualification for molecularly targeted treatment. Aim of the study. Analysis of ROS1 gene rearrangement incidence among NSCLC patients in stage IIIB or IV qualified for molecularly targeted therapies. Presentation of methodological difficulties with fluorescent in situ hybridization (FISH) technique which is used to detect ROS1 genetic abnormality. Materials and methods. The analysis of ROS1 gene rearrangement was carried out using fluorescent in situ hybridization technique in tissue samples taken from 573 NSCLC patients of non-squamous cell type during routine pathomorphological diagnostics. Results. The material obtained from the tumor was fixed in formalin and archived in paraffin. Histological material was obtained from 408 patients, and 165 — cytological (cytoblock). A reliable (diagnostic) result of the ROS1 gene rearrangement was obtained in 439 patients (76.61%). The main difficulties for ROS1 gene analysis were low number of cancer cells, as well as high background fluorescence interference and fragmentation of cell nuclei. ROS1 gene rearrangement was detected in 9 patients with adenocarcinoma (1.57% among all patients), including 5 men and 4 women. In 19 patients, other abnormalities regarding the ROS1 gene were observed, primarily the polysomy of the examined ROS1 gene fragment (3.32%). Polysomy did not coexist with the ROS1 rearrangement. Conclusion. Fluorescent in situ hybridization is a useful tool in detecting ROS1 gene rearrangement. The test can be performed in both histological and cytological material (cytoblock). However, the correct fixation of the material and the appropriate number of tumor cells in the tested samples is extremely important for obtaining a reliable result.

Overall Survival in Heart Disease-Related Death in Non-Small Cell Lung Cancer Patients: Nonimmunotherapy Versus Immunotherapy Era: Population-Based Study.

The cardiotoxicity during immunotherapy administration leads to mortality by more than 42% and heart disease–related mortality among immunotherapy-linked cancers is still considered to be underestimated. In this study, the advanced stage of non-small cell lung cancer (NSCLC) with heart disease–related death was selected in accordance with immunotherapy approval time. NSCLC was searched on the Surveillance, Epidemiology, and End Results (SEER) program. Results show that 538 advanced NSCLC cases, those dominated by men and elderly people aged more than 70 years, had a high percentage of heart disease–related death in both eras. The difference between contemporary groups was fairly nonsignificant (P = > 0.05). The overall survival (OS) of all-cause mortality difference showed improved survival in the immunotherapy group (P = 0.0001). In the study of heart disease–related death survival with adjusted data, the NSCLC patients show significant lower survival in the immunotherapy era compared with the nonimmunotherapy era (P = 0.003; hazard ratio [HR] = 1.31; 95% CI = 1.099–1.57). In the multivariate analysis of NSCLC-related immunotherapy, histology revealed that the non-squamous cell type had an independent risk for lower OS than the squamous cell type (P = 0.04; HR= 0.74; CI = 0, 55- 0.99). The results demonstrate the survival benefits for NSCLC in immunotherapy; however, in heart disease–related death, immunotherapy in patients with NSCLC shows decreased OS. This study highlights that NSCLC patients should be highly monitored during immunotherapy administration, and further assessment is needed.

Positive pelvic lymph node on [18F]-FDG PET is a prognostic factor in early-stage high-risk cervical cancer treated by radical hysterectomy and adjuvant chemoradiotherapy

Purpose: The prognostic value of [18F]-fluorodeoxyglucose positron emission tomography (FDG PET) in early-stage high-risk cervical cancer patients was evaluated. Materials and Methods: A total of 86 Stage IB or IIA cervical cancer patients with high risk factors (positive resection margin (RM), parametrial invasion (PI) or pelvic lymph node (PLN) metastasis) were retrospectively investigated. Results: There was a statistically significant decrease in recurrence-free survival (RFS) in patients with bulky tumor (p = 0.011), positive RM (p = 0.001), and PLN positivity on FDG PET (p = 0.012) in multivariate analyses. Independent prognostic factors for overall survival (OS) included non-squamous cell type (p = 0.005), bulky tumor (p = 0.020), and PLN positivity on FDG PET (p = 0.007). Patients with positive PLN on FDG PET had worse five-year RFS (62.0% vs. 85.0%, p = 0.013) and OS (68.7% vs. 89.5%, p = 0.011) rates than those with negative PLN uptake. Conclusion: PLN metastasis on FDG PET and bulky tumor were found to be statistically significant prognostic factors for both RFS and OS in early-stage high-risk cervical cancer patients.

Prognostic model based on magnetic resonance imaging, whole-tumour apparent diffusion coefficient values and HPV genotyping for stage IB-IV cervical cancer patients following chemoradiotherapy.

To develop and validate a prognostic model of integrating whole-tumour apparent diffusion coefficient (ADC) from pretreatment diffusion-weighted (DW) magnetic resonance (MR) imaging with human papillomavirus (HPV) genotyping in predicting the overall survival (OS) and disease-free survival (DFS) for women with stage IB-IV cervical cancer following concurrent chemoradiotherapy (CCRT). We retrospectively analysed three prospectively collected cohorts comprising 300 patients with stage IB-IV cervical cancer treated with CCRT in 2007-2014 and filtered 134 female patients who underwent MR imaging at 3.0 T for final analysis (age, 24-92 years; median, 54 years). Univariate and multivariate Cox regression analyses were used to evaluate the whole-tumour ADC histogram parameters, HPV genotyping and relevant clinical variables in predicting OS and DFS. The dataset was randomly split into training (n = 88) and testing (n = 46) datasets for construction and independent bootstrap validation of the models. The median follow-up time for surviving patients was 69 months (range, 9-126 months). Non-squamous cell type, ADC10 <0.77 × 10-3 mm2/s, T3-4, M1 stage and high-risk HPV status were selected to generate a model, in which the OS and DFS for the low, intermediate and high-risk groups were significantly stratified (p < 0.0001). The prognostic model improved the prediction significantly compared with the International Federation of Gynaecology and Obstetrics (FIGO) stage for both the training and independent testing datasets (p < 0.0001). The prognostic model based on integrated clinical and imaging data could be a useful clinical biomarker to predict OS and DFS in patients with stage IB-IV cervical cancer treated with CCRT. • ADC 10 is the best prognostic factor among ADC parameters in cervical cancer treated with CCRT • A novel prognostic model was built based on histology, ADC 10 , T and M stage and HPV status • The prognostic model outperforms FIGO stage in the survival prediction.

Semi-automatic volumetric measurement of response to chemotherapy in lung cancer patients: How wrong are we using RECIST?

ObjectivesLung cancer typically starts as a near-spherical lesion, but as it grows it may acquire an irregular radiologic formation. RECIST is based on the assumption that tumors are spherical, and consequently, proportional changes of tumor volume and parallel changes in tumor diameter, and vice versa. Hence, a 30% decrease in diameter (2r) implies a 65% decrease of volume, and a 20% increase in diameter implies a 73% increase of volume. Materials and methodsWe compared volumetric measurement based on multi-detector CT technology with calculated volume (CV) according to RECIST in a cohort of 43 patients with advanced, non-squamous cell type, lung cancer treated with a combination of platinum and pemetrexed. ResultsCV was larger than SMV in most patients both at baseline and at best overall response (BOR). The difference between the sum of volumes based on volumetric measurement (SMV) and CV was larger for higher sum of diameters. The Lin's concordance correlation coefficient between the percent changes in SMV and CV at BOR was 0.757. Of note, four patients (4/43, 9.5%) were categorized as PD according to the method of CV, but SD according to the method of SMV. ConclusionOur study highlights the importance of volumetric measurement for assessing response to treatment in lung cancer patients particularly showing large, irregular lesions.

Analysis of non-squamous vulvar cancer cases: A 21-year experience in a single center.

Objective:To evaluate the patients with non-squamous cell type of vulvar cancer who were treated in our clinic within 21 years.Materials and Methods:We assessed the data of 14 patients who were treated for non-squamous cancer of the vulva between January 1992 and August 2013. The age of patients, histopathological diagnosis of the tumor, tumor size, tumor location, medical or surgical treatment, response to the treatment, recurrence, and survival rates were analyzed.Results:The mean age of the patients was 53 years. The main complaint was vulvar pruritus (71%). Mean tumor size was 2.4 cm (range: 0.5-6 cm). In 65% of cases, the tumor was localized in the labia majora. The histopathologic diagnosis of the patients was as follows: malignant melanoma in 5 patients, basal cell carcinoma in 5 patients, mucinous type adenocarcinoma in 2 patients, apocrine gland carcinoma in one patients, and malign peripheral nerve sheath tumor in 1 patient. For 11 patients, surgery was the primary treatment. Radical vulvectomy and bilateral inguinofemoral lymphadenectomy were performed in 8 patients. Local excision alone without lymphadenectomy was performed in other 3 patients. Five of eight patients (62.5%), who undergone radical surgery, had lymph node metastases. Of these 5 patients, two had bilateral lymph node metastasis. Mean follow-up time was 49.2 months (range 12 to 72 months). Eight (57.1%) patients had suffered first recurrence. In those patients, the mean time to recurrence was 19.5 months (range, 6-48 months).Conclusion:Non-squamous cell vulvar cancer is a rare disease and comprises a heterogeneous group of tumors. Malignant melanoma is the most aggressive one. Multicenter prospective studies are necessary in order to standardize the treatment of these rare tumors.

Clinical significance of serum squamous cell carcinoma antigen in the diagnosis, treatment and prognosis of cervical squamous cell carcinoma

To explore the clinical significance of squamous cell carcinoma antigen (SCC-Ag) in the diagnosis, treatment and prognosis of cervical squamous cell carcinoma. The serum SCC-Ag concentrations were measured for 1195 patients with cervical squamous cell carcinoma, 54 patients with non-squamous cell type cervical cancer, 325 patients with cervical intraepithelial neoplasm and 69 healthy women treated at Gynecology Ward of Shengjing Hospital, China Medical University from August 2008 to October 2010. And the correlations with their clinical pathological features of squamous cell carcinoma were analyzed and the changes in the diagnosis, treatment and prognosis monitored. Serum SCC-Ag in patients with cervical squamous cell carcinoma showed a sensitivity of 62.32% and a specificity of 90.10% with the optimal cutoff point of diagnosis at 1.45 µg/L. The differences of pretreatment serum SCC-Ag levels were statistically significant in clinical stage, histological differentiation, depth of invasion and lymph node metastasis (P < 0.01). The posttreatment serum SCC-Ag levels of 106 patients undergoing radical surgery and 264 patients on chemotherapy significantly decreased and were significant different with their pretreatment levels (P < 0.05). There was no relationship of serum SCC-Ag levels and human papillomavirus (HPV) opportunistic infection (all P > 0.05). The best threshold values of pretreatment serum SCC-Ag concentration for predicting early postoperative cervical lymph node metastasis and prognosis of cervical cancer were 2.15 and 12.1 µg/L respectively. As a relatively specific tumor maker for cervical squamous cell carcinoma, squamous cell carcinoma antigen is correlated with clinicopathological features of cervical squamous cell carcinoma. And it has important clinical reference values in the diagnosis, prognosis, follow-up evaluation and treatment monitoring of cervical squamous cell carcinoma.

Clinical Results of Carbon Ion Radiotherapy at NIRS

In 1994 a Phase I/II clinical study on carbon ion radiotherapy was begun at NIRS using HIMAC, which was then the world's only heavy ion accelerator complex dedicated to medical use in a hospital environment. Among several types of ion species, we have chosen carbon ions for cancer therapy because they had the most optimal properties in terms of possessing, both physically and biologically, the most effective dose-localization in the body. The purpose of the clinical study was to investigate the efficacy of carbon ion radiotherapy against a variety of tumors as well as to develop effective techniques for delivering an efficient dose to the tumor. The RBE of carbon ions was estimated to be 2.0 to 3.0 along the SOBP for acute skin reactions. As of August 2006, a total of 2,867 patients had been entered into Phase I/II or Phase II studies and analyzed for toxicity and local tumor response. The results have shown that carbon ion radiotherapy has the potential ability to provide a sufficient dose to the tumor with acceptable morbidity in the surrounding normal tissues. Tumors that appear to respond favorably to carbon ions include locally advanced tumors and those with histologically non-squamous cell type of tumors such as adenocarcinoma, adenoid cystic carcinoma, malignant melanoma, hepatoma, and bone/soft tissue sarcoma. By taking advantage of the biological and physical properties of high-LET radiation, the efficacy of treatment regimens with small fractions in short treatment times has been confirmed for almost all types of tumors in carbon ion radiotherapy.

Overview of clinical experiences on carbon ion radiotherapy at NIRS

Carbon ion beams provide physical and biological advantages over photons. This study summarizes the experiences of carbon ion radiotherapy at the Heavy Ion Medical Accelerator in Chiba (HIMAC) at the National Institute of Radiological Sciences. Between June 1994 and August 2003, a total of 1601 patients with various types of malignant tumors were enrolled in phase I/II dose-escalation studies and clinical phase II studies. All but malignant glioma patients received carbon ion radiotherapy alone with a fraction number and overall treatment time being fixed for each tumor site, given to one field per day and 3 or 4 days per week. In dose-escalation studies, the total dose was escalated by 5 or 10% increments to ensure a safe patient treatment and to determine appropriate dose levels. In the initial dose-escalation studies, severe late complications of the recto-sigmoid colon and esophagus were observed in those patients who received high dose levels for prostate, uterine cervix and esophageal cancer. Such adverse effects, however, did shortly disappear as a result of determining safe dose levels and because of improvements in the irradiation method. Carbon ion radiotherapy has shown improvement of outcome for tumor entities: (a) locally advanced head and neck tumors, in particular those with non-squamous cell histology including adenocarcinoma, adenoid cystic carcinoma, and malignant melanoma; (b) early stage NSCLC and locally advanced NSCLC; (c) locally advanced bone and soft tissue sarcomas not suited for surgical resection; (d) locally advanced hepatocellular carcinomas; (e) locally advanced prostate carcinomas, in particular for high-risk patients; (f) chordoma and chondrosarcoma of the skull base and cervical spine, and (g) post-operative pelvic recurrence of rectal cancer. Treatment of malignant gliomas, pancreatic, uterine cervix, and esophageal cancer is being investigated within dose-escalation studies. There is a rationale for the use of short-course RT regimen due to the superior dose localization and the unique biological properties of high-LET beams. This has been proven in treatment of NSCLC and hepatoma, where the fraction number has been successfully reduced to 4-12 fractions delivered within 1-3 weeks. Even for other types of tumors including prostate cancer, bone/soft tissue sarcoma and head/neck tumors, it was equally possible to apply the therapy in much shorter treatment times as compared to conventional RT regimen. Carbon ion radiotherapy, due to its physical and biologic advantages over photons, has provided improved outcome in terms of minimized toxicity and high local control rates for locally advanced tumors and pathologically non-squamous cell type of tumors. Using carbon ion radiotherapy, hypofractionated radiotherapy with application of larger doses per fraction and a reduction of overall treatment times as compared to conventional radiotherapy was enabled.

Pneumonectomy for stage i (T1N0 and T2N0) nonsmall cell lung cancer has potent, adverse impact on survival

Background Surgically treated, stage I (T1N0 and T2N0) nonsmall cell lung cancer has a relatively favorable prognosis. Our aim was to determine whether performing a pneumonectomy in this group of patients has an impact on survival. Methods Four hundred eighty-five patients with stage I nonsmall cell lung cancer undergoing lung resection between 1991 and 2000 were studied. Three hundred seventy-four patients underwent a smaller resection than a pneumonectomy and 111 had a pneumonectomy. Results Patients undergoing less extensive resections were older (mean age, 65 vs 63 years) ( p = 0.01); these patients were also more likely to have a history of chronic obstructive airway disease (9% vs 2%) ( p = 0.01) or asthma (10% vs 3%) ( p = 0.04), nonsquamous cell type (56% vs 27%) ( p < 0.0001), and T1 tumor stage (66% vs 17%) ( p = 0.002) than patients having a pneumonectomy. Operative mortality was 2.4% versus 8% ( p = 0.01). Overall 1-, 3-, and 5-year Kaplan-Meier survival rates (95% confidence interval [CI]) after less extensive resections were 85% (CI, 82% to 90%), 63% (CI, 56% to 69%), and 50% (CI, 42% to 57%), respectively, and after pneumonectomy the survival rates were 66% (CI, 53% to 73%), 47% (CI, 35% to 57%), and 44% (CI, 32% to 55%), respectively ( p = 0.0006). When the Cox proportional hazards model was applied to all study patients (n = 485), pneumonectomy ( p = 0.001), T2 stage ( p = 0.006), older age ( p = 0.03), and male gender ( p = 0.03) were independent adverse predictors of survival. When the analysis was limited to the patients having T1N0 disease (n = 145), pneumonectomy ( p = 0.0008), older age ( p = 0.05), and nonsquamous cell type ( p = 0.02) were independent adverse determinants of survival. When only the patients with T2N0 disease were analyzed (n = 340), male gender ( p = 0.0005) and pneumonectomy ( p = 0.01) were independent negative predictors of survival. Conclusions In this study, the patients who underwent pneumonectomy for stage T1N0 or T2N0 nonsmall cell lung cancer had a significantly poorer survival than those patients who underwent smaller lung resections.