Evaluating complete response prediction rates in locally advanced rectal cancer with different radiomics segmentation approaches.

Purpose: Studies examining prediction of complete response (CR) in locally advanced rectum cancer (LARC) from pre/post chemoradiotherapy (CRT) magnetic resonance imaging (MRI) are performed mostly with segmentations of the tumor, whereas only in two studies segmentation included tumor and mesorectum. Additionally, pelvic extramesorectal region, which is included in the clinical target volume (CTV) of radiotherapy, may contain information. Therefore, we aimed to compare predictive rates of radiomics analysis with features extracted from segmentations of tumor, tumor+mesorectum, and CTV. Methods and materials: Ninety-three LARC patients who underwent CRT in our institution between 2012 and 2019 were retrospectively scanned. Patients were divided into CR and non-CR groups. Tumor, tumor+mesorectum and CTV were segmented on T2 preCRT MRI images. Extracted features were compared for best area under the curve (AUC) of CR prediction with 15 machine-learning models. Results: CR was observed in 25 patients (26.8%), of whom 13 had pathological, and 12 had clinical complete response. For tumor, tumor+mesorectum and CTV segmentations, the best AUC were 0.84, 0.81, 0.77 in the training set and 0.85, 0.83 and 0.72 in the test set, respectively; sensitivity and specificity for the test set were 76%, 90%, 76% and 71%, 67% and 62%, respectively. Conclusion: Although the highest AUC result is obtained from the tumor segmentation, the highest accuracy and sensitivity are detected with tumor+mesorectum segmentation and these findings align with previous studies, suggesting that the mesorectum contains valuable insights for CR. The lowest result is obtained with CTV segmentation. More studies with mesorectum and pelvic nodal regions included in segmentation are needed.

Complete Response Evaluation of Locally Advanced Rectal Cancer to Neoadjuvant Chemoradiotherapy Using Textural Features Obtained from T2 Weighted Imaging and ADC Maps.

BACKGROUND: The prediction of pathological responses for locally advanced rectal cancer using magnetic resonance imaging (MRI) after neoadjuvant chemoradiotherapy (CRT) is a challenging task for radiologists, as residual tumor cells can be mistaken for fibrosis. Texture analysis of MR images has been proposed to understand the underlying pathology. OBJECTIVE: This study aimed to assess the responses of lesions to CRT in patients with locally advanced rectal cancer using the first-order textural features of MRI T2-weighted imaging (T2-WI) and apparent diffusion coefficient (ADC) maps. METHODS: Forty-four patients with locally advanced rectal cancer (median age: 57 years) who underwent MRI before and after CRT were enrolled in this retrospective study. The first-order textural parameters of tumors on T2-WI and ADC maps were extracted. The textural features of lesions in pathologic complete responders were compared to partial responders using Student's t- or Mann-Whitney U tests. A comparison of textural features before and after CRT for each group was performed using the Wilcoxon rank sum test. Receiver operating characteristic curves were calculated to detect the diagnostic performance of the ADC. RESULTS: Of the 44 patients evaluated, 22 (50%) were placed in a partial response group and 50% were placed in a complete response group. The ADC changes of the complete responders were statistically more significant than those of the partial responders (P = 0.002). Pathologic total response was predicted with an ADC cut-off of 1310 x 10-6 mm2/s, with a sensitivity of 72%, a specificity of 77%, and an accuracy of 78.1% after neoadjuvant CRT. The skewness of the T2-WI before and after neoadjuvant CRT showed a significant difference in the complete response group compared to the partial response group (P = 0.001 for complete responders vs. P = 0.482 for partial responders). Also, relative T2-WI signal intensity in the complete response group was statistically lower than that of the partial response group after neoadjuvant CRT (P = 0.006). CONCLUSION: As a result of the conversion of tumor cells to fibrosis, the skewness of the T2-WI before and after neoadjuvant CRT was statistically different in the complete response group compared to the partial response group, and the complete response group showed statistically lower relative T2-WI signal intensity than the partial response group after neoadjuvant CRT. Additionally, the ADC cut-off value of 1310 × 10-6 mm2/s could be used as a marker for a complete response along with absolute ADC value changes within this dataset.

Outcomes of thymoma after multimodal therapy and determinants of survival: A 16-year experience of a tertiary cancer center.

BACKGROUND: In this study, we aimed to evaluate the factors that contribute to survival outcomes in patients with thymoma treated with multimodal approaches. METHODS: A total of 203 patients (105 males, 98 females; median age: 49 years; range, 17 to 77 years) with Masaoka-Koga Stage II-IV thymoma between January 2002 and December 2018 were retrospectively analyzed. Data including diagnosis of myasthenia gravis, diagnosis of diabetes mellitus, disease stage, histological type of tumor, capsule invasion and surgical margin status, lymphadenectomy, adjuvant radiotherapy or chemotherapy, time from surgery to the first day of adjuvant treatment, length of hospital stay, and overall and disease-free survival rates were recorded. RESULTS: Of the patients, 91 had Stage II, 67 had Stage III, and 45 had Stage IV disease. A total of 123 patients (61%) had myasthenia gravis. Seventy-six patients received adjuvant radiotherapy and 48 patients received either neoadjuvant (n=35) or adjuvant (n=25) chemotherapy. Higher disease stage, presence of R1 resection, and treatment with chemotherapy were significant factors for decreased disease-free survival time. Older age, higher disease stage, longer postoperative hospital stay, chemotherapy, and disease recurrence were effective contributors to decreased overall survival time. Adjuvant radiotherapy had a statistically significant positive effect on overall survival only in patients with completely resected Stage IV disease (five-year overall survival: 94.7% vs. 79.1%, respectively; p=0.015). In the multivariate analysis, older age (hazard ratio: 4.26), higher disease stage (hazard ratio: 2.95), and longer hospitalization time (hazard ratio: 3.81) were significant prognostic factors for overall survival. Patients with local recurrence who underwent complete resection had a survival time comparable to non-recurrent patients (p=0.753). CONCLUSION: For patients with thymoma, higher disease stage, age ≥50 years, longer hospitalization, and need for chemotherapy are associated with worse survival rates. Adjuvant chemotherapy has a positive impact on Stage IV disease. Resection of recurrent lesions has a valuable impact on survival.

A column generation heuristic for VMAT planning with adaptive CVaR constraints.

In this study we develop an efficient computational procedure that generates medically acceptable treatment plans for volumetric modulated arc therapy with constant gantry speed. Our proposed method is a column generation heuristic based on a mixed integer linear programming model, where the objective function contains minimization of total monitor unit of the treatment plan and dose-volume requirements are included as conditional value-at-risk constraints. Our heuristic generates a full treatment arc for the restricted master problem and calibrates the right hand side parameters of the conditional value-at-risk constraints in the first phase. In the second phase, this initial solution is improved by performing column generation. This is a fully automated procedure and produces treatment plans in a single call without any human intervention. We evaluate its performance on real prostate cancer data by comparing the quality of the generated plans with those obtained by a widely used commercial treatment planning system. Our analysis shows that the results are promising, and the generated plans satisfy the prescription restrictions and require [Formula: see text] fewer monitor units on average compared to the ones obtained using Eclipse.

Neoadjuvant volumetric modulated arc therapy in rectal cancer and the correlation of pathological response with diffusion-weighted MRI and apoptotic markers.

PURPOSE: In this prospective observational study, we aimed to report the applicability and tolerability of neoadjuvant volumetric modulated arc therapy with simultaneous integrated boost (SIB-VMAT) and concurrent chemotherapy in patients with locally advanced rectal cancer (LARC), and to evaluate the correlation of pathological response with apparent diffusion coefficient (ADC) measurements on diffusion-weighted magnetic resonance imaging (DW-MRI) and apoptotic markers. METHODS: The study enrolled 30 patients with T3 to T4 and/or N+ rectal cancer who preoperatively received SIB-VMAT and concurrent chemotherapy. Before and after the neoadjuvant treatment, apoptotic markers including the nucleosomes and cell-free DNA fragments in the serum samples were examined; DNA integrity was assessed by amplifying the ACTB gene; and the ADC measurements on the DW-MRI were analyzed. RESULTS: No patients had acute or chronic grade III-IV toxicity. Pathologic complete response (pCR) was achieved in 8 patients (27%), while in 10 patients (33%) near-complete pathological response was obtained. Posttreatment ADC was significantly higher in patients with pCR compared with the others (1.28 vs. 1.10, p = 0.017). ROC curve analysis showed that posttreatment ADC values had a sensitivity of 75% and a specificity of 77.3% for distinguishing the patients with pCR from other responders. On the other hand, posttreatment DNA integrity values were revealed lower than the pretreatment values (p = 0.36). Also, the results revealed an insignificant increase in the posttreatment serum level of nucleosomes (p = 0.72). CONCLUSIONS: Neoadjuvant SIB-VMAT with concurrent chemotherapy was proved to be a feasible treatment regimen in LARC with tolerable side effects, and improved local control rate and pCR rate.

Concomitant etoposide and cisplatin provided improved survival compared with docetaxel and cisplatin in patients with locally advanced non-small cell lung cancer treated with chemoradiotherapy.

Presently, there is no consensus regarding which chemotherapy regimen is best to administer with radiotherapy in patients with locally advanced non-small-cell lung cancer (LA-NSCLC). Herein, our aim was to compare the outcome of patients treated with either etoposide-cisplatin (EP) or docetaxel-cisplatin (DP) in this curative setting.Patients treated with either EP or DP and concurrent radiotherapy from 2004 to2012 were identified and their detailed medical records and follow-up information were obtained for analysis in this retrospective study. Survival rates were compared using Cox proportional hazards regression models with adjustments for confounding parameters provided by propensity score methods.A total of 105 patients were treated with concurrent chemoradiotherapy for LA-NSCLC (stage IIB-IIIA-IIIB). The median ages were 54 years (range, 32-70 years) and 55 years (range, 37-73 years) in the EP (n = 50) and DP (n = 55) groups, respectively. The median follow-up time was 27 months (range, 1-132 months) in the EP group and 19 months (range, 1-96 months) in DP group. There was no significant difference in baseline clinicopathologic features including age, sex, performance status, histologic subtype, and clinical TNM stages between groups. In the univariate analysis, the median overall survival of patients treated with EP was higher than that of patients treated with DP (41 vs. 20 months, P = 0.003). Multivariate analysis further revealed a survival advantage with EP compared with DP (hazard ratio [HR], 0.46; 95% confidence interval: 0.25-0.83; P = 0.009). The toxicity profile of the 2treatment groups was similar except that pulmonary toxicity was higher in the DP group (grade 3-4: 0% vs. 6%, P = 0.024).Concurrent chemoradiotherapy with EP may provide more favorable outcomes than DP and with an acceptable safety profile.

Association of clinical and pathological variables with survival in thymoma.

Our aim was to evaluate clinical and pathological features in prognosis of thymoma patients with particular emphasis on patients with myasthenia gravis (MG). From 1995 to 2010, 140 thymoma patients (women/men: 63/77) with a median age of 46 years (11-80 years) were admitted to our institution. According to World Health Organization (WHO), there were 23 (17%) type A, 12 (9%) type AB, 24 (17%) type B1, 42 (31%) type B2 and 36 (26%) type B3. The distribution of Masaoka stages I, II, III and IV was 24 (17%), 71 (51%), 18 (13%) and 27 (19%), respectively. MG coexisted in 61% of patients. After a mean follow-up of 34 months (1-158 months), 102 (73%) patients are alive and well while 14 (10%) are alive with disease. Twenty-three patients (16%) have died, only 9 died of thymoma. In univariate analyses, completeness of resection (P < .001), WHO histology (P = .008), Masaoka stage (P < .001) and MG (P = .002) were significant prognostic factors for progression-free survival (PFS). Young age (P = .008); Masaoka stages 1 and 2 (P = .039); WHO types A, AB and B1 (P = .031); complete resection (P = .024) and presence of MG (P = .05) significantly correlated with overall survival (OS). In multivariate analysis, Masaoka stages 1 and 2 (P = .038) and presence of MG (P = .01) were significantly correlated with a longer PFS; MG (P = .021) and WHO subtype (P = .022) were found to be significant prognostic factors for OS. Adjuvant radiotherapy improved neither OS nor PFS in completely resected stage 2 thymoma. Masaoka staging, WHO and MG are major determinants of prognosis in Turkish thymoma patients. Additionally, radiotherapy did not provide survival advantage to stage 2 patients with complete resection.

Induction chemotherapy with triweekly docetaxel and cisplatin followed by concomitant chemoradiotherapy with or without surgery in stage III non-small-cell lung cancer: a phase II study.

BACKGROUND: The main goal of this study was to evaluate the feasibility and effectivity of triweekly docetaxel/cisplatin followed by weekly docetaxel/cisplatin concomitantly with radiotherapy with or without surgery in locally advanced non-small-cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: Thirty five patients with locally advanced NSCLC were enrolled. Combination chemotherapy with triweekly docetaxel/cisplatin (75 mg/m(2)) was administered as induction regimen. After induction chemotherapy, patients were evaluated for surgery if their disease subsequently downstaged. Six cycles of weekly docetaxel/cisplatin (20 mg/m(2)) concurrently with radiotherapy up to a 60 Gy were administered after induction chemotherapy with or without surgery. Response, toxicity, time-to-progression and overall survival were evaluated. RESULTS: Twelve patients with stage IIIA-N2 and 23 patients with stage IIIB-T4N0-2 were evaluated (median age, 54 years). After 94 cycles of induction chemotherapy, partial response was achieved in 20 patients, 9 patients had stable disease and six had progressive disease. After overall treatment, 6 patients achieved complete response, 19 patients had partial response, 8 patients had progressive disease, and 2 patients had stable disease. Two patients experienced grade 3-4 pulmonary toxicity and 1 patient experienced grade 3 esophageal toxicity. Six patients underwent surgery. Median overall survival for all patients was 15 months and time-to-progression was 13 months with a median follow-up of 22 months. CONCLUSION: Triweekly docetaxel plus cisplatin followed by weekly docetaxel plus cisplatin concomitantly with radiotherapy is effective and feasible and seems to be an alternative option for patients who have locally advanced NSCLC. Surgery may provide additional benefit for patients whose disease adequately downstaged after induction chemotherapy.

Weekly docetaxel and cisplatin with concomitant radiotherapy in addition to surgery and/or consolidation chemotherapy in stage III non-small cell lung cancer.

PURPOSE: The aim of this study was to evaluate efficacy and feasibility of a combination of weekly docetaxel and cisplatin administered concomitantly with radiotherapy followed by surgery in addition to consolidation chemotherapy with docetaxel and cisplatin administered every 3 weeks in stage III non-small cell lung cancer (NSCLC). METHODS: A total of 31 histologically proven, locally advanced (stage IIIA-N2 = 9, stage IIIB-T4N0-2 = 22) NSCLC patients were investigated. After administration of 4-6 cycles of weekly docetaxel (20 mg/m(2)) and weekly cisplatin (20 mg/m(2)) concurrently with radiotherapy, patients underwent operation if their disease was appropriately downstaged. Combination chemotherapy with docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) every 3 weeks was administered as a consolidation regimen. The treatment response, toxicity, time to progression (TTP) and overall survival (OS) were evaluated. RESULTS: After concomitant chemoradiotherapy, complete response and partial response occurred in 16.1 and 67.7% of patients, respectively. Thirteen percentage of patients progressed on treatment, and 3.2% had stable disease. Grade 3-4 hematologic and skin toxicities did not occur, whereas 17.9% of them experienced grade 3-4 oesophageal toxicity. Grade 3 pulmonary toxicity and grade 3-4 emesis developed in 9.7 and 6.4% of patients, respectively. Thirteen responsive patients (41.9%) underwent surgery. The toxicity of consolidation chemotherapy was tolerable. Median OS and TTP were 22 ± 5 (range 13-31) and 12 ± 3 (range 7-17) months, respectively. Median follow-up was 22 (range 2-57) months. CONCLUSIONS: Weekly administration of docetaxel and cisplatin concurrently with radiotherapy followed by consolidation chemotherapy is an effective treatment with acceptable toxicity for patients with locally advanced NSCLC especially in combination with surgery.

Lack of diagnostic potential of Dickkopf-1 in colon and rectum cancers.

The Wnt/b-catenin signalling pathway plays crucial roles in development and its aberrant activation is an initial and crucial event in the majority of colon cancers. The Dickkopf-1 (Dkk-1) gene encodes an extracellular Wnt inhibitor that blocks the formation of signalling receptor complexes at the plasma membrane. Here, we report the serum levels of Dkk1 in colorectal cancer patients without any therapy. The levels were determined by enzyme-linked immunosorbent assay (ELISA) in 135 colon and 160 rectum cancer patients, as well as 90 healthy subjects. Data analyses were performed using SPSS software (SPSS 16, Chicago, IL). There were no significant differences among the groups for Dkk-1 (p=0.363). In conclusion, the present study did not confirm that serum Dkk-1 levels could have any diagnostic potential in colon and rectum cancers.

The diagnostic value of macrophage migration inhibitory factor (MIF) in gastric cancer.

The present study was conducted to investigate the sensitivity, specificity, predictive values and accuracy of serum MIF, CEA, CA 19-9 levels and their various combinations in patients with gastric cancer. Study group consists of pathologically verified, gastric cancer (n = 63) and apparently healthy controls (n = 50). Serum MIF concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Serum values of patients were significantly higher than the controls (p = 0.011). Diagnostic sensitivity and specificity, predictive values and accuracies were calculated for each marker and their various combinations. The best results were achieved with the marker combination of MIF-CEA-CA 19-9 and MIF-CEA combination. In our opinion, the combination of the markers MIF-CEA is a valuable diagnostic tool for gastric cancer.

Induction and concurrent chemotherapy with concomitant boost radiotherapy in non-small cell lung cancer.

This study was designed to evaluate the tolerability and therapeutic activity of paclitaxel and carboplatin combination therapy followed by radical thoracic radiotherapy with a concomitant boost technique with concurrent weekly paclitaxel in good performance status of patients with stage IIIA and IIIB non-small cell lung cancer. Patients with newly diagnosed inoperable non-small cell lung cancer received paclitaxel (100 mg/m(2)) as a 1-h infusion on d 1,8,15,28,35, and 42. Carboplatin (area under the curve of 6) was given as a 30-min infusion on d 1 and 28. Radiotherapy commenced on d 49 and was delivered with accelerated fractionation with concomitant boost at 1.8 Gy/fraction/d, 5 d/week and 1.5 Gy/fraction/d to a boost field as a second daily treatment for the last 10 treatment days to 60 Gy/35 fractions/5 wk. During radiation treatment, paclitaxel (60 mg/m(2)) was given as a 1-h infusion once weekly for 5 wk. Twenty-four patients were enrolled in the study. Hematologic toxicities and alopecia were the major acute toxicities during induction chemotherapy; 8.7% of the patients experienced grade 3-4 neutropenia and alopecia. The main acute toxicity of concurrent chemoradiotherapy was esophagitis; grade 3 esophagitis was documented in 23.5% of the patients. No major late toxicity was seen. Overall response rate to the treatment was 65.2%. The median and 1-yr overall-survival rates were 24.9 mo and 63.8%, respectively. The median and 1-yr progression-free survival rates were 9.0 mo and 27.8%, respectively. The main acute toxicities were hematologic toxicity, esophagitis, and alopecia. The response rate and the survival rates achieved with this treatment regimen are particularly noteworthy, especially considering the advanced stage of the patients treated.

The value of serum Bcl-2 levels in advanced lung cancer patients.

Overexpression of the Bcl-2 protein was associated with a favorable prognostic factor for survival in lung cancer patients, especially nonsmall cell lung carcinoma. The present study was conducted to investigate the value of serum Bcl-2 levels in advanced lung cancer patients. Fifty patients with advanced lung carcinoma pathologically verified and 18 healthy controls were investigated. Serum samples were obtained on the first admission before the chemotherapeutic treatment were given. Serum Bcl-2 levels were determined by using anti-Bcl-2 monoclonal coating antibody. The baseline serum Bcl-2 levels were significantly higher in patients with lung cancer than in the control group (p<0.001). Serum Bcl-2 levels were elevated in 48 (96%) advanced lung cancer patients. None of the prognostic parameters analyzed, such as age of patient, gender, histology, stage of disease, erythrocyte sedimentation rate, serum albumin, hemoglobin, CEA, NSE, LDH, performance of patient, weight loss, and response to chemotherapy, was significantly correlated with Bcl-2 serum concentrations. The serum Bcl-2 concentrations were not changed with cisplatin-based cytotoxic chemotherapy regardless of response (p=0.76). No prognostic value of serum Bcl-2 was determined. In conclusion, the results of the present study, which is the first study to determine serum Bcl-2 levels in lung cancer, suggest that decreased apoptosis occurred due to the effect of serum Bcl-2 elevation in lung cancer patients. Serum Bcl-2 level was of diagnostic but not prognostic value in lung cancer patients. However, more studies are needed to define the role of Bcl-2 in the diagnosis and prognosis of lung cancer.