The prognostic value of haematologic parameter changes during treatment in cervical cancer patients treated with definitive chemoradiotherapy.

We retrospectively analysed the prognostic significance of changes in absolute neutrophil count (ANC), absolute lymphocyte count (ALC) and neutrophil/lymphocyte ratio (NLR) during treatment with definitive chemoradiotherapy (CRT) in 104 cervical cancer patients. The absolute white blood cell, ANC and ALC decrease during treatment, NLR increased throughout treatment and reached to a plateau at fifth week. The ANC and NLR after 3rd week of definitive CRT were significantly higher and ALC after 3rd week of treatment was significantly lower in patients with progressive disease compared patients with no evidence of disease. Patients in low-haematological risk (LHR) group had significantly higher number of patients with smaller tumour size, early stage disease and without lymph node metastasis. In multivariate analysis, high-haematological risk (HHR) group and lymph node metastasis were negative prognosticators of overall and disease-free survival (DFS). The presence of lymph node metastasis and HHR could serve as a predicative factor of poor prognosis for cervical cancer patients. IMPACT STATEMENT What is already known on this subject? The ANC and NLR after 3rd week of definitive CRT were significantly higher and ALC after 3rd week of treatment was significantly lower in patients with progressive disease compared patients with no evidence of disease. Patients in LHR group had significantly higher number of patients with smaller tumour size, early stage disease and without lymph node metastasis. Lymph node metastasis and HHR and were negative prognosticators of overall and disease-free survival (DFS). The presence of lymph node metastasis and HHR could serve as a predicative factor of poor prognosis for cervical cancer patients. What the results of this study add? Weekly changes in ANC, ALC, and NLR, especially after 3rd week of treatment are predictive factors of disease progression, not the high-risk features of disease. Furthermore, in HHR group more patients with extensive stage disease, larger tumour and lymph node metastasis were observed compared to LHR group. What the implications are of these findings for clinical practice and/or further research? The patients may be stratified according to risk factors. The treatment intensification maybe required for HHR patients compared to LHR patients. Since our findings are preliminary, further studies are required to support these findings.

Prognostic value of the Glasgow Prognostic Score for glioblastoma multiforme patients treated with radiotherapy and temozolomide.

INTRODUCTION: To evaluate the prognostic value of the Glasgow Prognostic Score (GPS), the combination of C-reactive protein (CRP) and albumin, in glioblastoma multiforme (GBM) patients treated with radiotherapy (RT) and concurrent plus adjuvant temozolomide (GPS). METHODS: Data of newly diagnosed GBM patients treated with partial brain RT and concurrent and adjuvant TMZ were retrospectively analyzed. The patients were grouped into three according to the GPS criteria: GPS-0: CRP < 10 mg/L and albumin > 35 g/L; GPS-1: CRP < 10 mg/L and albumin < 35 g/L or CRP > 10 mg/L and albumin > 35 g/L; and GPS-2: CRP > 10 mg/L and albumin < 35 g/L. Primary end-point was the association between the GPS groups and the overall survival (OS) outcomes. RESULTS: A total of 142 patients were analyzed (median age: 58 years, 66.2% male). There were 64 (45.1%), 40 (28.2%), and 38 (26.7%) patients in GPS-0, GPS-1, and GPS-2 groups, respectively. At median 15.7 months follow-up, the respective median and 5-year OS rates for the whole cohort were 16.2 months (95% CI 12.7-19.7) and 9.5%. In multivariate analyses GPS grouping emerged independently associated with the median OS (P < 0.001) in addition to the extent of surgery (P = 0.032), Karnofsky performance status (P = 0.009), and the Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) classification (P < 0.001). The GPS grouping and the RTOG RPA classification were found to be strongly correlated in prognostic stratification of GBM patients (correlation coefficient: 0.42; P < 0.001). CONCLUSIONS: The GPS appeared to be useful in prognostic stratification of GBM patients into three groups with significantly different survival durations resembling the RTOG RPA classification.

Prognostic Use of Pretreatment Hematologic Parameters in Patients Receiving Definitive Chemoradiotherapy for Cervical Cancer.

OBJECTIVES: The aim of this work was to evaluate the prognostic role of pretreatment neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in recipients of definitive chemoradiotherapy (ChRT) for cervical cancer. METHODS: In 235 patients given definitive ChRT for histologically confirmed cervical cancer, clinical data and pretreatment complete blood cell counts were analyzed. Prognostic and therapeutic ramifications of NLR and PLR were assessed. RESULTS: Median pretreatment NLR and PLR were 3.03 (range, 1.04-13.03) and 133.02 (range, 36.3-518.16), respectively. Both NLR and PLR correlated significantly with tumor size, lymph node metastasis, and treatment response. In addition to NLR and PLR, tumor stage, size, and nodal metastasis were identified by univariate analysis as significant predictors of overall survival (OS) and progression-free survival (PFS). By multivariate analysis, independent predictors of OS and PFS were NLR (OS: hazard ratio [HR], 3.322; 95% confidence interval [CI], 1.905-5.790; PFS: HR, 3.579; 95% CI, 2.106-6.082; both P < 0.001) and lymph node metastasis (OS: HR, 2.620; 95% CI, 1.706-4.023; PFS: HR, 2.989; 95% CI, 1.918-4.378; both P < 0.001), although patients' age (HR, 1.019; 95% CI, 1.003-1.035; P = 0.02) was also significantly predictive of OS. CONCLUSIONS: Pretreatment NLR and PLR were associated with larger tumors, lymph node metastasis, and poorer therapeutic responses to definitive ChRT. By multivariate analysis, pretreatment NLR and lymph node metastasis were found independently predictive of OS and PFS, whereas patients' age was significantly predictive of OS only. In patients with advanced cervical cancer, NLR is a potential biomarker, serving to guide systemic therapy and predict treatment outcomes.

Dosimetric Comparison of Sequential Versus Simultaneous-integrated Boost in Early-stage Breast Cancer Patients Treated With Breast-conserving Surgery.

BACKGROUND/AIM: To compare simultaneous-integrated boost (SIB) versus sequential-boost (SB) delivered in the context of whole-breast irradiation (WBI) via volumetric-modulated arc therapy (VMAT) and helical-tomotherapy (HT). MATERIALS AND METHODS: Planning target-volume (PTV) dosimetric parameters and organs at risk (OAR) were analyzed for SB plan (50 Gy plus 16 Gy boost) and SIB plan (50.4 Gy WBI and 64.4 Gy tumor bed boost) in VMAT and HT techniques. RESULTS: Conformity and homogeneity for target-volume doses were better in HT plans compared to VMAT plans. There were no significant differences in ipsilateral lung doses between VMAT and HT plans for SB/SIB techniques, except for a significantly higher lung V5 value with VMAT-SB, and lung V13 value with HT-SIB technique. HT provided a statistically significant decrease in contralateral lung mean V5. CONCLUSION: The SIB technique showed better target-volume dose distribution in both HT and VMAT plans, and better sparing heart in HT compared to the SB technique.

Prognostic value of metabolic tumor volume and total lesion glycolysis in esophageal carcinoma patients treated with definitive chemoradiotherapy.

PURPOSE: The aim of this study was to evaluate the prognostic importance metabolic tumor volume (MTV), total lesion glycolysis (TLG), and standardized uptake value (SUV) in patients with esophageal cancer treated with definitive chemoradiotherapy. PATIENTS AND METHODS: Seventy-two esophageal cancer patients treated with definitive chemoradiotherapy [57 (79%) patients] or definitive radiotherapy [15 (21%) patients] were retrospectively analyzed. The regions equal to or greater than SUV of 2.5 were selected to delineate MTV and TLG was calculated by multiplying the mean SUV by the MTV of the primary lesions. The overall survival (OS) and disease-free survival (DFS) were evaluated for all patients and also patients with squamous cell carcinoma. RESULTS: The median survival time was 13.4 months (range: 1.8-119.3 months) for all patients. Maximum SUV, mean SUV, MTV, and TLG values were significantly higher in patients with extensive T-stage (T3-T4) compared with patients with T1-T2 disease. Patients with regional lymph node metastasis had significantly higher MTV and TLG values compared with patients with no lymph node metastasis. On multivariate analysis, MTV, TLG, presence of lymph node metastasis, and lack of concurrent chemotherapy were negative significant prognostic factors for OS and DFS for the entire cohort and for patients with squamous cell carcinoma esophageal cancer. CONCLUSION: Metabolic volumes (MTV and TLG), regional lymph node metastasis, and concurrent chemotherapy are major prognostic factors for DFS and OS in patients with esophageal carcinoma. In addition, MTV and TLG are important in predicting nodal metastasis, and together with metabolic volumes, SUV are associated significantly with local tumor invasion.

Chemoradiotherapy-induced hemoglobin nadir values and survival in patients with stage III non-small cell lung cancer.

PURPOSE: We investigated the influence of change in hemoglobin (Hgb) levels during concurrent chemoradiotherapy (C-CRT) on outcomes of non-anemic patients with stage IIIA/B non-small cell lung cancer (NSCLC). METHODS: We identified 722 patients with stage IIIA/B NSCLC without anemia at baseline [hemoglobin (Hgb) <12 g/dL for women or <13 g/dL for men], either nonsmokers or ex-smokers, who received C-CRT between 2007 and 2012. All patients had received 1-3 cycles of platinum-based doublet chemotherapy during radiotherapy to 60-66 Gy and had documented Hgb measurements before treatment and at weekly intervals for 6 weeks during the C-CRT. Potential associations were assessed between baseline, nadir, extent of change in Hgb level, and anemia and overall survival (OS), locoregional progression-free survival (LRPFS), and PFS. RESULTS: The median baseline Hgb level was 13.9 g/dL (range 12.0-16.8) and declined to a median 12.4 g/dL (range 7.9-16.1) during treatment. Anemia appeared in 237 patients (32.8%) and was more common among women (44.8% vs. 26.5%, P < 0.001). Neither baseline Hgb level nor change during treatment nor anemia emergence influenced any survival endpoint. Receiver operating curve analysis revealed an Hgb nadir of 11.1 g/dL to be associated with outcomes, in that a nadir Hgb <11.1 g/dL (in 156 patients) was linked with shorter median OS time (P < 0.001), LRPFS time (P < 0.001), and PFS time (P < 0.001); retained significance for all three endpoints in multivariate analyses; and was more strongly associated with OS in squamous cell carcinoma (P < 0.001) than in adenocarcinoma (P = 0.009). CONCLUSION: Nadir Hgb <11.1 g/dL levels during C-CRT were associated with significantly poorer survival times in initially non-anemic patients presenting with locally advanced NSCLC.

Risk Factors for Fatal Pulmonary Hemorrhage following Concurrent Chemoradiotherapy in Stage 3B/C Squamous-Cell Lung Carcinoma Patients.

We aimed to identify the fatal pulmonary hemorrhage- (FPH-) related risk factors in stage 3B/C squamous-cell lung carcinoma (SqCLC) patients treated with definitive concurrent chemoradiotherapy (C-CRT). Medical records of 505 stage 3B/C SqCLC patients who underwent 66 Gy radiotherapy plus 1-3 cycles of concurrent chemotherapy with available pretreatment thoracic computerized tomography scans were retrospectively analyzed. Primary end-point was the identification of FPH-related risk factors. Examined factors included the basal patient and tumor characteristics with specific emphasis on the tumor cavitation (TC) status, tumor size (TS) and cavitation size (CS), tumor volume and cavitation volume (TV and CV), relative cavitation size (RCS = CS/TS), and relative cavitation volume (RCV=CV/TV). FPH emerged in 13 (2.6%) patients, with 12 (92.3%) of them being diagnosed ≤12 months of C-CRT. All FPHs were diagnosed in patients with TC (N=60): group-specific FPH incidence: 21.6%. TC (P<0.001) was the unique independent factor associated with higher FPH risk in multivariate analysis. Further analysis limited to TC patients exhibited the RCV>0.14 (37.5% versus 11.1% for RCV≤0.14; P<0.001), major RCS group [31.0% versus 19.0% for minor versus 0% for minimum RCS; P=0.008), and baseline hemoptysis (26.3% versus 13.6% for no hemoptysis; P=0.009) as the independent risk factors for higher FPH incidence. FPH was an infrequent (2.6%) complication of C-CRT in stage 3B/C SqCLC patients, but its incidence increased to 37.5% in patients presenting with TC and RCV>0.14. Diagnosis of >90% FPHs ≤12 months of C-CRT stresses the importance of close and careful follow-up of high-risk patients after C-CRT for multidisciplinary discussion of possible invasive preventive measures.

Incidence and Impact of Pretreatment Tumor Cavitation on Survival Outcomes of Stage III Squamous Cell Lung Cancer Patients Treated With Radical Concurrent Chemoradiation Therapy.

PURPOSE: To investigate the incidence and influence of tumor cavitation (TC) on survival outcomes of locally advanced squamous cell lung cancer (LA-SqCLC) patients treated with concurrent chemoradiation therapy (C-CRT). METHODS AND MATERIALS: Records of 789 stages IIIA/B squamous cell lung cancer (SqCLC) patients treated with C-CRT who received 1 to 3 cycles of platinum-based doublet chemotherapy during 60 to 66 Gy radiation therapy (RT) were analyzed retrospectively. Primary endpoint was the association between overall survival (OS) and pretreatment TC status. Secondary endpoints included locoregional progression-free survival (LRPFS), progression-free survival (PFS), and incidence of TC and correlated factors. RESULTS: Pretreatment TC occurred in 95 patients (12%), being significantly more common in those patients with ever-smoking history (12.6% vs 3.9%; P < .001), weight loss >5% (20.9% vs 7.1%; P < .001), and hemoptysis (27.1% vs 6.4%; P < .001). Rates of acute and late toxicities were similar in patients who presented with and without TC (P > .05 for each). For the whole cohort, at a median follow-up of 22.9 months (range: 2.4-71.1), the respective median OS, LRPFS, and PFS estimates were 23.7, 14.7, and 10.7 months. In multivariate analysis, stage IIIB disease (P < .001; hazard ratio [HR]: 1.33; 95% CI: 1.21-1.45), weight loss >5% (P < .001; HR: 2.10; 95% CI: 1.85-2.35), anemia (P < .001; HR: 1.82; 95% CI: 1.67-1.97), and presence of TC (P < .001; HR: 1.54; 95% CI: 1.37-1.71) appeared to be independently associated with poorer OS durations, likewise the LRPFS (P < .001 for each of these covariates), and PFS (P < .001 for each of these covariates), respectively. CONCLUSIONS: Present results showed that the TC occurred in 12% of LA-SqCLC patients, which was strongly associated with poorer PFS, LRPFS, and OS outcomes after definitive C-CRT.

Is it essential to use fiducial markers during cone-beam CT-based radiotherapy for prostate cancer patients?

PURPOSE: To compare soft-tissue cone-beam computed tomography (CBCT-P) and fiducial marker (CBCT-FM)-based image guided radiotherapy in prostate cancer patients. MATERIALS AND METHODS: Sixteen prostate cancer patients were treated with volumetric modulated arc therapy. Manual alignment using CBCT-P and CBCT-FM was performed for each patient. Couch shifts were calculated and compared between methods in the left-right (x), superior-inferior (y), and anterior-posterior (z) directions. RESULTS: CBCT-P and CBCT-FM alignments were compared using 252 scans from the 16 patients. Mean displacement from zero was 2.4 ± 1.3, 1.7 ± 1.2, and 1.8 ± 1.1 mm for CBCT-P and 2.3 ± 1.3, 1.7 ± 1.1 and 1.8 ± 1.1 mm for CBCT-FM in the x, y and z directions, respectively. There was no difference in median displacement between CBCT-P and CBCT-FM; however, there was a significant positive correlation between CBCT-P- and CBCT-FM-based displacements in the x (r = 0.881; p < 0.001), y (r = 0.789; p < 0.001) and z (r = 0.856; p < 0.001) directions by linear regression analysis. Systematic deviations within each group were <1 mm; however, random and systematic errors were similar in the x and y directions but larger in the z direction. CONCLUSION: Our study demonstrated that CBCT-FM was not superior to CBCT-P for image-guided radiotherapy in prostate cancer patients.

Prognostic value of metabolic response measured by 18F-FDG-PET in oesophageal cancer patients treated with definitive chemoradiotherapy.

BACKGROUND: This study aimed to assess the efficacy of fluorine-18 fluorodeoxyglucose (F-FDG)-PET for predicting overall survival (OS) and disease-free survival (DFS) in oesophageal cancer patients after definitive chemoradiotherapy (CRT) and prognostic importance of metabolic response detected by post-treatment PET at least 3 months after completing CRT. MATERIALS AND METHODS: Data from 58 oesophageal cancer patients receiving definitive CRT were retrospectively analysed. Post-treatment F-FDG-PET was delivered at a median of 3.2 (range, 3.0-6.4) months after CRT. The impact of metabolic response determined by post-treatment F-FDG-PET, maximum post-treatment standardized uptake value (SUVmax) and percent SUV change (pretreatment to post-treatment) on survival was analysed. RESULTS: The median follow-up was 19.7 (range, 4.2-91.9) months for all patients and 28.2 (range, 13.7-91.9) months for survivors. The mean pretreatment and post-treatment SUVmax and the median percent SUV decrease were 18.6±6.4, 6.2±4.6 and -73% (+13 to -100%). Pretreatment SUVmax was higher in patients with locoregional or distant failure than in those without (P<0.001). Pretreatment SUVmax was lower in patients with a complete response (CR) than in those without a CR (P=0.006). Two-year OS and DFS were higher in patients with CR compared with those without CR (P<0.001). CR rates detected by post-treatment F-FDG-PET were lower in patients with lymph node metastases or longer tumours than in those with shorter tumours or no metastases. During multivariate analysis, post-treatment SUVmax was a significant predictor for OS, and post-treatment SUVmax, percent SUV decrease and tumour length were significant prognostic factors for DFS. CONCLUSION: Metabolic response assessed by post-treatment F-FDG-PET at least 3 months after CRT showed that post-treatment SUVmax and percent SUV change were important survival predictors.