The value of metabolic parameters and textural analysis in predicting prognosis in locally advanced cervical cancer treated with chemoradiotherapy.

OBJECTIVE: The aim of the study was to assess the impact of clinical and metabolic parameters derived from 18F-FDG PET/CT (positron emission tomography-computed tomography) in patients with locally advanced cervical cancer (LACC) on prognosis. METHODS: Patients with LACC of stage IB2-IVA treated by primary radiochemotherapy followed by brachytherapy were enrolled in this retrospective study. Indexes derived from standardized uptake value (SUV), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and textural features of the primary tumor were measured for each patient. Overall survival (OS) and recurrence-free survival (RFS) rates were calculated according to Kaplan-Meier and survival curves were compared using the log-rank test. Uni- and multivariate analyses were performed using the Cox regression model. RESULTS: A total of 116 patients were included. Median follow-up was 58 months (range: 1-129). A total of 36 (31%) patients died. Five-year OS and RFS rates were 69 and 60%, respectively. Univariate analyses indicated that FIGO stage, the presence of hydronephrosis, high CYFRA 21.1 levels, and textural features had a significant impact on OS and RFS. MTV as well as SCC-Ag concentration were also significantly associated with OS. On multivariate analysis, the presence of hydronephrosis, CYFRA 21.1, and sphericity were independent prognostics factors for OS and RFS. Also, SCC-Ag level, MTV, and GLZLM (gray-level zone length matrix) ZLNU (zone length non-uniformity) were significantly associated with OS. CONCLUSION: Classical prognostic factors and tumor heterogeneity on pretreatment PET/CT were significantly associated with prognosis in patients with LACC.

Postreatment squamous cell carcinoma antigen as a survival prognostic factor in patients with locally advanced cervical cancer. A Spanish multicenter study. The SEGO Spain-GOG group.

OBJECTIVE: To evaluate the clinical value of postreatment plasmatic levels of the squamous cell carcinoma antigen (SCC-Ag) as a survival independent prognostic factor in patients with LACC. METHODS: Retrospective, multicenter study including LACC patients (FIGO 2009 stages IB2, IIA2-IVA) managed at the Gynecology Oncological Units corresponding to eight reference hospitals in Spain between 2000 and 2016. Receiver operating characteristic (ROC) curve analysis was used to determine the cut-off values of postreatment SCC-Ag levels in prediction of survival. Survival curves were calculated by using the Kaplan-Meier method and were compared with the log-rank test. Cox models were used to analyze different factors in terms of their prognosis predictive value. RESULTS: The study included 447 patients with a median follow-up time of 53 months (IQR 26-101) and median pre- and postreatment SCC-Ag levels of 3.4 ng/ml (IQR 1.2-11) and 0.8 ng/ml (IQR 0.5-1.2), respectively. The cut-off level of pretreatment SCC-Ag was 11.75 ng/ml (sensibility 37.5%; specificity 80.5%) and that of postreatment SCC-Ag was 1.24 ng/ml (sensibility 34.6%; specificity 83.1%). In a multivariate Cox regression analysis, factors that were independent predictors of OS were: FIGO stage (HR 2.12; 95%CI 1.18-3.8; p = 0.011), paraaortic lymph node involvement (HR 3.56; 95%CI 2.04-6.2; p < 0.0001), postreatment SCC-Ag level ≥ 1.2 ng/ml (HR 1.95; 95%CI 1.11-3.44; p = 0.02) and incomplete response to treatment (HR 4.5; 95%CI 2.5-8.11; p < 0.0001). CONCLUSION: Postreatment plasmatic SCC-Ag level ≥ 1.2 ng/ml was an independent risk factor for the survival of patients with LACC. Further factors influencing survival included: paraaortic lymph node involvement, advanced disease and poor response to concomitant chemoradiotherapy.

Management of interruptions in radiotherapy treatments: Adaptive implementation in high workload sites.

Owing to predictable or unpredictable causes, interruptions may arise during therapy. On average, the extension of fractionated radiotherapy treatments is prone to be delayed by several weeks and interruptions can come up extending overall treatment time (OTT). Clonogenic cells of aggressive tumors might benefit from this situation, modifying local control (LC). Preserving treatment quality in radiotherapy is an essential issue for the treatment outcome, and our institution is increasingly concerned about this line of work. Establishing some objective criteria to schedule patients that have suffered interruptions along their treatments is of capital importance and not a trivial issue. Publications strongly encourage departments to minimize the effect of lag periods during treatments. Therefore, in July 2017, our facility implemented the so called 'Protocol to Manage Interruptions in Radiotherapy', based on a scoring system for patient categorization that considers not only histology but also associated comorbidity and sequence of the therapy.

Assessment of radiobiological metrics applied to patient-specific QA process of VMAT prostate treatments.

VMAT is a powerful technique to deliver hypofractionated prostate treatments. The lack of correlations between usual 2D pretreatment QA results and the clinical impact of possible mistakes has allowed the development of 3D verification systems. Dose determination on patient anatomy has provided clinical predictive capability to patient-specific QA process. Dose-volume metrics, as evaluation criteria, should be replaced or complemented by radiobiological indices. These metrics can be incorporated into individualized QA extracting the information for response parameters (gEUD, TCP, NTCP) from DVHs. The aim of this study is to assess the role of two 3D verification systems dealing with radiobiological metrics applied to a prostate VMAT QA program. Radiobiological calculations were performed for AAPM TG-166 test cases. Maximum differences were 9.3% for gEUD, -1.3% for TCP, and 5.3% for NTCP calculations. Gamma tests and DVH-based comparisons were carried out for both systems in order to assess their performance in 3D dose determination for prostate treatments (high-, intermediate-, and low-risk, as well as prostate bed patients). Mean gamma passing rates for all structures were bet-ter than 92.0% and 99.1% for both 2%/2 mm and 3%/3 mm criteria. Maximum discrepancies were (2.4% ± 0.8%) and (6.2% ± 1.3%) for targets and normal tis-sues, respectively. Values for gEUD, TCP, and NTCP were extracted from TPS and compared to the results obtained with the two systems. Three models were used for TCP calculations (Poisson, sigmoidal, and Niemierko) and two models for NTCP determinations (LKB and Niemierko). The maximum mean difference for gEUD calculations was (4.7% ± 1.3%); for TCP, the maximum discrepancy was (-2.4% ± 1.1%); and NTCP comparisons led to a maximum deviation of (1.5% ± 0.5%). The potential usefulness of biological metrics in patient-specific QA has been explored. Both systems have been successfully assessed as potential tools for evaluating the clinical outcome of a radiotherapy treatment in the scope of pretreatment QA.

Cisplatin-based radiochemotherapy improves the negative prognosis of c-erbB-2 overexpressing advanced cervical cancer.

OBJECTIVES: To determine the impact of c-erb-B2 overexpression on disease-free survival (DFS) and local relapse in patients with advanced cervical cancer (CC) receiving concurrent chemoradiotherapy treatment. METHODS: A total of 136 patients with advanced CC (FIGO stage: IB2-IIA [12]; IIB [34]; IIIB [71]; IVA [19]; including both epidermoid [86] and adenocarcinoma [14]) were analyzed to determine c-erb-B2 levels by immunohistochemistry (c-erb-B2 antibody; Dako, Glostrup, Denmark). Only c-erb-B2+++ biopsies were considered positive. All patients received pelvic radiotherapy, brachytherapy, and concurrent chemotherapy with 2 different regimens: 48 patients were treated with tegafur (800 mg/d orally) and 88 with tegafur (same doses) plus 5 cycles of weekly cisplatin 40 mg/m/wk intravenously. RESULTS: A total of 32 (23.5%) biopsies were considered c-erb-B2-positive. Three-year and 5-year DFS were 61% and 58% for c-erb-B2-negative patients and 36% and 36% for c-erB2-positive patients, respectively (P = 0.02). Patients were stratified in 4 groups according to their c-erb-B2 status and whether they received cisplatin. The group of patients with c-erb-B2 overexpression that did not receive platinum treatment had a higher rate of pelvic relapse (P < 0.0001), associated with a decreased DFS (P = 0.0014). CONCLUSIONS: c-erb-B2 overexpression may imply a poor prognosis for patients with advanced CC. Treatment with cisplatin-based radiochemotherapy improved outcome in these patients.

Negative prognostic impact of the coexpression of epidermal growth factor receptor and c-erbB-2 in locally advanced cervical cancer.

OBJECTIVE: The objective was to determine the impact of the coexpression of epidermal growth factor receptor (EGFR) and tumor marker c-erbB-2 on disease-free survival (DFS) and pelvic relapse-free survival (PRFS) in patients with locally advanced cervical cancer (LACC) receiving concurrent chemoradiotherapy. METHODS: The expression of EGFR and c-erbB-2 was assessed by immunohistochemistry, which was centralized and blinded to outcome. Univariate and multivariate analyses were used to evaluate the impact of EGFR and c-erbB-2 on DFS and PRFS. RESULTS: 170 patients with LACC were included and received concurrent chemoradiotherapy. 25 (15%) biopsies were considered EGFR and c-erbB-2 positive; 100 (59%) were either EGFR or c-erbB-2 positive, and 45 (26%) were EGFR and c-erbB-2 negative. The 3- and 5-year DFS was 39% each for EGFR- and c-erbB-2-positive patients, 54 and 49%, respectively, for EGFR- or c-erbB-2-positive patients, and 76 and 72%, respectively, for EGFR- and c-erbB-2-negative patients (p = 0.006). EGFR- and c-erbB-2-positive tumors were significantly associated with a decrease in PRFS (hazard ratio, HR, 3.99; 95% confidence interval, CI, 1.44-11.05, p = 0.007), and DFS (HR 2.9; 95% CI, 1.26-6.66, p = 0.01). CONCLUSION: Patients with LACC coexpressing EGFR and c-erbB-2, and treated with concurrent chemoradiotherapy, had a worse clinical prognosis with shorter DFS and PRFS.

Dural Plasmacytoma with Meningeal Myelomatosis in a Patient with Multiple Myeloma.

Here, we describe the case of a 66-year-old male diagnosed with multiple myeloma who presented with generalized tonic-clonic seizures. Magnetic resonance imaging demonstrated a right solid extra-axial parieto-occipital lesion with typical characteristics of meningeal myelomatosis. Biopsy was performed, which diagnosed a dural plasmacytoma. Because of this, we started concomitant therapy with radiotherapy and lenalidomide, but the patient has a poor response to treatment and died few weeks after its initiation. Myelomatous involvement of the dura mater is a rare occurrence, given that only few cases were reported in the English literature. This presentation confers an ominous prognosis and must be a suspect diagnosis in patients diagnosed with multiple myeloma presenting neurological symptoms.

Long-term changes in pulmonary function after incidental lung irradiation for breast cancer: a prospective study with 7-year follow-up.

PURPOSE: To evaluate late pulmonary function changes after incidental pulmonary irradiation for breast cancer. METHODS AND MATERIALS: Forty-three consecutive female patients diagnosed with breast carcinoma and treated with postoperative radiation therapy (RT) at the same dose (50 Gy) and fractionation (2 Gy/fraction, 5 days/week) were enrolled. Pulmonary function tests (PFT) and ventilation/perfusion scans were performed before RT and 6, 12, 24, and 84 months afterward. RESULTS: Forty-one patients, mean age 55 years, were eligible for the analysis. No differences were found in the baseline PFT values for age, smoking status and previous chemotherapy; women undergoing mastectomy showed baseline spirometric PFT values lower than did women treated with conservative surgery. The mean pulmonary dose was 10.9 Gy, being higher in women who also received lymph node RT (15.8 vs 8.6, P<.01). Only 1 patient experienced symptomatic pneumonitis. All PFT values showed a reduction at 6 months. From then on, the forced vital capacity and forced expiratory volume in 1 second began their recovery until reaching, and even exceeding, their baseline values at 7 years. Diffusing capacity of the lungs for carbon monoxide and ventilation/perfusion scans continued to reduce for 24 months and then partially recovered their baseline values (-3.5%, -3.8%, and -5.5%, respectively). Only the percentage difference at 7 years in the ventilation scan correlated with the dosimetric parameters studied. Other variables, such as age, smoking status, previous chemotherapy, and concomitant tamoxifen showed no significant relation with changes in PFT (ΔPFT) values at 7 years. CONCLUSIONS: The study of reproducible subclinical parameters, such as PFT values, shows how their figures decrease in the first 2 years but practically recover their baseline values in the long term. The extent of the reduction in PFT values was small, and there was no clear association with several dosimetric and clinical parameters.

Impact of epidermal growth factor receptor expression on disease-free survival and rate of pelvic relapse in patients with advanced cancer of the cervix treated with chemoradiotherapy.

OBJECTIVES: To determine the impact of the expression of epidermal growth factor receptor (EGFR) on disease-free survival (DFS) and on pelvic relapse in patients with advanced cancer of the cervix receiving concurrent chemoradiotherapy. METHODS: In 112 consecutive patients with advanced cancer of the cervix (11 stage IB2-IIA, 25 IIB, 63 IIIB, 13 IVA) treated with chemoradiotherapy between December 1994 and September 2004, the expression of EGFR using histoimmunochemistry was measured and used in univariate and multivariate analysis, along with variables such as age, International Federation of Gynecology and Obstetrics Staging System for Epithelial Ovarian Cancer (FIGO) stage, histology, Eastern Cooperative Oncology Group (ECOG), tumor size, and ganglia involvement diagnosed with computerized axial tomography, treatment with cisplatin to evaluate its impact on DFS and pelvic relapse. RESULTS: Of the 112 biopsies, 32 (28.6%) were negative or slightly positive (EGFR±) and 80 (71.4%) were moderate or intensely positive (EGFR++/+++). The overexpression of EGFR (++/+++) was significantly associated with an epidermoid histology (P < 0.0001), with a higher rate of pelvis relapse and a decreased DFS (hazard ratio [HR]: 2.31 [1.08-4.96]; P = 0.03). Overall, treatment with cisplatin increased DFS (HR: 0.51 [0.26-0.97]; P = 0.04). CONCLUSIONS: Patients with tumors of the cervix and overexpression of the EGFR++/+++ show a higher probability of pelvic relapses and a decreased disease-free survival. The poor prognosis of these tumors may be a consequence of an increase in radio-resistance.