Fulvestrant 500 mg Versus Anastrozole 1 mg for the First-Line Treatment of Advanced Breast Cancer: Overall Survival Analysis From the Phase II FIRST Study

PurposeTo compare overall survival (OS) for fulvestrant 500 mg versus anastrozole as first-line endocrine therapy for advanced breast cancer.Patients and MethodsThe Fulvestrant First-Line Study Comparing Endocrine Treatments (FIRST) was a phase II, randomized, open-label, multicenter trial. Postmenopausal women with estrogen receptor–positive, locally advanced/metastatic breast cancer who had no previous therapy for advanced disease received either fulvestrant 500 mg (days 0, 14, 28, and every 28 days thereafter) or anastrozole 1 mg (daily). The primary end point (clinical benefit rate [72.5% and 67.0%]) and a follow-up analysis (median time to progression [23.4 months and 13.1 months]) have been reported previously for fulvestrant 500 mg and anastrozole, respectively. Subsequently, the protocol was amended to assess OS by unadjusted log-rank test after approximately 65% of patients had died. Treatment effect on OS across several subgroups was examined. Tolerability was evaluated by adverse event monitoring.ResultsIn total, 205 patients were randomly assigned (fulvestrant 500 mg, n = 102; anastrozole, n = 103). At data cutoff, 61.8% (fulvestrant 500 mg, n = 63) and 71.8% (anastrozole, n = 74) had died. The hazard ratio (95% CI) for OS with fulvestrant 500 mg versus anastrozole was 0.70 (0.50 to 0.98; P = .04; median OS, 54.1 months v 48.4 months). Treatment effects seemed generally consistent across the subgroups analyzed. No new safety issues were observed.ConclusionThere are several limitations of this OS analysis, including that it was not planned in the original protocol but instead was added after time-to-progression results were analyzed, and that not all patients participated in additional OS follow-up. However, the present results suggest fulvestrant 500 mg extends OS versus anastrozole. This finding now awaits prospective confirmation in the larger phase III FALCON (Fulvestrant and Anastrozole Compared in Hormonal Therapy Naïve Advanced Breast Cancer) trial (ClinicalTrials.gov identifier: NCT01602380)

Estimating the number of colorectal cancer patients treated with anti-tumour therapy in 2015: the analysis of the Czech National Cancer Registry

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer (CRC) represents a serious health care problem in the Czech Republic, introducing a need for a prospective modelling of the incidence and prevalence rates. The prevalence of patients requiring anti-tumour therapy is also of great importance, as it is directly associated with planning of health care resources.</p> <p>Methods</p> <p>This work proposes a population-based model for the estimation of stage-specific prevalence of CRC patients who will require active anti-tumour therapy in a given year. Its applicability is documented on records of the Czech National Cancer Registry (CNCR), which is used to estimate the number of patients potentially treated with anti-tumour therapy in the Czech Republic in 2015.</p> <p>Results</p> <p>Several scenarios are adopted to cover the plausible development of the incidence and survival rates, and the probability of an anti-tumour therapy initiation. Based on the scenarios, the model predicts an increase in CRC prevalence from 13% to 30% in comparison with the situation in 2008. Moreover, the model predicts that 10,074 to 11,440 CRC patients will be indicated for anti-tumour therapy in the Czech Republic in 2015. Considering all patients with terminal cancer recurrence and all patients primarily diagnosed in stage IV, it is predicted that 3,485 to 4,469 CRC patients will be treated for the metastatic disease in 2015, which accounts for more than one third (34-40%) of all CRC patients treated this year.</p> <p>Conclusions</p> <p>A new model for the estimation of the number of CRC patients requiring active anti-tumour therapy is proposed in this paper. The model respects the clinical stage as the primary stratification factor and utilizes solely the population-based cancer registry data. Thus, no specific hospital data records are needed in the proposed approach. Regarding the short-term prediction of the CRC burden in the Czech Republic, the model confirms a continuous increase in the burden that must be accounted for in the future planning of health care in the Czech Republic.</p

Analysis of lung tumor motion in a large sample: patterns and factors influencing precise delineation of internal target volume

Purpose/Objective To evaluate lung tumor motion during respiration and to describe factors affecting the range and variability of motion in patients treated with stereotactic ablative radiation therapy. Methods and Materials Log file analysis from online respiratory tumor tracking was performed in 145 patients. Geometric tumor location in the lungs, tumor volume and origin (primary or metastatic), sex, and tumor motion amplitudes in the superior-inferior (SI), latero-lateral (LL), and anterior-posterior (AP) directions were recorded. Tumor motion variability during treatment was described using intrafraction/interfraction amplitude variability and tumor motion baseline changes. Tumor movement dependent on the tumor volume, position and origin, and sex were evaluated using statistical regression and correlation analysis. Results After analysis of >500 hours of data, the highest rates of motion amplitudes, intrafraction/interfraction variation, and tumor baseline changes were in the SI direction (6.0 ± 2.2 mm, 2.2 ± 1.8 mm, 1.1 ± 0.9 mm, and −0.1 ± 2.6 mm). The mean motion amplitudes in the lower/upper geometric halves of the lungs were significantly different (P15 mm were observed only in the lower geometric quarter of the lungs. Higher tumor motion amplitudes generated higher intrafraction variations (R=.86, P3 mm indicated tumors contacting mediastinal structures or parietal pleura. On univariate analysis, neither sex nor tumor origin (primary vs metastatic) was an independent predictive factor of different movement patterns. Metastatic lesions in women, but not men, showed significantly higher mean amplitudes (P=.03) and variability (primary, 2.7 mm; metastatic, 4.9 mm; P=.002) than primary tumors. Conclusion Online tracking showed significant irregularities in lung tumor movement during respiration. Motion amplitude was significantly lower in upper lobe tumors; higher interfraction amplitude variability indicated tumors in contact with mediastinal structures, although adhesion to parietal pleura did not necessarily reduce tumor motion amplitudes. The most variable lung tumors were metastatic lesions in women.Web of Science96475875

A single reference measurement can predict liver tumor motion during respiration

AimTo evaluate liver tumor motion and how well reference measurement predicts motion during treatment.Material and methodsThis retrospective study included 20 patients with colorectal cancer that had metastasized to the liver who were treated with stereotactic ablative radiotherapy. An online respiratory tumor tracking system was used. Tumor motion amplitudes in the superior-inferior (SI), latero-lateral (LL), and anterior-posterior (AP) directions were collected to generate patient-specific margins. Reference margins were generated as the mean motion and 95th percentile of motion from measurements recorded for different lengths of time (1, 3, and 5[[ce:hsp sp="0.25"/]]min). We analyzed the predictability of tumor motion in each axis, based on the reference measurement and intra-/interfraction motions.ResultsAbout 96,000 amplitudes were analyzed. The mean tumor motions were 9.9[[ce:hsp sp="0.25"/]]±[[ce:hsp sp="0.25"/]]4.2[[ce:hsp sp="0.25"/]]mm, 2.6[[ce:hsp sp="0.25"/]]±[[ce:hsp sp="0.25"/]]0.8[[ce:hsp sp="0.25"/]]mm, and 4.5[[ce:hsp sp="0.25"/]]±[[ce:hsp sp="0.25"/]]1.8[[ce:hsp sp="0.25"/]]mm in the SI, LL, and AP directions, respectively. The intrafraction variations were 3.5[[ce:hsp sp="0.25"/]]±[[ce:hsp sp="0.25"/]]1.8[[ce:hsp sp="0.25"/]]mm, 0.63[[ce:hsp sp="0.25"/]]±[[ce:hsp sp="0.25"/]]0.35[[ce:hsp sp="0.25"/]]mm, and 1.4[[ce:hsp sp="0.25"/]]±[[ce:hsp sp="0.25"/]]0.65[[ce:hsp sp="0.25"/]]mm for the SI, LL, and AP directions, respectively. The interfraction motion variations were 1.32[[ce:hsp sp="0.25"/]]±[[ce:hsp sp="0.25"/]]0.79[[ce:hsp sp="0.25"/]]mm, 0.31[[ce:hsp sp="0.25"/]]±[[ce:hsp sp="0.25"/]]0.23[[ce:hsp sp="0.25"/]]mm, and 0.68[[ce:hsp sp="0.25"/]]±[[ce:hsp sp="0.25"/]]0.62[[ce:hsp sp="0.25"/]]mm for the SI, LL, and AP directions, respectively. The Pearson's correlation coefficients for margins based on the reference measurement (mean motion or 95th percentile) and margins covering 95% of the motion during the whole treatment were 0.8–0.91, 0.57–0.7, and 0.77–0.82 in the SI, LL, and AP directions, respectively.ConclusionLiver tumor motion in the SI direction can be adequately represented by the mean tumor motion amplitude generated from a single 1[[ce:hsp sp="0.25"/]]min reference measurement. Longer reference measurements did not improve results for patients who were well-educated about the importance of regular breathing. Although the study was based on tumor tracking data, the results are useful for ITV delineation when tumor tracking is not available

A single reference measurement can predict liver tumor motion during respiration

Aim: To evaluate liver tumor motion and how well reference measurement predicts motion during treatment. Material and methods: This retrospective study included 20 patients with colorectal cancer that had metastasized to the liver who were treated with stereotactic ablative radiotherapy. An online respiratory tumor tracking system was used. Tumor motion amplitudes in the superior-inferior (SI), latero-lateral (LL), and anterior-posterior (AP) directions were collected to generate patient-specific margins. Reference margins were generated as the mean motion and 95th percentile of motion from measurements recorded for different lengths of time (1, 3, and 5 min). We analyzed the predictability of tumor motion in each axis, based on the reference measurement and intra-/interfraction motions. Results: About 96,000 amplitudes were analyzed. The mean tumor motions were 9.9 +/- 4.2 mm, 2.6 +/- 0.8 mm, and 4.5 +/- 1.8 mm in the SI, LL, and AP directions, respectively. The intrafraction variations were 3.5 +/- 1.8 mm, 0.63 +/- 0.35 mm, and 1.4 +/- 0.65 mm for the SI, LL, and AP directions, respectively. The interfraction motion variations were 1.32 +/- 0.79 mm, 0.31 +/- 0.23 mm, and 0.68 +/- 0.62 mm for the SI, LL, and AP directions, respectively. The Pear son's correlation coefficients for margins based on the reference measurement (mean motion or 95th percentile) and margins covering 95% of the motion during the whole treatment were 0.8-0.91, 0.57-0.7, and 0.77-0.82 in the SI, LL, and AP directions, respectively. Conclusion: Liver tumor motion in the SI direction can be adequately represented by the mean tumor motion amplitude generated from a single 1 min reference measurement. Longer reference measurements did not improve results for patients who were well-educated about the importance of regular breathing. Although the study was based on tumor tracking data, the results are useful for ITV delineation when tumor tracking is not available.Web of Science21328327

Chromoendoscopy to Detect Early Synchronous Second Primary Esophageal Carcinoma in Patients with Squamous Cell Carcinomas of the Head and Neck?

Objective. To evaluate the use of flexible esophagoscopy and chromoendoscopy with Lugol’s solution in the detection of early esophageal carcinomas (second primary carcinomas) in patients with squamous cell carcinoma of the head and neck (HNSCC). Methods. All patients with newly diagnosed HNSCC underwent office-based Lugol's chromoendoscopy. After flexible esophagoscopy with white light, 3.0% Lugol's iodine solution was sprayed over the entire esophageal mucosa. Areas with less-intense staining (LVLs) were evaluated and biopsies taken. Results. 132 patients with HNSCC were enrolled in this study. The most frequent primary tumors were oropharyngeal (49/132), tumors of the oral cavity (36/132), and larynx (35/132). The majority of subjects (107/132 patients, 81.1%) had advanced HNSCC carcinomas (stages III and IV). Multiple LVLs were discovered in 24 subjects (18.2%) and no LVLs in 108 (81.8%) subjects. Fifty-five LVL biopsy specimens were obtained and assessed. Squamous cell carcinomas were detected in two patients, peptic esophagitis in 11 patients, gastric heterotopic mucosa in two patients, hyperplasia in two patients, and low- and high-grade dysplasia in three patients. Conclusion. Although only two patients with synchronous primary carcinomas were found among the patients, esophagoscopy should be recommended after detection of HNSCC to exclude secondary esophageal carcinoma or dysplasia

Clinical Study Chromoendoscopy to Detect Early Synchronous Second Primary Esophageal Carcinoma in Patients with Squamous Cell Carcinomas of the Head and Neck?

Objective. To evaluate the use of flexible esophagoscopy and chromoendoscopy with Lugol&apos;s solution in the detection of early esophageal carcinomas (second primary carcinomas) in patients with squamous cell carcinoma of the head and neck (HNSCC). Methods. All patients with newly diagnosed HNSCC underwent office-based Lugol&apos;s chromoendoscopy. After flexible esophagoscopy with white light, 3.0% Lugol&apos;s iodine solution was sprayed over the entire esophageal mucosa. Areas with lessintense staining (LVLs) were evaluated and biopsies taken. Results. 132 patients with HNSCC were enrolled in this study. The most frequent primary tumors were oropharyngeal (49/132), tumors of the oral cavity (36/132), and larynx (35/132). The majority of subjects (107/132 patients, 81.1%) had advanced HNSCC carcinomas (stages III and IV). Multiple LVLs were discovered in 24 subjects (18.2%) and no LVLs in 108 (81.8%) subjects. Fifty-five LVL biopsy specimens were obtained and assessed. Squamous cell carcinomas were detected in two patients, peptic esophagitis in 11 patients, gastric heterotopic mucosa in two patients, hyperplasia in two patients, and low-and high-grade dysplasia in three patients. Conclusion. Although only two patients with synchronous primary carcinomas were found among the patients, esophagoscopy should be recommended after detection of HNSCC to exclude secondary esophageal carcinoma or dysplasia