Machine learning-based automated planning for hippocampal avoidance prophylactic cranial irradiation

Purpose Design and evaluate a knowledge-based model using commercially available artificial intelligence tools for automated treatment planning to efficiently generate clinically acceptable hippocampal avoidance prophylactic cranial irradiation (HA-PCI) plans in patients with small-cell lung cancer. Materials and methods Data from 44 patients with different grades of head flexion (range 45°) were used as the training datasets. A Rapid Plan knowledge-based planning (KB) routine was applied for a prescription of 25 Gy in 10 fractions using two volumetric modulated arc therapy (VMAT) arcs. The 9 plans used to validate the initial model were added to generate a second version of the RP model (Hippo-MARv2). Automated plans (AP) were compared with manual plans (MP) according to the dose-volume objectives of the PREMER trial. Optimization time and model quality were assessed using 10 patients who were not included in the first 44 datasets. Results A 55% reduction in average optimization time was observed for AP compared to MP. (15 vs 33 min; p = 0.001).Statistically significant differences in favor of AP were found for D98% (22.6 vs 20.9 Gy), Homogeneity Index (17.6 vs 23.0) and Hippocampus D mean (11.0 vs 11.7 Gy). The AP met the proposed objectives without significant deviations, while in the case of the MP, significant deviations from the proposed target values were found in 2 cases. Conclusion The KB model allows automated planning for HA-PCI. Automation of radiotherapy planning improves efficiency, safety, and quality and could facilitate access to new techniques (AU)

Management of high-risk and post-operative non-metastatic prostate cancer in Catalonia: an expert Delphi consensus.

BACKGROUND: To reach a consensus on recommendations for the management of high-risk and post-operative non-metastatic prostate cancer by a group of Radiation Oncologists in Catalonia dedicated to prostate cancer. METHODS: A modified Delphi approach was employed to reach consensus on controversial topics in Radiation Oncology on high-risk non-metastatic (eight questions) and post-operative (eight questions) prostate cancer. An agreement of at least 75% was considered as consensus. The survey was electronically sent 6 weeks before an expert meeting where topics were reviewed and discussed. A second-round survey for the controversial questions only was sent and answered by participants after the meeting. RESULTS: After the first round of the survey, 19 experienced Radiation Oncologists attended the meeting and 74% fulfilled the second-round online questionnaire. An agreement of 9 of the 16 questions was accounted for the first round. After the meeting, an additional agreement was reached in 3 questions leading to a final consensus on 12 of the 16 questions. There are still controversial topics like the use of PET for staging of high-risk and post-operative non-metastatic prostate cancer and the optimal dose to the prostate bed in the salvage setting. CONCLUSION: This consensus contributes to establish recommendations and a framework to help in prostate cancer radiation therapy and pharmacological management in daily clinical practice of high-risk and post-operative non-metastatic prostate cancer.

Machine learning-based automated planning for hippocampal avoidance prophylactic cranial irradiation.

PURPOSE: Design and evaluate a knowledge-based model using commercially available artificial intelligence tools for automated treatment planning to efficiently generate clinically acceptable hippocampal avoidance prophylactic cranial irradiation (HA-PCI) plans in patients with small-cell lung cancer. MATERIALS AND METHODS: Data from 44 patients with different grades of head flexion (range 45°) were used as the training datasets. A Rapid Plan knowledge-based planning (KB) routine was applied for a prescription of 25 Gy in 10 fractions using two volumetric modulated arc therapy (VMAT) arcs. The 9 plans used to validate the initial model were added to generate a second version of the RP model (Hippo-MARv2). Automated plans (AP) were compared with manual plans (MP) according to the dose-volume objectives of the PREMER trial. Optimization time and model quality were assessed using 10 patients who were not included in the first 44 datasets. RESULTS: A 55% reduction in average optimization time was observed for AP compared to MP. (15 vs 33 min; p = 0.001).Statistically significant differences in favor of AP were found for D98% (22.6 vs 20.9 Gy), Homogeneity Index (17.6 vs 23.0) and Hippocampus D mean (11.0 vs 11.7 Gy). The AP met the proposed objectives without significant deviations, while in the case of the MP, significant deviations from the proposed target values were found in 2 cases. CONCLUSION: The KB model allows automated planning for HA-PCI. Automation of radiotherapy planning improves efficiency, safety, and quality and could facilitate access to new techniques.

Safety and Efficacy of Crizotinib in Combination with Temozolomide and Radiotherapy in Patients with Newly Diagnosed Glioblastoma: Phase Ib GEINO 1402 Trial.

BACKGROUND: MET-signaling and midkine (ALK ligand) promote glioma cell maintenance and resistance against anticancer therapies. ALK and c-MET inhibition with crizotinib have a preclinical therapeutic rationale to be tested in newly diagnosed GBM. METHODS: Eligible patients received crizotinib with standard radiotherapy (RT)/temozolomide (TMZ) followed by maintenance with crizotinib. The primary objective was to determine the recommended phase 2 dose (RP2D) in a 3 + 3 dose escalation (DE) strategy and safety evaluation in the expansion cohort (EC). Secondary objectives included progression-free (PFS) and overall survival (OS) and exploratory biomarker analysis. RESULTS: The study enrolled 38 patients. The median age was 52 years (33-76), 44% were male, 44% were MGMT methylated, and three patients had IDH1/2 mutation. In DE, DLTs were reported in 1/6 in the second cohort (250 mg/QD), declaring 250 mg/QD of crizotinib as the RP2D for the EC. In the EC, 9/25 patients (32%) presented grade ≥3 adverse events. The median follow up was 18.7 months (m) and the median PFS was 10.7 m (95% CI, 7.7-13.8), with a 6 m PFS and 12 m PFS of 71.5% and 38.8%, respectively. At the time of this analysis, 1 died without progression and 24 had progressed. The median OS was 22.6 m (95% CI, 14.1-31.1) with a 24 m OS of 44.5%. Molecular biomarkers showed no correlation with efficacy. CONCLUSIONS: The addition of crizotinib to standard RT and TMZ for newly diagnosed GBM was safe and the efficacy was encouraging, warranting prospective validation in an adequately powered, randomized controlled study.

Validation of 3D printing materials for high dose-rate brachytherapy using ionisation chamber and custom phantom.

Methods.Measurements were taken with the Exradin A20 (Standard Imaging) ionisation chamber, and the 'homemade' MARM phantom was made with the 3D Ultimaker 2+ printer using PLA material. The material used for validation was ABS Medical from Smart Materials 3D. The irradiation was undertaken with a192Ir source by means of Varian's GammaMed Plus iX HDR equipment. EBT3 films were used to run additional tests. We compared different measurements for PLA, ABS Medical, and water. Additional validation methods, described in the bibliography, were also compared.Results.The measurements with the ionisation chamber that we obtained using the MARM phantom with PLA and ABS within the clinically relevant range (0.5-1.5 cm) differ with respect to the measures in the water reference, by 2.3% and 0.94%, respectively.Discussion.The literature describes highly heterogeneous validation methods, complicating the performance of systematic reviews and comparisons between materials. Thus, creating a phantom represents a single effort that will quickly pay off. This system enables comparisons, ensuring that geometric conditions remain stable-something that is not always possible with radiochromic films. The use of a calibrated ionisation chamber in the corresponding energy range, combined with the 'homemade' MARM phantom applied according to the proposed methodology, allows a differentiation between the attenuation of the material itself and the drop in the dose due to distance.Conclusion.The validation method for 3D printing materials, using an ionisation chamber and the MARM PLA phantom, represents an accessible, standardisable solution for manufacturing brachytherapy applicators.

Is EAT-10 Useful to Assess Swallowing during the Chemo-Radiotherapy Phase in Patients with Head and Neck Cancer? A Pilot Study.

OBJECTIVE/HYPOTHESIS: The 10-item Eating-Assessment Tool (EAT-10) is a dysphagia screening test. In HNC patients, screening and diagnosis of dysphagia are not well-established. To determine the metrological properties of the EAT-10 compared with videofluoroscopy in non-surgical HNC-patients and to assess the relationship between EAT-10 scores and patients' self-reported symptoms. STUDY DESIGN: Prospective cohort study. METHODS: Forty-six HNC-patients recently diagnosed and referred to chemoradiotherapy (CRT). Main outcome was evidence of dysphagia according to EAT-10 score, self-perception on a Visual Analog Scale (VAS) of impaired swallowing, severity on the Penetration-Aspiration Scale (PAS), and the Functional Oral Intake Scale (FOIS). Patients were assessed at baseline, before-CRT, after-CRT, and at 3-month follow-up. RESULTS: A strong baseline correlation between EAT-10, VAS, and FOIS was observed. All 3 values decreased in weeks 6 to 9 after CRT initiation; a poor correlation of EAT-10 with VAS was observed at 3-month follow-up. A receiver operating characteristic curve determined new cut-off points (sensitivity/specificity) for safe swallowing: baseline 3 (86%, 77%); post-CRT, 15 (62.5%, 80%); and 3-month follow-up, 4 (83%, 75%). CONCLUSIONS: New safe-swallow EAT-10-points are suggested for this population during screening and the oncological follow-up. A poor correlation between EAT10-score and patient self-reported symptoms was observed at the end-RT and at 3-month follow-up, highlighting the need for an objective evaluation instrument.

Effects of prophylactic swallowing exercises on dysphagia and quality of life in patients with head and neck cancer receiving (chemo) radiotherapy: the Redyor study, a protocol for a randomized clinical trial.

BACKGROUND: Radiation-induced dysphagia is common in patients with head and neck cancer (HNC). Available evidence suggests that exercise therapy prior to oncological treatment could potentially improve deglutition and quality of life; however, a randomized clinical trial is needed to confirm this observation. METHODS/DESIGN: The Redyor study is a single-blind randomized clinical trial designed to compare the effect of prophylactic oropharyngeal exercises on quality of life and dysphagia of 52 patients with HNC referred to the Radiotherapy Department. The intervention will consist of respiratory muscle training (3 times/day, 5 days/week, 21 weeks) added to the standard swallow therapy. All patients will perform the same exercise intervention, but at different times: before chemoradiotherapy (CRT; early intervention group) or immediately after completing CRT (late intervention group). The main outcome will be change in dysphagia severity assessed with the Penetration-Aspiration Scale in videofluoroscopy study; quality of life will be assessed with the EORTC-QLQ-C30 and its Head and Neck Cancer Module (QLQ-H&N35) at 3, 6, and 12 months after completing CRT. DISCUSSION: This ongoing clinical trial, registered in 2016, is based on the hypothesis that undergoing a pre-radiotherapy rehabilitation (pre-habilitation) program will have greater benefits (less decrease in quality of life, less delay in swallowing parameters, and less severe dysphagia) compared to post-CRT rehabilitation. The main objective is to assess dysphagia severity in HNC patients; and secondly, to evaluate changes in dysphagia-related quality of life, and to determine the correlation between a clinical variable and instrumental parameters during this period. TRIAL REGISTRATION: NCT0209009911 .

Phase 2 Randomized Study of Radiation Therapy and 3-Year Androgen Deprivation With or Without Concurrent Weekly Docetaxel in High-Risk Localized Prostate Cancer Patients.

PURPOSE: Docetaxel improves survival in patients with metastatic prostate cancer. This randomized phase 2 trial aimed to assess the activity of weekly docetaxel with radiation therapy (RT) plus androgen deprivation in patients with high-risk localized prostate cancer. The study examined the benefit of 9 weekly docetaxel administrations to RT plus 3 years of luteinizing hormone-releasing hormone analogues. METHODS AND MATERIALS: A total of 132 patients were recruited for the study. Patients' characteristics included T3-T4 stage (81.1%), Gleason score ≥8 (77.3%), prostate-specific antigen level >20 ng/mL (28.9%), and pN+ (18.2%). All patients included in the trial received either the standard-of-care control arm with luteinizing hormone-releasing hormone analogues plus RT (arm A) or the experimental arm (RT + 9 weekly cycles of docetaxel + 3 years of androgen deprivation therapy, arm B). The primary objective was to achieve a high percentage of patients who were free of biochemical recurrence within 5 years of randomization. Secondary endpoints included biochemical recurrence-free survival (BRFS), progression-free survival (PFS), overall survival (OS), clinical response rate, biochemical response rate, and toxicity. RESULTS: No difference between the arms of the study was found in biochemical recurrence (93.4% at 60 months for arm A vs 85.3% for arm B; P = .3297). PFS at 60 months was 93.4% and 83.7% in arms A and B, respectively (P = .2532). Five-year survival was 93.3% (95% confidence interval, 83.1-97.45) in arm A versus 93.6% (83.8-97.55) in arm B; median PFS and OS have not been reached. Prostate-specific antigen level ≤0.2 ng/mL at 3 months after the end of treatment was seen in 81.25% of patients in arm A compared with 90.48% of patients in arm B (P = .2028). BRFS was not significantly different between treatment arms. Diarrhea was the main nonhematologic toxicity. Long-term follow-up has not yet been enough to meet median PFS and OS. CONCLUSIONS: Concurrent weekly docetaxel can be administered safely with standard doses of RT without a significant increase in the toxicity profile. No statistically significant differences for 5-year BRFS, PFS, and OS have been observed when docetaxel was added to conventional treatment.

Once-Weekly Hypofractionated Radiotherapy for Breast Cancer in Elderly Patients: Efficacy and Tolerance in 486 Patients.

PURPOSE: Radiation therapy is a key treatment of breast cancer. Elderly patients with associated diseases that modify their performance status do not tolerate long periods of daily irradiation. The objective of this study is to analyze the results of weekly hypofractionated treatment in these patients. MATERIAL AND METHODS: Between 1992 and 2016, we included 486 elderly patients presenting concomitant pathology or sociofamilial problems in which it was not feasible to propose conventional treatment. They were treated with conservative surgery or mastectomy and then adjuvant hypofractionated irradiation, administering 5 Gy or 6.25 Gy in 6 fractions, once a week (total dose 30-37.5 Gy) over 6 weeks. RESULTS: Breast cancer overall survival according to the Kaplan-Meier method at 5 years was 74.2% ± 2.3%; breast cancer disease-free survival was 90% ± 1.6%; local relapse-free survival was 96.5% ± 1% showing that patients die more from other causes and not from their neoplasia. Acute dermatitis was mild (75.6% of the patients grades I-III) and 30.6% had moderate chronic fibrosis. CONCLUSIONS: The once-weekly hypofractionated radiotherapy is a feasible and convenient option for elderly patients with breast cancer. It is a safe treatment modality with similar survival and local control results compared to standard fractionation, while the side effects are acceptable.

Relationship between radiation-induced apoptosis of T lymphocytes and chronic toxicity in patients with prostate cancer treated by radiation therapy: a prospective study.

PURPOSE: To assess the correlation of radiation-induced apoptosis in vitro of CD4 and CD8 T lymphocytes with late toxicity of prostate cancer patients treated with radiation therapy. METHODS AND MATERIALS: 214 patients were prospectively included in the study. Peripheral blood was drawn from patients before treatment and irradiated with 8 Gy. The percentage of CD4+ and CD8+ T lymphocytes that underwent radiation-induced apoptosis was assessed by flow cytometry. Toxicity and mortality were correlated in 198 cases with pretreatment apoptosis and clinical and biological variables by use of a Cox proportional hazards model. RESULTS: The mean percentage of CD4+ and CD8+ T lymphocyte radiation-induced apoptosis was 28.58% (±14.23) and 50.76% (±18.9), respectively. Genitourinary (GU) toxicity was experienced by 39.9% of patients, while gastrointestinal (GI) toxicity was experienced by 19.7%. The probability of development of GU toxicity was nearly doubled (hazard ratio [HR] 1.99, P=.014) in those patients in whom the percentage of in vitro radiation-induced apoptosis of CD4+ T-lymphocytes was ≤28.58%. It was also almost double in patients who received doses ≥50 Gy in 65% of the bladder volume (V65 ≥50) (HR 1.92, P=.048). No correlation was found between GI toxicity and any of the variables studied. The probability of death during follow-up, after adjustment for different variables, was 2.7 times higher in patients with a percentage of CD8+ T lymphocyte apoptosis ≤50.76% (P=.022). CONCLUSIONS: In conclusion, our study shows, in the largest prospective cohort of prostate cancer patients undergoing radiation therapy, that in vitro radiation-induced apoptosis of CD4+ T lymphocytes assessed before radiation therapy was associated with the probability of developing chronic GU toxicity. In addition, the radiation dose received in the urinary bladder (V65 ≥50) affected the occurrence of GU toxicity. Finally, we also demonstrate that radiation-induced apoptosis of CD8+ T lymphocytes was associated with overall survival, although larger series are needed to confirm this finding.

Five-year outcomes, cosmesis, and toxicity with 3-dimensional conformal external beam radiation therapy to deliver accelerated partial breast irradiation.

PURPOSE: To report the interim results from a study comparing the efficacy, toxicity, and cosmesis of breast-conserving treatment with accelerated partial breast irradiation (APBI) or whole breast irradiation (WBI) using 3-dimensional conformal external beam radiation therapy (3D-CRT). METHODS AND MATERIALS: 102 patients with early-stage breast cancer who underwent breast-conserving surgery were randomized to receive either WBI (n=51) or APBI (n=51). In the WBI arm, 48 Gy was delivered to the whole breast in daily fractions of 2 Gy, with or without additional 10 Gy to the tumor bed. In the APBI arm, patients received 37.5 Gy in 3.75 Gy per fraction delivered twice daily. Toxicity results were scored according to the Radiation Therapy Oncology Group Common Toxicity Criteria. Skin elasticity was measured using a dedicated device (Multi-Skin-Test-Center MC-750-B2, CKelectronic-GmbH). Cosmetic results were assessed by the physician and the patients as good/excellent, regular, or poor. RESULTS: The median follow-up time was 5 years. No local recurrences were observed. No significant differences in survival rates were found. APBI reduced acute side effects and radiation doses to healthy tissues compared with WBI (P<.01). Late skin toxicity was no worse than grade 2 in either group, without significant differences between the 2 groups. In the ipsilateral breast, the areas that received the highest doses (ie, the boost or quadrant) showed the greatest loss of elasticity. WBI resulted in a greater loss of elasticity in the high-dose area compared with APBI (P<.05). Physician assessment showed that >75% of patients in the APBI arm had excellent or good cosmesis, and these outcomes appear to be stable over time. The percentage of patients with excellent/good cosmetic results was similar in both groups. CONCLUSIONS: APBI delivered by 3D-CRT to the tumor bed for a selected group of early-stage breast cancer patients produces 5-year results similar to those achieved with conventional WBI.

Irradiación completa de la mama y sobreimpresión del lecho tumoral hipofraccionadas en el cáncer de mama: valoración de la toxicidad / Whole-breast and tumor boost hypofractionated irradiation in breast carcinoma: toxicity results

Introducción. Presentamos los resultados de tolerancia de la adición de sobreimpresión hipofraccionada después de irradiación global hipofraccionada de la mama. Material y método. Se incluyeron pacientes con cirugía conservadora y tratadas mediante hipofraccionamiento de 2,67Gy/día hasta 40Gy sobre la mama. La sobreimpresión del lecho tumoral se realizó a dosis de 16 o 8Gy según los criterios de riesgo para recaída local: tamaño tumoral, grado, márgenes o presencia de carcinoma ductal in situ, o nada en ausencia de dichos factores. Resultados. Se trataron 110 pacientes. Los grupos de riesgo se distribuyeron en alto, medio o bajo, con 51, 54 y 5 pacientes, respectivamente. Un 4,5% no presentaron toxicidad aguda. Las pacientes presentaron dermitis grado i o ii en el 38,2 y 47,3% de los casos, respectivamente. No se observaron diferencias en la toxicidad aguda dependiendo de la dosis de sobreimpresión. Tras un seguimiento medio de 2 años, en 79 casos (71,8%) no hubo cambios cutáneos crónicos. Apareció fibrosis leve en 24 pacientes (21,8%) y de grado ii en 7 pacientes. Conclusiones. La sobreimpresión hipofraccionada parece bien tolerada y las toxicidades aguda y crónica son leves. No parece haber impacto de la dosis total acumulada en la incidencia de fibrosis(AU)

Introduction. We present the results of adding a hypofractionated boost after whole-breast hypofractionated radiotherapy and report patient tolerance of this procedure. Material and method. Patients were included after conservative surgery and underwent adjuvant therapy. The whole breast was treated at 2.67Gy per fraction up to 40Gy. The boost was performed at different dose levels (16 or 8Gy) according to the presence of risk factors for local recurrence (tumor size, histologic grade, margin status or the presence of carcinoma in situ) or nothing in case of their absence. Results. A total of 110 patients were treated. The distribution into high-, middle- and low-risk groups was 51, 54 and 5 patients, respectively. There was no toxicity in 4.5% of the patients. Grade i or ii dermatitis was found in 38.2 and 47.3%, respectively. No differences were observed in acute dermatitis depending on boost doses. After a follow-up of 2 years, there were no chronic skin or subcutaneous changes in 79 patients (71.8%). Mild fibrosis occurred in 24 patients (21.8%) and grade ii fibrosis occurred in 7 patients. Conclusions. Hypofractionated boost seems to be well tolerated. Acute and chronic toxicities are mild. The cumulative dose does not seem to increase the incidence of fibrosis at the boost area compared with the whole breast(AU)

Predictive factors for overall quality of life in patients with advanced cancer.

OBJECTIVE: This study examined which domains/symptoms from the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 15 Palliative (QLQ-C15-PAL), an abbreviated version of the health-related EORTC QLQ-C30 questionnaire designed for palliative cancer patients, were predictive of overall quality of life (QOL) in advanced cancer patients. METHODS: Patients with advanced cancer from six countries completed the QLQ-C15-PAL at consultation and at one follow-up point. Univariate and multivariate regression analyses were conducted to determine the predictive value of the EORTC QLQ-C15-PAL functional/symptom scores for global QOL (question 15). RESULTS: Three hundred forty-nine patients completed the EORTC QLQ-C15-PAL at baseline. In the total patient sample, worse emotional functioning, pain, and appetite loss were the most significant predictive factors for worse QOL. In the subgroup of patients with bone metastases (n = 240), the domains mentioned above were also the most significant predictors, whereas in patients with brain metastases (n = 109), worse physical and emotional functioning most significantly predicted worse QOL. One-month follow-up in 267 patients revealed that the significant predictors changed somewhat over time. For example, in the total patient sample, physical functioning, fatigue, and appetite loss were significant predictors at the follow-up point. A sub-analysis of predictive factors affecting QOL by primary cancer (lung, breast, and prostate) was also conducted for the total patient sample. CONCLUSION: Deterioration of certain EORTC QLQ-C15-PAL functional/symptom scores significantly contributes to worse overall QOL. Special attention should be directed to managing factors most influential on overall QOL to ensure optimal management of advanced cancer patients.

Long-term results and prognostic factors of patients with cervical carcinoma treated with concurrent chemoradiotherapy.

AIMS AND BACKGROUND: To evaluate the predictive factors of recurrence in cervical cancer treated with radical radiochemotherapy. METHODS: A retrospective analysis of 56 women was performed. Response was assessed using the RECIST response. Overall survival and disease-free survival curves were estimated by the Kaplan-Meier method and the Cox proportional hazards model was used to analyse predictors of recurrence. RESULTS: Local recurrence was documented in 16 patients and distant metastases in 15. The Kaplan-Meier survival probabilities were 95.1 ± 6.4% at 3 years and 80.4 ± 13.1% at 5 years and the Kaplan-Meier curve values for disease-free survival were 60.3 ± 14.3% at 3 years and 53.0 ± 15.7% at 5 years. Thirty-five patients were alive and 21 patients died, 19 from metastatic disease and 2 from other causes. Complete response after chemoradiation therapy, squamous cell carcinoma and tumour size ≤ 4 cm were significantly associated with outcome. In the Cox regression model, tumour size > 4 cm (hazard ratio 7.48; 95% CI 2.71-20.6; p < 0.001) and partial response (hazard ratio 7.09; 95% CI 2.82-17.8; p < 0.001) were predictive factors for disease-free survival and partial response (hazard ratio 3.7; 95% CI 1.3-10.1; p < 0.001) and non-squamous cell carcinoma (hazard ratio 3.5; 95% CI 1.2-9.7; p < 0.001) were predictive factors for overall survival. CONCLUSIONS: Non-squamous histology and partial response were independent prognostic factors for overall survival and tumour size and partial response were independent prognostic variables for 5-year disease survival.

18F-FDG PET definition of gross tumor volume for radiotherapy of lung cancer: is the tumor uptake value-based approach appropriate for lymph node delineation?

PURPOSE: Positron emission tomography (PET) with the glucose analogue [18F] fluoro-2-deoxy-D-glucose ((18)F-FDG-PET) has been used in radiation treatment planning for non-small-cell carcinoma. To date, lymph nodes have been contoured according to the uptake of the tumor. This prospective study was performed to evaluate if nodal volume delineates according to FDG uptake within the primary tumor (PET-GTVnt) is suitable for nodal target volume delineation or if individualized nodal FDG uptake measure (PET-GTVnn) is necessary to better nodal target definition. METHODS AND MATERIALS: Forty cases, who underwent a diagnostic (18)F-FDG PET/computed tomography (CT) scan, were included. Two PET-based GTVs for each lymph node were contoured and compared. First, we used an isocontour of 40% of the maximum tumor uptake (PET-GTVnt). Second, an isocontour of 40% of the maximum uptake of each node (PET-GTVnn) was employed. To avoid interobserver variability, this was carried out by the same radiation oncologist. Afterwards, the difference between both lymph node volumes was plotted against the ratio of the maximum uptakes (I(n)/I(t)) in a linear regression analysis. RESULTS: Compared with CT-based lymph node volume (CT-GTVn), the intraclass correlation coefficient of PET-GTVnn was higher than the coefficient of PET-GTVnt (p < 0.001). All cases could be divided into four groups: undetected (17.5%), detected but overestimated (10%), detected but underestimated (35%), and correctly detected (37.5%). CONCLUSIONS: If a method of automatic delineation shall be applied, this method must be applied to every lesion separately. However, to facilitate the delineation in daily practice, when I(n)/I(t) is ≤25%, lymph nodes could be delineated in accordance with tumor uptake, keeping an absolute difference in radii <5 mm.

Phase II study of vinorelbine and estramustine in combination with conformational radiotherapy for patients with high-risk prostate cancer.

PURPOSE: To evaluate the efficacy and safety profile of vinorelbine and estramustine in combination with three-dimensional conformational radiotherapy (3D-CRT) in patients with localized high-risk prostate cancer. METHODS AND MATERIALS: Fifty patients received estramustine, 600 mg/m(2) daily, and vinorelbine, 25 mg/m(2), on days 1 and 8 of a 21-day cycle for three cycles in combination with 8 weeks of 3D-CRT (total dose of 70.2 gray [Gy] at 1.8-Gy fractions or 70 Gy at 2.0-Gy fractions). Additionally, patients received luteinizing hormone-releasing hormone analogs for 3 years. RESULTS: All patients were evaluated for response and toxicity. Progression-free survival at 5 years was 72% (95% confidence interval [CI]: 52-86). All patients who relapsed had only biochemical relapse. The most frequent severe toxicities were cystitis (16% of patients), leucopenia (10% of patients), diarrhea (10% of patients), neutropenia (8% of patients), and proctitis (8% of patients). Six patients (12%) did not complete study treatment due to the patient's decision (n = 1) and to adverse events such as hepatotoxicity, proctitis, paralytic ileus, and acute myocardial infarction. CONCLUSIONS: Vinorelbine and estramustine in combination with 3D-CRT is a safe and effective regimen for patients with localized high-risk prostate cancer. A randomized trial is needed to determine whether the results of this regimen are an improvement over the results obtained with radiotherapy and androgen ablation.

Impact of PSA implementation and combined radiation and hormonal therapy (RT+HT) on outcome of prostate cancer patients.

Advances in the diagnosis and management of prostate cancer have been associated with changes in clinico-epidemiological characteristics and cancer-specific mortality. Secular trends of prostate cancer patients and its correlation with PSA implementation and the introduction of combined radiation and hormonal therapy (RT+HT) were assessed in a cohort of 910 cancer patients with histologically confirmed prostate cancer diagnosed between 1992 and 2005, and included in a hospital-based database. Relative survival before and after 1999 (when RT+HT for locally advanced disease was introduced) was compared. The mean age at diagnosis decreased from 72.9 years in 1992-1996 to 68.7 in 2003-2005 and the median PSA from 34 to 8 ng/ml. In patients with stages II and III, there was an increase in the indication of RT with or without HT and a decrease in the indication of surgery (from 87.5% to 44.2%). The overall relative 5-year survival increased from 67.3% (95% CI 60.2-75.2) to 92.9% (95% CI 87.3-98.9). The same trend in stage II and stage III cancer patients was found. There was an increase in survival coincidentally with a shift towards lower stages and PSA levels at presentation. Besides other factors, changes in death rates since 1999 could be explained by secular variations in the treatment of the disease, particularly the implementation of RT+HT in intermediate and high-risk locally advanced prostate cancer.

Predictors of acute esophagitis in lung cancer patients treated with concurrent three-dimensional conformal radiotherapy and chemotherapy.

PURPOSE: To evaluate the risk factors for acute esophagitis (AET) in lung cancer patients treated with concurrent 3D-CRT and chemotherapy. METHODS AND MATERIALS: Data from 100 patients treated with concurrent chemoradiotherapy with a mean dose of 62.05 +/- 4.64 Gy were prospectively evaluated. Esophageal toxicity was graded according to criteria of the Radiation Therapy Oncology Group. The following dosimetric parameters were analyzed: length and volume of esophagus in treatment field, percentage of esophagus volume treated to >or=10, >or=20, >or=30, >or=35, >or=40, >or=45, >or=50, >or=55, and >or=60 Gy, and the maximum (D(max)) and mean doses (D(mean)) delivered to the esophagus. Also, we developed an esophagitis index (EI) to account the esophagitis grades over treatment time. RESULTS: A total of 59 patients developed AET (Grade 1, 26 patients; Grade 2, 29 patients; and Grade 3, 4 patients). V50 was associated with AET duration (p = 0.017), AET Grade 1 duration (p = 0.016), maximum analgesia (p = 0.019), esophagitis index score (p = 0.024), and AET Grade >or=1 (p = 0.058). If V50 is <30% there is a 47.3% risk of AET Grade >or=1, which increases to 73.3% if V50 is >or=30% (p = 0.008). The predictive abilities of models (sensitivity and specificity) were calculated by receiver operating characeristic curves. CONCLUSIONS: According to the receiver operating characeristic curve analysis, the 30% of esophageal volume receiving >or=50 Gy was the most statistically significant factor associated with AET Grade >or=1 and maximum analgesia (A(max)). There was an association with AET Grade >or=2 but it did not achieve statistical significance (p = 0.076).

Prevention of radiochemotherapy-induced esophagitis with glutamine: results of a pilot study.

PURPOSE: To assess the usefulness of oral glutamine to prevent radiochemotherapy-induced esophagitis in patients with lung cancer, and to determine the dosimetric parameter predictive of esophagitis. METHODS AND MATERIALS: Seventy-five patients were enrolled; 34.7% received sequential radiochemotherapy, and 65.3% received concomitant radiochemotherapy. Every patient received prophylactic glutamine powder in doses of 10 g/8 h. Prescribed radiation doses were 45-50 Gy to planning target volume (PTV)1 (gross tumor volume plus wide margins) and 65-70 Gy to PTV2 (reduced margins). The primary endpoint was the incidence of Grade 2 or greater acute esophagitis. RESULTS: No patient experienced glutamine intolerance or glutamine-related toxicity. Seventy-three percent of patients who received sequential chemotherapy and 49% of those who received concomitant chemotherapy did not present any form of esophagitis. V50 was the dosimetric parameter with better correlation between esophagitis and its duration. A V50 of or=2, which increased to 71% with a V50 of >30% (p = 0.0009). CONCLUSIONS: The use of oral glutamine may have an important role in the prevention of esophageal complications of concomitant radiochemotherapy in lung cancer patients. However, randomized trials are needed to corroborate that effect. V50 is the dosimetric parameter with better correlation with esophagitis grade and duration.