Pelvic bone marrow dose-volume predictors of late lymphopenia following pelvic lymph node radiation therapy for prostate cancer.

BACKGROUND AND PURPOSE: Given the substantial lack of knowledge, we aimed to assess clinical/dosimetry predictors of late hematological toxicity on patients undergoing pelvic-nodes irradiation (PNI) for prostate cancer (PCa) within a prospective multi-institute study. MATERIALS AND METHODS: Clinical/dosimetry/blood test data were prospectively collected including lymphocytes count (ALC) at baseline, mid/end-PNI, 3/6 months and every 6 months up to 5-year after PNI. DVHs of the Body, ileum (BMILEUM), lumbosacral spine (BMLS), lower pelvis (BMPELVIS), and whole pelvis (BMTOT) were extracted. Current analysis focused on 2-year CTCAEv4.03 Grade ≥ 2 (G2+) lymphopenia (ALC < 800/µL). DVH parameters that better discriminate patients with/without toxicity were first identified. After data pre-processing to limit overfitting, a multi-variable logistic regression model combining DVH and clinical information was identified and internally validated by bootstrap. RESULTS: Complete data of 499 patients were available: 46 patients (9.2 %) experienced late G2+ lymphopenia. DVH parameters of BMLS/BMPELVIS/BMTOT and Body were associated to increased G2+ lymphopenia. The variables retained in the resulting model were ALC at baseline [HR = 0.997, 95 %CI 0.996-0.998, p < 0.0001], smoke (yes/no) [HR = 2.9, 95 %CI 1.25-6.76, p = 0.013] and BMLS-V ≥ 24 Gy (cc) [HR = 1.006, 95 %CI 1.002-1.011, p = 0.003]. When acute G3+ lymphopenia (yes/no) was considered, it was retained in the model [HR = 4.517, 95 %CI 1.954-10.441, p = 0.0004]. Performances of the models were relatively high (AUC = 0.87/0.88) and confirmed by validation. CONCLUSIONS: Two-year lymphopenia after PNI for PCa is largely modulated by baseline ALC, with an independent role of acute G3+ lymphopenia. BMLS-V24 was the best dosimetry predictor: constraints for BMTOT (V10Gy < 1520 cc, V20Gy < 1250 cc, V30Gy < 850 cc), and BMLS (V24y < 307 cc) were suggested to potentially reduce the risk.

Quality of Life Longitudinal Evaluation in Prostate Cancer Patients from Radiotherapy Start to 5 Years after IMRT-IGRT.

PURPOSE: The purpose of this study is to study the evolution of quality of life (QoL) in the first 5 years following Intensity-modulated radiation therapy (IMRT) for prostate cancer (PCa) and to determine possible associations with clinical/treatment data. MATERIAL AND METHODS: Patients were enrolled in a prospective multicentre observational trial in 2010-2014 and treated with conventional (74-80 Gy, 1.8-2 Gy/fr) or moderately hypofractionated IMRT (65-75.2 Gy, 2.2-2.7 Gy/fr). QoL was evaluated by means of EORTC QLQ-C30 at baseline, at radiation therapy (RT) end, and every 6 months up to 5 years after IMRT end. Fourteen QoL dimensions were investigated separately. The longitudinal evaluation of QoL was analysed by means of Analysis of variances (ANOVA) for multiple measures. RESULTS: A total of 391 patients with complete sets of questionnaires across 5 years were available. The longitudinal analysis showed a trend toward the significant worsening of QoL at RT end for global health, physical and role functioning, fatigue, appetite loss, diarrhoea, and pain. QoL worsening was recovered within 6 months from RT end, with the only exception being physical functioning. Based on ANOVA, the most impaired time point was RT end. QoL dimension analysis at this time indicated that acute Grade ≥ 2 gastrointestinal (GI) toxicity significantly impacted global health, physical and role functioning, fatigue, appetite loss, diarrhoea, and pain. Acute Grade ≥ 2 genitourinary (GU) toxicity resulted in lower role functioning and higher pain. Prophylactic lymph-nodal irradiation (WPRT) resulted in significantly lower QoL for global health, fatigue, appetite loss, and diarrhoea; lower pain with the use of neoadjuvant/concomitant hormonal therapy; and lower fatigue with the use of an anti-androgen. CONCLUSIONS: In this prospective, longitudinal, observational study, high radiation IMRT doses delivered for PCa led to a temporary worsening of QoL, which tended to be completely resolved at six months. Such transient worsening was mostly associated with acute GI/GU toxicity, WPRT, and higher prescription doses.

Worsening of 2-year patient-reported intestinal functionality after radiotherapy for prostate cancer including pelvic node irradiation.

BACKGROUND AND PURPOSE: To quantify patient-reported 2-year intestinal toxicity (IT) from pelvic nodal irradiation (PNI) for prostate cancer. The association between baseline/acute symptoms and 2-year worsening was investigated. MATERIALS AND METHODS: Patient-reported IT was prospectively assessed through the Inflammatory Bowel Disease Questionnaire (IBDQ), filled in at baseline, radiotherapy mid-point and end, at 3 and 6 months and every 6 months until 5 years. Two-year deterioration of IBDQ scores relative to the Bowel Domain was investigated for 400 patients with no severe baseline symptoms and with questionnaires available at baseline, 2 years, RT mid-point and/or end and at least three follow-ups between 3 and 18 months. The significance of the 2-year differences from baseline was tested. The association between baseline values and ΔAcute (the worst decline between baseline and RT mid-point/end) was investigated. RESULTS: In the IBDQ lower scores indicate worse symptoms. A significant (p < 0.0001) 2-year mean worsening, mostly in the range of -0.2/-0.4 points on a 1-7 scale, emerged excepting one question (IBDQ29, "nausea/feeling sick"). This decline was independent of treatment intent while baseline values were associated with 2-year absolute scores. The ΔAcute largely modulated 2-year worsening: patients with ΔAcute greater than the first quartile (Q1) and ΔAcute less or equal than Q1 showed no/minimal and highly significant (p < 0.0001) deterioration, respectively. Rectal incontinence, urgency, frequency and abdominal pain showed the largest mean changes (-0.5/-1): risk of severe worsening (deemed to be of clinical significance if ≤ 2) was 3-5 fold higher in the ΔAcute ≤ Q1 vs ΔAcute > Q1 group (p < 0.0001). CONCLUSION: A modest but significant deterioration of two-year patient-reported intestinal symptoms from PNI compared to baseline was found. Patients experiencing more severe acute symptoms are at higher risk of symptom persistence at 2 years, with a much larger prevalence of clinically significant symptoms.

Patient-reported persistent symptoms after radiotherapy and association with quality of life for prostate cancer survivors.

PURPOSE: To evaluate the persistence of symptoms after radiotherapy (RT) for localised prostate cancer (PCa) and the association with quality of life (QOL). MATERIALS AND METHODS: Prospective patient-reported outcome (PRO) from a multi-institutional study on PCa treated with radical RT (2010-2014) was analysed. Data was collected at baseline (BL) and follow-ups (FUPs) up to 5 years. Patients with BL and ≥3 late FUPs (≥6 months) were analysed. PRO was scored by means of the IPSS and ICIQ-SF (urinary), LENT-SOMA (gastrointestinal [GI]), and EORTC-C30 (pain, insomnia, fatigue, and QOL) questionnaires. Symptoms were defined 'persistent' if the median score over FUPs was ≥3 (urinary) or ≥2 (GI, pain, insomnia, and fatigue), and worse than BL. Different thresholds were chosen to have enough events for each symptom. QOL was linearly transformed on a continuous scale (0-100). Linear-mixed models were used to identify significant differences between groups with and without persistent symptoms including age, smoking status, previous abdominal surgery, and diabetes as confounders. Mean QOL differences between groups were evaluated longitudinally over FUPs. RESULTS: The analysis included 293 patients. Persistent urinary symptoms ranged from 2% (straining) to 12% (weak stream, and nocturia). Gastrointestinal symptoms ranged from 7% (rectal pain, and incontinence) to 30% (urgency). Proportions of pain, insomnia, and fatigue were 6, 13, and 18%. Significant QOL differences of small-to-medium clinical relevance were found for urinary incontinence, frequency, urgency, and nocturia. Among GI symptoms, rectal pain and incontinence showed small-to-medium differences. Fatigue was associated with the largest differences. CONCLUSIONS: The analysis showed that symptoms after RT for PCa occur with different persistence and their association with QOL varies in magnitude. A number of persistent urinary and GI symptoms showed differences in a comparable range. Urinary incontinence and frequency, rectal pain, and faecal incontinence more often had significant associations. Fatigue was also prevalent and associated with largely deteriorated QOL.

Gross tumour volume comparison in oropharynx carcinomas using different intelligent imaging software. A retrospective analysis.

PURPOSE: To compare gross tumour volume (GTV) in oropharynx carcinomas using different intelligent imaging software and to evaluate which method is more reliable for tumour volume definition in comparison with 3D ProSoma software. MATERIAL AND METHODS: We retrospectively studied 32 patients with histopathologically confirmed oropharynx carcinomas on dual-source computed tomography (CT) (all patients underwent multislice CT examination after applying 75 ml iodinated non-ionic contrast media). One radiologist calculated the tumour volume - manually measuring tumour length (L), width (W), and height (H) - and then calculated the tumour volume using the formula 0.5236 × L × W × H. The other radiologist used the syngo.CT-Liver-Analysis software to calculate the tumour volumes. Both volume measuring methods were compared with the 3D ProSoma software, which is used by radiotherapists to calculate tumour volumes. Graphpad Prism software was used for statistical data. RESULTS: syngo.CT-Liver-Analysis software for gross tumour volume determination has greater reliability than the standard manual method with Syngo Plaza in comparison with the 3D ProSoma software. CONCLUSIONS: syngo.CT-Liver-Analysis software is a reliable tool for GTV calculation, with a high correlation score, like that of radiotherapeutic 3D ProSoma software.