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Leukotoxicity after moderately Hypofractionated radiotherapy versus conventionally fractionated dose escalated radiotherapy for localized prostate Cancer: a secondary analysis from a randomized study.

ABSTRACT: BACKGROUND:To compare WBC counts during treatment of localized prostate cancer with either conventionally fractionated (CF) or moderately hypofractionated (HYPO) radiotherapy. METHODS:Weekly blood test results were extracted from the charts of patients treated within a phase III study comparing HYPO to CF. In order to compare WBC counts at the same nominal dose in both arms and thus to tease out the effect of fractionation, for each recorded WBC value the corresponding cumulative total dose was extracted as well. WBC counts were binned according to percentiles of the delivered dose and three dose levels were identified at median doses of 16, 34.1 and 52?Gy, respectively. A General Linear Model based on mixed design Analysis Of Variance (ANOVA) was used to test variation of WBC counts between the two treatment arms. RESULTS:Out of 168 randomized patients, 140 (83.3%) had at least one observation for each one of the selected dose levels and were included in the analysis. Mean counts were lower in the CF than the HYPO arm at all selected dose levels, reaching a statistically significant difference at dose level #3 (5397/mm3 vs 6038/mm3 for CF and HYPO, respectively, p?=?0.004). The GLM model confirms that the impact of dose on WBC counts is significantly lower in the HYPO arm over the CF one (Greenhouse-Geisser test, p?=?0.04). Interestingly, while WBC counts tend to drop throughout all dose levels in the CF arm, this is the case only in the earlier part of treatment in the HYPO arm. CONCLUSION:This secondary analysis of a phase III study shows that dose fractionation is correlated to WBC drop during treatment of localized prostate cancer, favoring HYPO over CF.

SUBMITTER: Sanguineti G

PROVIDER: S-EPMC6352380 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Leukotoxicity after moderately Hypofractionated radiotherapy versus conventionally fractionated dose escalated radiotherapy for localized prostate Cancer: a secondary analysis from a randomized study.

Sanguineti Giuseppe G Giannarelli Diana D Petrongari Maria Grazia MG Arcangeli Stefano S Sangiovanni Angelo A Saracino Biancamaria B Farneti Alessia A Faiella Adriana A Conte Mario M Arcangeli Giorgio G

Radiation oncology (London, England) 20190130 1

<h4>Background</h4>To compare WBC counts during treatment of localized prostate cancer with either conventionally fractionated (CF) or moderately hypofractionated (HYPO) radiotherapy.<h4>Methods</h4>Weekly blood test results were extracted from the charts of patients treated within a phase III study comparing HYPO to CF. In order to compare WBC counts at the same nominal dose in both arms and thus to tease out the effect of fractionation, for each recorded WBC value the corresponding cumulative ...[more]

PMID: 30700317

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Project description:Purpose: Late gastrointestinal (GI) toxicity after radiotherapy for prostate cancer may have significant impact on the cancer survivor's quality of life. To date, little is known about local dose-effects after modern radiotherapy including hypofractionation. In the current study we related the local spatial distribution of radiation dose in the rectum to late patient-reported gastrointestinal (GI) toxicities for conventionally fractionated (CF) and hypofractionated (HF) modern radiotherapy in the randomized HYPRO trial. Material and Methods: Patients treated to 78 Gy in 2 Gy fractions (n = 298) or 64.6 Gy in 3.4 Gy fractions (n = 295) with available late toxicity questionnaires (n ? 2 within 1-5 years post-treatment) and available 3D planning data were eligible for this study. The majority received intensity modulated radiotherapy (IMRT). We calculated two types of dose surface maps: (1) the total delineated rectum with its central axis scaled to unity, and (2) the delineated rectum with a length of 7 cm along its central axis aligned on the prostate's half-height point (prostate-half). For each patient-reported GI symptom, dose difference maps were constructed by subtracting average co-registered EQD2 (equivalent dose in 2 Gy) dose maps of patients with and without the symptom of interest, separately for HF and CF. P-values were derived from permutation tests. We evaluated patient-reported moderate to severe GI symptoms. Results: Observed incidences of rectal bleeding and increased stool frequency were significantly higher in the HF group. For rectal bleeding (p = 0.016), mucus discharge (p = 0.015), and fecal incontinence (p = 0.001), significant local dose-effects were observed in HF patients but not in CF patients. For rectal pain, similar local dose-effects (p < 0.05) were observed in both groups. No significant local dose-effects were observed for increased stool frequency. Total rectum mapping vs. prostate-half mapping showed similar results. Conclusion: We demonstrated significant local dose-effect relationships for patient-reported late GI toxicity in patients treated with modern RT. HF patients were at higher risk for increased stool frequency and rectal bleeding, and showed the most pronounced local dose-effects in intermediate-high dose regions. These findings suggest that improvement of current treatment optimization protocols could lead to clinical benefit, in particular for HF treatment.

Dataset Information

Leukotoxicity after moderately Hypofractionated radiotherapy versus conventionally fractionated dose escalated radiotherapy for localized prostate Cancer: a secondary analysis from a randomized study.

Publications

Leukotoxicity after moderately Hypofractionated radiotherapy versus conventionally fractionated dose escalated radiotherapy for localized prostate Cancer: a secondary analysis from a randomized study.

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