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Background: The other side of radiotherapy (RT), in addition to the cytotoxic effect, is the ability to modulate the immune system in terms of activation or suppression, also depending on the dose and fractionation delivered. This immune RT effect can be detected both locally in the irradiated tumor site and in the peripheral blood. The aim of this study was to assess the consequence of pelvic irradiation on peripheral immune cells and cytokine secretions in localized prostate cancer (PC) patients undergoing pelvic irradiation with a simultaneous moderately hypofractionated prostate/prostate bed boost by Volumetric Modulated Arc Therapy (VMAT). Furthermore, we analyzed whether there was a correlation between these peripheral immune parameters and acute and late genitourinary (GU) and gastrointestinal (GI) toxicity. Methods: Thirty-eight PC patients were treated with pelvis irradiation (dose per fraction 1.8 Gy) and simultaneous hypofractionated (median dose per fraction: 2.7 Gy) prostate/prostate bed boost. A longitudinal analysis was performed for 12 months on peripheral blood to assess changes in 9 different lymphocyte subpopulations by flow cytometry and 10 circulating cytokines by Multiplex Luminex assay and ELISA. Results: Our analysis revealed that basal IFN-γ serum values were significantly lower in the definitive (curative intent for patients with prostate) patient group respect to the post-operative one. All the lymphocyte subsets and IFN-α, IFN-β and Il-2 peripheral concentrations displayed significant variations between the different time points considered. The immune cell population that suffers the greatest RT toxicity in the blood was B lymphocyte. We found an interesting correlation between basal TGF-β1 and late GU toxicity. In particular, TGF-β1 concentrations before RT were significantly higher in patients that experienced grade 2-3 of late GU toxicity, respect to grade 0-1. Exploring possible correlations between some clinical/biological findings and radiation planning parameters, we found no statistical significance. Conclusions: Our study analyzed, in the context of hypofractionated radiotherapy in prostate cancer, different parameters of the peripheral immune system. We have highlighted longitudinally the peripheral behavior of the different lymphocyte subpopulations and of a group of 10 cytokines during the first year after RT. One of the analyzed cytokines, such as TGF-β1, has proven to be promising predictive factor of severe late GU toxicity. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) is an important therapeutic option in patients with localized prostate cancer (PC). Unfortunately, radiation treatment causes a decrease in peripheral lymphocytes and, consequently, influences the patients' immune status. Our aim was to study changes in peripheral blood immune cell subpopulations after RT and during 6 months' follow-up in 2 groups of PC patients irradiated with different techniques and dose fractions with curative intent. We also investigated the presence of correlation between immune cell modulation and genitourinary or gastrointestinal toxicity. We enrolled 44 patients treated with curative RT (RapidArc/hypofractionation regimen or 3D conformal/conventional fractionation) for localized PC. Total white blood cell (WBC), absolute lymphocyte counts (ALCs), and peripheral immune cell subpopulations were analyzed at baseline, at the end of RT, and 3 and 6 months after the end of RT. WBC and ALC greatly decreased at the end of RT with a trend to recover at 6 months' follow-up in the hypofractionation group but not in the conventional one. Furthermore, B, total T, T CD4+, T CD8+, and NK cell values dropped significantly in both groups at the end of RT, with a minor decrease detectable in the hypofractionation group for B, total T, and T CD4+ lymphocytes with respect to the other technique/fractionation group. Double-negative T (DNT), double-positive T (DPT), and NKT cells significantly decreased at the end of RT with a slight tendency to recover values during follow-up, particularly in the hypofractionation group. No correlation with genitourinary or gastrointestinal toxicity was found. In this study, we showed, for the first time, the effects of RapidArc/moderate hypofractionation RT on immune cell subsets in patients treated for localized PC. Due to the growing interest in minority T-cell subpopulations for immunotherapy, we also reported longitudinal monitoring of the effects of RT on DNT, DPT, and NKT, which was never studied before. Our preliminary data highlight the importance of considering the effects of different RT techniques/fractionation regimens on peripheral immune cells, in the era of RT and immunotherapy combination. [ABSTRACT FROM AUTHOR]

We report a patient with chronic lymphocytic leukemia (CLL) in whom a leukemic involvement of prostate and penis occurred in the advanced phase of his disease. Obstructive urinary symptoms were indicative of prostatic CLL infiltration, followed by the occurrence of an ulcerative lesion on the glans. Histologic examination confirmed the neoplastic B-cell infiltration. Both localizations responded to conventional treatments. A review of the literature confirms that leukemic involvement of the genito-urinary system is uncommon in CLL patients. However, it should be considered in CLL patients with urologic symptoms and a long history of the disease. [ABSTRACT FROM AUTHOR]

• 795 pts treated with early salvage RT for prostate cancer were investigated. • Median follow-up was 8.5 years; PSA = 0.43 ng/ml,EQD2: 71.3 Gy. 331 pts received PNI. • Biochemical failure data were fitted with a radiobiology based formula on the training cohort. • Fit was successful and prediction performances were confirmed in the validation cohort. • The model can individually assess failure risk based on Dose, PSA, ISUP grouping and PNI. Explainable models of long-term risk of biochemical failure (BF) after post-prostatectomy salvage radiotherapy (SRT) are lacking. A previously introduced radiobiology-based formula was adapted to incorporate the impact of pelvic nodes irradiation (PNI). The risk of post-SRT BF may be expressed by a Poisson-based equation including pre-SRT PSA, the radiosensitivity α, the clonogen density C, the prescribed dose (in terms of EQD2, α/β = 1.5 Gy) and a factor (1-BxλxPSA) accounting for clonogens outside the irradiated volume, being λ the recovery due to PNI. Data of 795 pT2-pT3, pN0/pN1/pNx (n = 627/94/74) patients with follow-up ≥ 5 years and pre-RT PSA ≤ 2 ng/mL were randomly split into training (n = 528) and validation (n = 267) cohorts; the training cohort data were fitted by the least square method. Separate fits were performed for different risk groups. Model performances were assessed by calibration plots and tested in the validation group. The median follow-up was 8.5y, median pre-SRT PSA and EQD2 were 0.43 ng/mL and 71.3 Gy respectively; 331/795 pts received PNI. The most clinically significant prognostic grouping was pT3b and/or ISUP4-5 versus pT2/3a and ISUP1-3. Best-fit parameters were α eff = 0.26/0.23 Gy−1, C = 107/107, B = 0.40/0.97, λ = 0.87/0.41 for low/high-risk group. Performances were confirmed in the validation group (slope = 0.89,R2 = 0.85). Results suggested optimal SRT dose at 70–74 Gy. The estimated reduction of post-SRT BF due to PNI at these dose values was > 5 % for PSA > 1/>0.15 ng/mL for low/high-risk patients, being > 10 % for high-risk patients with pre-SRT PSA > 0.25 ng/mL. An explainable one-size-fits-all equation satisfactorily predicts long-term risk of post-SRT BF. The model was independently validated. A calculator tool was made available. [ABSTRACT FROM AUTHOR]

• The overall worsening at two years of intestinal function in men treated with radiotherapy including pelvic node irradiation (PNI) for prostate cancer is generally mild. • Nevertheless, such worsening may be greater in a non-negligible fraction of patients, especially for specific symptoms such as frequency, gas passage, rectal bleeding and accidental soiling. • Men experiencing severe acute bowel symptoms from PNI are at higher risk of symptom persistence two years after irradiation. • This risk is only minimally dependent on baseline bowel symptoms, and not related to radiotherapy intent. 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. 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 Δ Acute (the worst decline between baseline and RT mid-point/end) was investigated. 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 Δ Acute largely modulated 2-year worsening: patients with Δ Acute greater than the first quartile (Q1) and Δ Acute 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 Δ Acute ≤ Q1 vs Δ Acute > Q1 group (p < 0.0001). 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. [ABSTRACT FROM AUTHOR]