Evaluation of Efficacy and Tolerance of Radical Radiotherapy and Radiochemotherapy in Treatment of Locally Advanced, Unresectable Rectal Cancer.

Background: A retrospective evaluation of tolerance and efficacy of two schemes of neoadjuvant treatment in patients (pts) with unresectable rectal cancer: radiochemotherapy (CRT) and radiotherapy (RT), including conventional and accelerated hyperfractionation. Material and Method: A total of 145 consecutive pts with unresectable, locally advanced rectal cancer. The schemes used are RT in 73 (50%) or CRT in 72 (50%). In CRT, 54 Gy in 1.8 Gy fractions was given with chemotherapy, In the RT group, conventional fractionation (CFRT) and hyperfractionated accelerated radiotherapy (HART). HART was introduced at first as an alternative to CFRT, after radiobiological studies suggesting a therapeutic gain of hyperfractionation in other cancers, and second to administer relatively high dose needed in unresectable cancer, which is not feasible in hypofractionation because of critical organs sensitivity to high fraction doses (fd). HART was an alternative option in pts with medical contraindications to chemotherapy and to shorten overall treatment time with greater radiobiological effectiveness than CFRT. Results: Objective response (OR) in the RT and CRT group was 60% versus 75%. Resection rate (RR) in RT and CRT: 37% versus 65%. Tumor mobility and laparotomy-based unresectability were significant factors for OR. Performance status (PS), tumor mobility, and neoadjuvant treatment method were significant for RR.

Systemic modulation of stress and immune parameters in patients treated for prostate adenocarcinoma by intensity-modulated radiation therapy or stereotactic ablative body radiotherapy.

BACKGROUND: In this exploratory study, the impact of local irradiation on systemic changes in stress and immune parameters was investigated in eight patients treated with intensity-modulated radiation therapy (IMRT) or stereotactic ablative body radiotherapy (SABR) for prostate adenocarcinoma to gain deeper insights into how radiotherapy (RT) modulates the immune system. PATIENTS AND METHODS: RT-qPCR, flow cytometry, metabolomics, and antibody arrays were used to monitor a panel of stress- and immune-related parameters before RT, after the first fraction (SABR) or the first week of treatment (IMRT), after the last fraction, and 3 weeks later in the blood of IMRT (N = 4) or SABR (N = 4) patients. Effect size analysis was used for comparison of results at different timepoints. RESULTS: Several parameters were found to be differentially modulated in IMRT and SABR patients: the expression of TGFB1, IL1B, and CCL3 genes; the expression of HLA-DR on circulating monocytes; the abundance and ratio of phosphatidylcholine and lysophosphatidylcholine metabolites in plasma. More immune modulators in plasma were modulated during IMRT than SABR, with only two common proteins, namely GDF-15 and Tim­3. CONCLUSION: Locally delivered RT induces systemic modulation of the immune system in prostate adenocarcinoma patients. IMRT and SABR appear to specifically affect distinct immune components.

CyberKnife stereotactic radiosurgery and stereotactic ablative radiation therapy of patients with prostate cancer bone metastases.

The aim of the study was to evaluate the effectiveness and toxicity of CyberKnife (CK) stereotactic radiosurgery (SRS) and stereotactic ablative radiation therapy (SABR) of patients with prostate cancer bone metastases. Analysis of prognostic and predictive factors was also performed. Material consisted of 51 patients with 71 bone oligometastases treated using CK SRS/SABR. In half of the patients single lesion was treated, in half 2-5 lesions. Median PSA concentration at the time of metastasis detection was 5.75 ng/ml. Total dose of 6-45Gy (median 20) was delivered with 1-5 fractions of 6-15 Gy (median 9). Biologic equivalent dose (BED) (α/ß=1.6) over 100 Gy was delivered to 45 lesions (63%) in 38 patients (75%). In statistical analysis Kaplan-Meier method, log-rank test and the Cox proportional hazard model were used. One-, two- and three-year overall survival (OS) was 90%, 76% and 70%, respectively. All patients having PSA concentration lower that 1 ng/ml at last control lived at least three years. One-, two- and three- year local control (LC) was 97%, 70% and 30%. Patients with PSA below 20 ng/ml at the time of metastasis detection had better local control of lesions and lower PSA at the last control. Median of PSA concentration after CK based SRS/SABR remains stable during first 12 months of follow-up, dropped during the next months and at last control was comparable to initial level. Median PSA at last control in patients without disease progression was 1.67ng/ml and 20 patients had PSA below 1.0ng/ml. At the last control 59% of patients had no other metastases. Rapid pain decrease was observed in analysed group and during each control about 90% of patients had pain relief. No major toxicity was observed, 3 patients suffered from fracture of irradiated bone.SRS/SABR of prostate cancer bone oligometastases provides good LC of lesions, excellent pain control without additional toxicity. Patients with PSA concentration below 20ng/ml at the time of metastasis detection have better LC and PSA concentration response.