Defining a parameter to select the best radiotherapy technique in patients with right breast cancer after conservative surgery: Evaluation of high doses and risk of radio-induced second tumors to the ipsilateral lung.

PURPOSE: In the adjuvant right breast radiation therapy, after breast-conserving surgery, we wanted to look for a parameter that would help in the choice between the 3D-CRT or VMAT techniques, considering the risk of pneumonia to the ipsilateral lung (IL) linked to high doses. We also investigated the risk of second tumors in the IL related to the VMAT low doses. METHODS: We examined twenty-five 3D-CRT and thirty-five VMAT technique plans, between September 2022 and September 2023. We collected the MAximum Thickness of Ipsilateal Lung (MATIL) included between lateral and medial target borders for evaluating the risk of pneumonia due to the high dose (V20Gy), finally we calculated the Excess of Absolute Risk related to the second tumor risk due to the low dose. RESULTS: VMAT technique showed a better dose conformity than 3D-CRT. We detected a linear relationship between the V20Gy and MATIL of the IL only for the 3D-CRT technique; over a threshold value of MATIL the 3D-CRT is disadvantaged compared to the VMAT in terms of the risk of toxicity to the IL. We calculated that for every Gy more in average dose, a 12 % increase in the risk of induced cancer is expected. CONCLUSIONS: In the adjuvant right breast RT, the MATIL is a good surrogate parameter to predict the need to use a VMAT technique to limit high doses to IL. VMAT technique, according to the IL second tumor estimated risk, seems justified.

CBCT-based Prostate IGRT With and Without Implanted Markers: Assessment of Geometric Corrections and Time for Completion.

BACKGROUND/AIM: Cone-beam computed tomography (CBCT) is the most commonly used system in modern radiotherapy of prostate cancer for daily positioning verification. The use of intraprostatic radiopaque fiducials (FMs) may be added to CBCT. We wanted to investigate the possible advantage of using FMs in daily CBCT repositioning. MATERIALS AND METHODS: We selected three CBCTs for each treatment course for 13 patients (seven with and six without use of FMs) treated at our centre. Seven experienced Radiation Oncologists retrospectively reviewed the CBCTs, recording couch movements for correct patient positioning, and time spent to do it. Analysis of variance and t-test were carried out for comparison of different groups and for differences in mean values of the movements recorded (with p<0.05 as significance level). RESULTS: No statistically significant difference was found between operators in the analysis of images with FMs nor of images without them. A difference was only found in the mean corrections in couch rotation and pitch angle, which were higher in the FM group, and in the mean time for image analysis, which was shorter in this group. Using the van Herk formula, we found a possible reduction of clinical target volume and planning target volume margins for the FM group. CONCLUSION: According to our study, the use of intraprostatic FMs in daily CBCT seems useful for better detection of and correction for non-negligible rotational errors. Furthermore, FMs reduced the time to treatment start, which is very important in reducing the risk of intrafraction organ motion. These results need to be confirmed by further studies.

Is the alpha-beta ratio of prostate cancer really low? A prospective, non-randomized trial comparing standard and hyperfractionated conformal radiation therapy.

BACKGROUND AND PURPOSE: The objectives of the current study were to compare genito-urinary (GU) and gastro-intestinal (GI) toxicities as well as biochemical control (bRFS) in prostate cancer, utilizing conventional (2.0 Gy daily) (STD) or hyperfractionated (HFX) conformal irradiation (CRT). HFX (1.2 Gy BID) was chosen as a radiobiological method to try to reduce long term sequelae without compromising local control. PATIENTS AND METHODS: Three-hundred-and-seventy consecutive patients (pts) entered this prospective, non-randomized trial in the period January 1993-January 2003; 209 were treated with STD and 161 with HFX CRT. All were evaluable for acute toxicity analysis, 179 (STD) and 151 pts (HFX) being evaluable for late sequelae and bRFS analyses. Pt characteristics were not statistically different in the two groups. CRT consisted of a 4-field technique for prostate and/or pelvic nodes and a 5-field boost with rectal shielding. Median doses were 74 and 79.2 Gy for STD and HFX patients respectively, the latter dose being isoeffective for tumour control assuming alpha/beta=10 (EQD(2)=73.9 Gy). Median follow-up was 29.4 months (25.2 mos for STD; 37.7 mos for HFX; P<0.01). The two regimens were compared in terms of acute and late GU and GI toxicities and 5-year bRFS by univariate and multivariate analyses. RESULTS: Acute grade> or =2 GU toxicity was higher in the STD group (48.6% versus 37.3% in HFX, P=0.03), while no significant difference was found for acute GI toxicity. Late grade> or =2 GU and GI toxicities were lower in the HFX group (5-year actuarial rate: GU: 10.1% versus 20.3%, P=0.05; GI: 6.0% versus 10.6%, P=0.18). Five-year bRFS were 70% (+/-13.8%, 95% CI) and 82.6% (+/-7.2%) for STD and HFX, respectively (P=0.44); a trend favouring HFX was found in the subgroup of pts who did not receive hormonal therapy (5-year bRFS: 85.9%+/-12.4% versus 63.9%+/-23.8%, P=0.15). Multivariate analysis revealed only risk groups and age statistically related to bRFS but not fractionation regimen. Using the Nahum-Chapman TLCP model and prostate parameter set, which includes hypoxia, the TLCPs are approximately equal for the two regimens, whereas assuming alpha/beta=1.5 and no hypoxia we obtain 73% for the STD group but only 36% for the HFX group. CONCLUSIONS: As expected from radiobiological considerations, HFX reduces GI and GU late toxicities. Concerning early bRFS, our clinical findings suggest that HFX is no less effective than STD when delivering an isoeffective (alpha/beta=10) dose. Despite the relatively short follow-up, this result appears to be inconsistent with a low alpha/beta ratio for prostate cancer.

Long-term biochemical control of prostate cancer after standard or hyper-fractionation: evidence for different outcomes between low-intermediate and high risk patients.

BACKGROUND AND PURPOSE: To report the long-term biochemical control of a non-randomized trial comparing standard (STD) and hyper-fractionated (HFX) radiation schedules for prostate cancer treatment. MATERIALS AND METHODS: Between 1993 and 2003, 370 patients entered the study; 330/370 (STD: 179; HFX: 151) were evaluable for current analysis. Median doses were 79.2 Gy and 74 Gy for HFX (1.2 Gy/fr, two daily fractions) and STD (2 Gy/fr), respectively; median follow-up was 7.5 yr. The two regimens were compared in terms of biochemical relapse-free survival (according to ASTRO definition, bRFS) by univariate (log-rank test) and multivariate analyses (Cox regression hazard model). Based on published relationships between EQD2 and 5-yr biochemical control, α/ß values for each subgroup could be estimated. RESULTS: 7.5 yr bRFS were 53.4% (± 4.4%, 95% CI) and 65.4% (± 4.0%) for HFX and STD, respectively (p=0.13); HFX was associated with a poorer outcome in NCCN low+intermediate patients (7.5 yr bRFS: 56.6% vs 73.5%, p=0.048) while no differences were seen for high-risk patients (7.5 yr bRFS: 44.1% vs 45.3%). Multivariate analysis revealed that NCCN risk grouping (high vs low+intermediate; OR: 0.59, p=0.009) and age (< vs ≥ 70 yr; OR: 0.67, p=0.03) were the main predictors of worse bRFS. In the subgroups of low+intermediate-risk patients < 70 yr, the poorer outcome of HFX was more evident (7.5 yr bRFS: 47.1% vs 70.9%, p=0.078) while no difference was seen for older patients (7.5 yr bRFS: 69.4% vs 72.0%, p=0.76). Our α/ß estimates differ between low+intermediate-risk and high-risk patients. CONCLUSIONS: The bRFS long-term results of this non-randomized trial are consistent with different sensitivities to fractionation depending on NCCN risk grouping. The impact of age on the outcome of HFX for younger low+intermediate patients is consistent with an incomplete repair effect in older patients.