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Abstract Background To analyse limits and capabilities in dose calculation of collapsed-cone-convolution (CCC) algorithm implemented in helical tomotherapy (HT) treatment planning system for thorax lesions. Methods The agreement between measured and calculated dose was verified both in homogeneous (Cheese Phantom) and in a custom-made inhomogeneous phantom. The inhomogeneous phantom was employed to mimic a patient's thorax region with lung density encountered in extreme cases and acrylic inserts of various dimensions and positions inside the lung cavity. For both phantoms, different lung treatment plans (single or multiple metastases and targets in the mediastinum) using HT technique were simulated and verified. Point and planar dose measurements, both with radiographic extended-dose-range (EDR2) and radiochromic external-beam-therapy (EBT2) films, were performed. Absolute point dose measurements, dose profile comparisons and quantitative analysis of gamma function distributions were analyzed. Results An excellent agreement between measured and calculated dose distributions was found in homogeneous media, both for point and planar dose measurements. Absolute dose deviations Conclusions Very acceptable accuracy was found for complex lung treatment plans calculated with CCC algorithm implemented in the tomotherapy TPS even in the heterogeneous phantom with very low lung-density.

Featured Application: The paper aim to propose an image-based parameter for response prediction in cervical cancer. Background: Recent studies have highlighted the potentialities of a radiobiological parameter, the early regression index (ERITCP), in the treatment response prediction for rectal cancer patients treated with chemoradiotherapy followed by surgery. The aim of this study is to evaluate the performance of this parameter in predicting pathological complete response (pCR) in the context of low field MR guided radiotherapy (MRgRT) for cervical cancer (CC). Methods: A total of 16 patients affected by CC were enrolled. All patients underwent a MRgRT treatment, with prescription of 50.6 Gy in 22 fractions. A daily MR acquisition was performed at simulation and on each treatment fraction. Gross tumor volume (GTV) was delineated on the MR images acquired at the following biological effective dose (BED) levels: 14, 28, 42, 54 and 62 Gy. The ERITCP was calculated at the different BED levels and its predictive performance was quantified in terms of receiver operating characteristic (ROC) curve. Results: pCR was observed in 11/16 cases. The highest discriminative power of ERITCP was reported when a BED value of 28 Gy is reached, obtaining an area under curve (AUC) of 0.84. Conclusion: This study confirmed ERITCP as a promising response biomarker also for CC, although further studies with larger cohort of patients are recommended. [ABSTRACT FROM AUTHOR]

Aim: Stereotactic ablative body radiation (SABRT) for lung cancer is a validated treatment’s option for early stage and advanced or oligoprogression disease. Therapeutic strategy in lung cancer for eldery patients is limited by their comorbidities or perfomance status. This is a retrospective analysis to evaluate the safety and efficiency of SBRT for the treatment of lung lesions in elderly patients. Material and methods: Between April 2018 and January 2021, 44 patients (pts) with more than seventy years old affected by lung cancer in early stage or advanced disease (lung metastasis) were treated with SABRT. Only one or two lesions were irradiated in each patients (total lesions: 60) Median age was 83,5 years (range 70-91). Patients were stratified by stage: stage IV (19), stage I (18), local relapse of previous surgery (7). Lesions’ histology distribution was: adenocarcinoma (26), squamous cell carcinoma (7), small cell lung cancer (5) and unknown (22) - biopsy not possible for medical condition. Lesions were treated with four different fractioned regimens depending on location: 50 Gy /5 fr (19), 45 Gy/ 3 fr (23), 54 Gy/3 fr (8) and 60 Gy/ 8 fr (10), prescribed to 80% median isodose curve (71,8-83%). Local control (LC) was defined by RECIST criteria, overall survival (OS) and toxicity according to CTCAE (v.4) were collected and analyzed retrospectively. Results: Median follow-up was 10 months (2,2-38,2 months). Local control (LC) rate was 85,3% and 74% at 12 and 24 months respectively. Twelve and 24 months - OS was 67,2% and 57,1% respectively. Dividing patients by stage, in stage I 12 and 24 months OS was 64,9% and 32,5%, while in stage IV 57% and 48,9%, with a difference not statistically significantly (p-value: 0,17). Significant lung toxicity wasn’t registered. Only two patients had G1 side effects: one, asthenia and the other thoracic wall pain. Conclusion: Based on our experience, SABR for eldery patients affected by lung cancer is efficient, well tolerated with a good patient’s compliance. In our opinion should be a valid option for the therapeutic strategy for this setting of patients. Further patients need to be treated in order to obtain a confirmation of this promising preliminary result. [ABSTRACT FROM AUTHOR]

Objective: To evaluate toxicity and outcomes after salvage robotic stereotactic body radiotherapy-SBRT- (CyberKnife®,Accuray, Sunnyvale, Ca) re-irradiation of patients with intraprostatic/prostatic bed recurrences of pelvic malignancies. Methods: From 11/2018 to 10/2021, 20 patients with intraprostatic/prostatic bed recurrence after radiotherapy, diagnosed on MRI/ PET choline/PSMA and/or biopsyproven, underwent a salvage re-irradiation with SBRT: 9 patients with prostate cancer failure after previous radical radiotherapy, and 11 patients after adjuvant/salvage radiotherapy. Median prior RT dose was 70.7 (38.25- 78) Gy and the median interval to SBRT salvage therapy was 79.3 (11-208) months. Median PSA before robotic SBRT was 2.64 (1.14-26.8) ng/ml. Fiducial markers were implanted into the target in 19 of 20 patients. Median SBRT total dose was 35 (30-35) Gy in 5 fractions (EQD2=85 Gy, for α/β 1.5). Median prescription isodose was 70% (59- 81%). In 12 patients, a “urethral sparing” was used. In 10 cases a precautionary therapy with steroids and alphalytics was prescribed during the salvage treatment. Twelve patients received neoadjuvant or concomitant/adjuvant androgen suppressive therapy during their SBRT course. Toxicity was scored in accordance with CTCAE v 5.0. Results: Median follow-up was 17.4 months (2.35- 38.15) months. Acute genitourinary (GU) toxicity was observed in 40% of patients and was limited to grade (G)1 in 35% of patients and G2 (minimal strangury, urgency and occasional urinary incontinence) in 5%. Ten% of patients reported late GU G3 toxicity (urinary retention requiring catheterization and transurethral resection), and 5% G2 urinary toxicity. No acute and late gastrointestinal toxicity was observed. At the last follow-up 2 patients died due to a non cancer-releated cause. Twenty-four-months Kaplan Meier estimates of biochemical relapse-free survival (bRFS) was 78.2% (see Figure 1), local-relapse-free survival (LRFS) 92.3% and distant-metastases-free survival 85.1%. Conclusions: Prostate SBRT re-irradiation with CK is a feasible treatment option, with good short-term outcomes. Longer follow-up is necessary to assess the long-term benefits and to determine late toxicity. [ABSTRACT FROM AUTHOR]

Objective: We analyzed initial outcomes and toxicities of the 2 schedules of stereotactic body radiotherapy (SBRT) in use in our department for prostate cancer (PCa) patients. Materials and methods: Between 10/2017-05/2021, 102 PCa patients were treated using robotic SBRT with two different schedules. Group I included 73 patients treated at 36.25 Gy/ 5 fractions at the 79% median isodose, group II 29 patients treated at 38 Gy/ 4 fractions at the 63% median isodose (urethral sparing HDR-like technique). Median age was 74.5 vs 75.8 years, median initial PSA 7.20 vs 7.65 ng/ml. Gleason score was 3+3 in 11% vs 17.2%, 3+4 in 58.9% vs 51.7%, 4+3 in 17.8% vs 20.7% and not accorded (due to previous androgen deprivation) in 1.4% vs 3.5% of patients. Androgen deprivation therapy (ADT) was prescribed in 45% vs 31% of patients, with a median duration of 7 vs 6 months. Fiducial markers were implanted into the prostate in all patients. In 52% of patients steroid therapy and/or alpha-lytics were prescribed to prevent side effects. Toxicity was scored in accordance with CTCAE v 5.0. Biochemical failure was assessed using the nadir + 2 definition. Results: Median follow-up was 23.4 (0-47.2) months in group I vs 12 (2.78-36.07) months in group II. For acute and late toxicities see Table 1. No acute grade(G) 3 toxicities were registered. One (1.4%) late G3 genitourinary toxicity (transurethral incision) occurred in a patient treated with 36.25 Gy. Median post-SBRT PSA level was 0.342 (0.001-231.00) ng/ml in group I and 0.603 (0.05-10.210) ng/ml in group II. At the last follow up 3 pts had died due to a non-cancer related cause, 4 pts had a biochemical failure with PSMA/CholinePET positive progression: 3 treated at 36.25 Gy and 1 treated at 38 Gy. Two-year biochemical relapse-free survival(bRFS) was 94.8% for the patients of group I and 88.9% for the patients of group II, respectively (p= 0.6). Overall survival (OS) was 85.7%vs 98.4% at 2 years(p=0.35). Disease-free survival(DFS) was 94.8% and 88.9%, respectively (p=0.6). No correlation was found between target volume and toxicity. Conclusion: The urethral sparing technique allowed dose escalation (from 2 Gy equivalent dose-EQD2-91 Gy to EQD2 ≥ 120 Gy with α/β 1.5) without increasing G3 toxicity and with non-inferior bRFS despite less ADT prescription. Longer follow-up is needed to confirm these results. [ABSTRACT FROM AUTHOR]

Purpose: The treatment of relapses of already irradiated primary brain tumors and metastases is difficult, given the limited effectiveness of systemic therapy and the risks of surgery or re-irradiation. Here we present the results of salvage Stereotactic Radiotherapy (SRT) for the treatment of recurrent primary brain tumors and metastases (mts) after previous radiotherapy (RT). Material/methods: From January 2018 to October 2021, 137 intracranial lesions (33 patients) were re-irradiated with robotic SRT. Primary histology was: NSCLC (n=10), breast cancer (n=9), glioblastoma (n=4), meningioma (n=2), oligodendroglioma (n=2), hemangiopericytoma (n=2), pituitary adenoma (n=2), prostate cancer (n=1), and melanoma (1). Previous RT on the same volume were performed with: GammaKnife (n=11), CyberKnife (n=8), Whole-Brain RT (n=8), post-operative IMRT/ Helical IMRT (n=8), VMAT-SRT (n=5), post-operative 3D-CRT (n=3). Eight patients had multiple previous treatments. Median time from the previous radiotherapy was 13 (3-377) months. Gross Tumor Volume (GTV) was delineated on computed tomography and contrast-enhanced T1 magnetic resonance. Median GTV was 5.24 (0.22-78.32) cc. Planning Target Volume (PTV) was obtained adding an expansion to GTV of 1 mm (for brain metastases), or 3 mm (for glioblastoma). Median PTV was 10.19 (0.43-136.9) cc. Median prescribed dose was 30 (24-37.5) Gy in 1-5 fractions (median number of fractions was 5), at a median isodose of 76% (67-80%). The patients were followed up with contrast-enhanced MRI performed every three months. Results: SRT was delivered on a median number of 2 (1-24) lesions; 7 patients were treated on ≥ 5 lesions simultaneously (from 5 to 24 lesions). Acute toxicity was G2 headache in three patients (GTV>1cc or >3 lesions), controlled by increasing the dose of steroids. Median follow-up after re-irradiation in 20 evaluable patients was 9 (1-37) months. Radionecrosis occurred in only one patient (GTV>1cc). He underwent two previous VMAT SRT (prescribed dose 30 Gy in 5 fractions and 21 Gy in 3 fractions) and presented seizures. He was treated with steroids and levetiracetam. Six-, 12-, 18-month overall survival (OS) was 79.2%, 51.7%, 37.7% respectively. Six-, 12-, 18-month local relapse free survival was 70.7%, 64.8%, 48.6% respectively (see Figure 1). Conclusions: SRT for re-irradiation is feasible, with only one case of radionecrosis registered. The treatment is effective with 12-month local control registered in 65% of pts. An accurate patient selection is warranted in order to avoid toxicity and a longer follow-up is needed to confirm the low radionecrosis rate. [ABSTRACT FROM AUTHOR]

Object: Lung metastases from colorectal cancer are more radioresistant, requiring higher dose to obtain a stable local control. Here we evaluate two different techniques of stereotactic body radiotherapy (SBRT) for lung metastases from colorectal cancer in patients treated in our departmed. Material and methods: From 01/2006 to 07/2020, 69 lung metastases (37 patients) from colorectal cancer were treated with SBRT in our department: 48 lesions (27 patients) with 4DCT simulation and helical/VMAT IGIMRT (4DCT) and 21 lesions (10 patients) with real time-tracking robotic radiosurgery (CK). Median ages were 71.9 years (4DCT) vs 64.1 years (CK). Median GTV were 5.16 (0.31-88.6) cc (4DCT) vs 3.98 (0.16-16) cc (CK), while median PTV were 26.3 (6.3-180) (4DCT) cc vs 16.7 (1.9 vs 45.6) cc (CK), respectively. The tighter margins used with the real-time tracking was the main factor that determined a smaller PTV volume. Central lesions were 17.1% in the 4DCT group vs 23.5% in the CK group. Median BED precribed was 102.6 Gy in the 4DCT group vs 112.5 Gy in the CK group. The tighter margins allowed us not only to prescribe a higher median BED, but also to reduce the number of fractions and the overall treatment time from 2 weeks with 6 fractions every other day to 3 consecutive daily fractions. Results: Median follow-ups were 26.4 (3-85.7) months (4DCT group) vs 16.4 (3.4-37.4) months (CK group). The treatment was well tollerated: one patient presented a grade (G) 3 pneumonitis after a treatment on 6 lesions/4 PTV’s in one month with CK. Fully recovered she died one year later for distant metastases. Five patients presented G1/G2 cough and 1 with G1 dyspnea soon after the 4DCT treatment. Four patients had persistent G1 fibrosis, and 7 G1 dyspnea after the 4DCT treatment. Local control was of 69.3% (4DCT) vs 90.5% (CK) at 12 months, 46.5% vs 81.4% at 24 months (p= 0.08) (see Fig. 1). Overall survival at 12 months was 89.5% in the CK group vs 94.7% in the 4DCT group, at 24 months 64.6 % vs 76.5 %, and at 36 months 64.6% vs 51.7%, respectively. Conclusion: SBRT in lung oligometastases from colorectal cancer have a low toxicity profile. Even a small increase of BED from 102 Gy to 112 Gy, and the higher precision allowed by the real-time tracking shows a tendency towards better local control. [ABSTRACT FROM AUTHOR]