10-yr Results of Moderately Hypofractionated Postoperative Radiotherapy for Prostate Cancer Focused on Treatment Related Toxicity.

INTRODUCTION: To retrospectively report long term outcomes following postoperative hypofractionated radiotherapy (RT) for prostate cancer, emphasizing treatment related toxicity. MATERIAL AND METHODS: Patients for whom adjuvant or salvage RT was indicated after prostatectomy were treated with a course of moderate hypofractionation consisting in the delivery of 62.5 Gy in 25 fractions (2.5 Gy per fraction) on the prostate bed in 5 consecutive weeks (EQD21.5 = 70 Gy) by means of 3D-CRT in most of them. Androgen deprivation therapy (ADT) was allowed at physician's discretion. Patients were evaluated for urinary and rectal complications according to the Common Terminology Criteria for Adverse Events v4 (CTCAE v.4). Overall survival (OS), biochemical recurrence free survival (bRFS), and metastasis-free survival (MFS) were estimated using the Kaplan-Meier method. RESULTS: One hundred and ten patients with a median age of 67 years (range 51-78) were enrolled. The majority of them (82%) had adverse pathologic features only, while 31 (28%) had early biochemical relapse. Median PSA level before RT was 0.12 ng/mL (range 0-9 ng/mL). Median time from surgery was 4 months (range 1-136 months). Twenty-eight patients (25.4%) also received ADT. At a median follow up of 103 months (range 19-138 months), late Grade 3 and Grade 4 rectal toxicity were 0.9% (1 case of hematochezia) and 0.9% (1 case of fistula), respectively, while late Grade 3 GU side effects (urethral stenosis) occurred in 9 cases (8%). No late Grade 4 events were observed, respectively. Ten-year OS, b-RFS and MFS were 77.3% (95%CI: 82.1%-72.5%), 53.3% (95%CI: 59.9%-47.6%), and 76.7% (95%CI: 81.2%-72.2%), respectively. CONCLUSION: Our study provides long term data that a shortened course of postoperative RT is as safe and effective as a long course of conventionally fractionated RT and would improve patients' convenience and significantly reduce RT department workloads.

Durable complete response to PET-CT driven stereotactic radiation therapy plus pembrolizumab for pleomorphic Pancoast cancer: Case report and literature review.

PET-driven SBRT plus pembrolizumab as first-line therapy against pleomorphic Pancoast cancer appears beneficial, probably due to high equivalent doses of SBRT on photopenic necrotic core and synergic immune system stimulation of immunoradiotherapy.

Factors influencing local control after MR-guided stereotactic body radiotherapy (MRgSBRT) for adrenal metastases.

Purpose: Stereotactic body radiotherapy (SBRT) is an effective treatment for adrenal gland metastases, but it is technically challenging and there are concerns about toxicity. We performed a multi-institutional pooled retrospective analysis to study clinical outcomes and toxicities after MR-guided SBRT (MRgSBRT) using for adrenal gland metastases. Methods and Materials: Clinical and dosimetric data of patients treated with MRgSBRT on a 0.35 T MR-Linac at 11 institutions between 2016 and 2022 were analyzed. Local control (LC), local progression-free survival (LPFS), distant progression-free survival (DPFS) and overall survival (OS) were estimated using Kaplan-Meier method and log-rank test. Results: A total of 255 patients (269 adrenal metastases) were included. Metastatic pattern was solitary in 25.9 % and oligometastatic in 58.0 % of patients. Median total dose was 45 Gy (range, 16-60 Gy) in a median of 5 fractions, and the median BED10 was 100 Gy (range, 37.5-132.0 Gy). Adaptation was done in 87.4 % of delivered fractions based on the individual clinicians' judgement. The 1- and 2- year LPFS rates were 94.0 % (95 % CI: 90.7-97.3 %) and 88.3 % (95 % CI: 82.4-94.2 %), respectively and only 2 patients (0.8 %) experienced grade 3 + toxicity. No local recurrences were observed after treatment to a total dose of BED10 > 100 Gy, with single fraction or fractional dose of > 10 Gy. Conclusions: This is a large retrospective multi-institutional study to evaluate the treatment outcomes and toxicities with MRgSBRT in over 250 patients, demonstrating the need for frequent adaptation in 87.4 % of delivered fractions to achieve a 1- year LPFS rate of 94 % and less than 1 % rate of grade 3 + toxicity. Outcomes analysis in 269 adrenal lesions revealed improved outcomes with delivery of a BED10 > 100 Gy, use of single fraction SBRT and with fraction doses > 10 Gy, providing benchmarks for future clinical trials.

Role of 18F-FCH PET/CT in Detecting Recurrences of Prostate Cancer After Curative Treatments.

Objectives: To evaluate the role of 18F-fluorocholine (18F-FCH) positron emission tomography/computed tomography (PET/CT) in prostate cancer (PC) patients with biochemical recurrence who were submitted to different curative treatments. Methods: Seventy-five patients with PC who underwent 18F-FCH PET/CT for biochemical recurrence were retrospectively analyzed to distinguish patients who were submitted only to prostatectomy (PR group), only to radiotherapy (RT) on prostate with curative intent (RT group), and to both (PR + RT group). Correlations between 18F-FCH PET/CT and outcome and between prostate-specific antigen (PSA) values and sites and the number of metastases were analyzed. The performance of 18F-FCH PET/CT in relation to the PSA value and of maximum standardized uptake value (SUVmax) value in relation to patient outcome were assessed by receiver operating characteristic (ROC) curves. Results: 18F-FCH PET/CT relapses mostly involved lymph nodes, bones, and prostate bed. K-cohen test showed moderate agreement with the outcome in the whole population and in the PR group, whereas in the RT group it was perfect and in PR + RT fair. A statistically significant difference in PSA values was observed in the presence of lymph node metastases and with multiple metastases. ROC curves showed PSA cut-off values of 1.96 ng/dL, 1.95, 1.81, and 2.96, respectively, in the whole population, PR, RT and PR + RT group. SUVmax cut-off values of 3.75, 3.45, and 4.7 were described in the whole population, PR group, and PR + RT group. Conclusion: The study confirms that 18F-FCH PET/CT is still valid in PC patients with suspected biochemical recurrence. Therefore, we can affirm that it still makes sense to perform it both with high PSA values and with lower values when prostate-specific membrane antigen tracers are not available.

Stereotactic MR-guided adaptive radiotherapy (SMART) for primary rectal cancer: evaluation of early toxicity and pathological response.

Background: The purpose of this study is to measure the effects of stereotactic MR-guided adaptive radiotherapy (SMART) for rectal cancer patients in terms of early toxicity and pathological response. Materials and methods: For this prospective pilot study, patients diagnosed with locally advanced rectal cancer (LARC) with positive lymph node clinical staging underwent SMART on rectal lesion and mesorectum using hybrid MR-Linac (MRIdian ViewRay). Dose prescription at 80% isodose for the rectal lesion and mesorectum was 40 Gy (8 Gy/fr) and 25 Gy (5 Gy/fr), respectively, delivered on 5 days (3 fr/week). Response assessment by MRI was performed 3 weeks after SMART, then patients fit for surgery underwent total mesorectal excision. Primary endpoint was evaluation of adverse effect of radiotherapy. Secondary endpoint was pathological complete response rate. Early toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Results: From October 2020 to January 2022, twenty patients underwent rectal SMART. No grade 3-5 toxicity was recorded. Twelve patients were eligible for total mesorectal excision (TME). Mean interval between the completion of SMART and surgery was 4 weeks. Pathological downstaging occurred in all patients; rate of pathological complete response (pCR) was 17%. pCR occurred with a prolonged time to surgery (> 7 weeks). Conclusion: To our knowledge, this is the first study to use stereotactic radiotherapy for primary rectal cancer. SMART for rectal cancer is well tolerated and effective in terms of tumor regression, especially if followed by delayed surgery.

Magnetic resonance guided SBRT reirradiation in locally recurrent prostate cancer: a multicentric retrospective analysis.

AIMS: Reirradiation of prostate cancer (PC) local recurrences represents an emerging challenge for current radiotherapy. In this context, stereotactic body radiation therapy (SBRT) allows the delivery of high doses, with curative intent. Magnetic Resonance guided Radiation Therapy (MRgRT) has shown promising results in terms of safety, feasibility and efficacy of delivering SBRT thanks to the enhanced soft tissue contrast and the online adaptive workflow. This multicentric retrospective analysis evaluates the feasibility and efficacy of PC reirradiation, using a 0.35 T hybrid MR delivery unit. METHODS: Patients affected by local recurrences of PC and treated in five institutions between 2019 and 2022 were retrospectively collected. All patients had undergone previous Radiation Therapy (RT) in definitive or adjuvant setting. Re-treatment MRgSBRT was delivered with a total dose ranging from 25 to 40 Gy in 5 fractions. Toxicity according to CTCAE v 5.0 and treatment response were assessed at the end of the treatment and at follow-up. RESULTS: Eighteen patients were included in this analysis. All patients had previously undergone external beam radiation therapy (EBRT) up to a total dose of 59.36 to 80 Gy. Median cumulative biologically effective dose (BED) of SBRT re-treatment was 213,3 Gy (103,1-560), considering an α/ß of 1.5. Complete response was achieved in 4 patients (22.2%). No grade ≥ 2 acute genitourinary (GU) toxicity events were recorded, while gastrointestinal (GI) acute toxicity events occurred in 4 patients (22.2%). CONCLUSION: The low rates of acute toxicity of this experience encourages considering MRgSBRT a feasibile therapeutic approach for the treatment of clinically relapsed PC. Accurate gating of target volumes, the online adaptive planning workflow and the high definition of MRI treatment images allow delivering high doses to the PTV while efficiently sparing organs at risk (OARs).

Economic Evaluations of Magnetic Resonance Image-Guided Radiotherapy (MRIgRT): A Systematic Review.

OBJECTIVES: This review systematically summarizes the evidence on the economic impact of magnetic resonance image-guided RT (MRIgRT). METHODS: We systematically searched INAHTA, MEDLINE, and Scopus up to March 2022 to retrieve health economic studies. Relevant data were extracted on study type, model inputs, modeling methods and economic results. RESULTS: Five studies were included. Two studies performed a full economic assessment to compare the cost-effectiveness of MRIgRT with other forms of image-guided radiation therapy. One study performed a cost minimization analysis and two studies performed an activity-based costing, all comparing MRIgRT with X-ray computed tomography image-guided radiation therapy (CTIgRT). Prostate cancer was the target condition in four studies and hepatocellular carcinoma in one. Considering the studies with a full economic assessment, MR-guided stereotactic body radiation therapy was found to be cost effective with respect to CTIgRT or conventional or moderate hypofractionated RT, even with a low reduction in toxicity. Conversely, a greater reduction in toxicity is required to compete with extreme hypofractionated RT without MR guidance. CONCLUSIONS: This review highlights the great potential of MRIgRT but also the need for further evidence, especially for late toxicity, whose reduction is expected to be the real added value of this technology.

The predictive value of 18F-FDG PET-CT for assessing the clinical outcomes in locally advanced NSCLC patients after a new induction treatment: low-dose fractionated radiotherapy with concurrent chemotherapy.

BACKGROUND: Patients with locally advanced non-small-cell lung cancer (LA-NSCLC) have poor prognosis despite several multimodal approaches. Recently, low-dose fractionated radiotherapy concurrent to the induction chemotherapy (IC-LDRT) has been proposed to further improve the effects of chemotherapy and prognosis. Until now, the predictive value of metabolic response after IC-LDRT has not yet been investigated. AIM: to evaluate whether the early metabolic response, assessed by 18F-fluoro-deoxyglucose positron emission-computed tomography (18F-FDG PET-CT), could predict the prognosis in LA-NSCLC patients treated with a multimodal approach, including IC-LDRT. METHODS: Forty-four consecutive patients (35males, mean age: 66 ± 7.8 years) with stage IIIA/IIIB NSCLC were retrospectively evaluated. Forty-four patients underwent IC-LDRT (2 cycles of chemotherapy, 40 cGy twice daily), 26/44 neo-adjuvant chemo-radiotherapy (CCRT: 50.4Gy), and 20/44 surgery. 18F-FDG PET-CT was performed before (baseline), after IC-LDRT (early) and after CCRT (final), applying PET response criteria in solid tumours (PERCIST). Patients with complete/partial metabolic response were classified as responders; patients with stable/progressive disease as non-responders. Progression free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meyer analysis; the relationship between clinical factors and survivals were assessed using uni-multivariate regression analysis. RESULTS: Forty-four out of 44, 42/44 and 23/42 patients underwent baseline, early and final PET-CT, respectively. SULpeak of primary tumour and lymph-node significantly (p = 0.004, p = 0.0002, respectively) decreased after IC-LDRT with a further reduction after CCRT (p = 0.0006, p = 0.02, respectively). At early PET-CT, 20/42 (47.6%) patients were classified as responders, 22/42 (52.3%) as non-responders. At final PET-CT, 19/23 patients were classified as responders (12 responders and 7 non-responders at early PET-CT), and 4/23 as non-responders (all non-responders at early PET-CT). Early responders had better PFS and OS than early non-responders (p ≤ 0.01). Early metabolic response was predictive factor for loco-regional, distant and global PFS (p = 0.02, p = 0.01, p = 0.005, respectively); surgery for loco-regional and global PFS (p = 0.03, p = 0.009, respectively). CONCLUSIONS: In LA-NSCLC patients, 18F-FDG metabolic response assessed after only two cycles of IC-LDRT predicts the prognosis. The early evaluation of metabolic changes could allow to personalize therapy. This multimodality approach, including both low-dose radiotherapy that increases the effects of induction chemotherapy, and surgery that removes the disease, improved clinical outcomes. Further prospective investigation of this new induction approach is warranted.