A "SHort course Accelerated RadiatiON therapy" (SHARON) During and Beyond the COVID-19 Pandemic

The current pandemic situation posed significant problems for radiotherapy (RT) services. In addition to the need to treat COVID-positive patients, it is important to protect health workers and healthy patients from the infection. Although some restrictions are being removed, it is not sure when the pandemic is actually going to be definitively over. Radiation oncologists (ROs) will be forced to face the pandemic for an unknown time interval (1). A recent guideline has been published on the possibility of adapting RT strategies in all settings (2). Particularly along the first months of pandemic spread, hypofractionated RT schedules adequately managing different clinical settings have been proposed to reduce the number of interactions and contacts in hospitals (for both patients–patients and patients–RT personnel), while delivering effective treatments (3–5). Only few were specifically dedicated to palliative RT or particularly oriented to relevant palliative presentations (e.g., bone metastases) (6). With the aim of decreasing hospital contacts, it has been proposed to omit, or delay, or modify the usual prescribed RT regimens (6), more often for palliative settings. However, in the field of palliative RT any omission and delay can dramatically worsen patients’ quality of life. In fact, the proposal to omit palliative radiotherapy during the COVID-19 pandemic has not been widely accepted, with some authors being worried by its clinical and ethical implications (7, 8). We would like to draw attention to a RT regimen tested in different settings. This scheme of SHort course Accelerated RadiatiON therapy: “SHARON” allows to complete a palliative RT course in four sessions and in only 2 days, using a double daily fractionation

Intensity modulated radiation therapy for breast cancer: Current perspectives

open9noBackground: Owing to highly conformed dose distribution, intensity modulated radiation therapy (IMRT) has the potential to improve treatment results of radiotherapy (RT). Postoperative RT is a standard adjuvant treatment in conservative treatment of breast cancer (BC). The aim of this review is to analyze available evidence from randomized controlled trials (RCTs) on IMRT in BC, particularly in terms of reduction of side effects. Methods: A literature search of the bibliographic database PubMed, from January 1990 through November 2016, was performed. Only RCTs published in English were included. Results: Ten articles reporting data from 5 RCTs fulfilled the selection criteria and were included in our review. Three out of 5 studies enrolled only selected patients in terms of increased risk of toxicity. Three studies compared IMRT with standard tangential RT. One study compared the results of IMRT in the supine versus the prone position, and one study compared standard treatment with accelerated partial breast IMRT. Three studies reported reduced acute and/or late toxicity using IMRT compared with standard RT. No study reported improved quality of life. Conclusion: IMRT seems able to reduce toxicity in selected patients treated with postoperative RT for BC. Further analyses are needed to better define patients who are candidates for this treatment modality.openBuwenge, Milly; Cammelli, Silvia; Ammendolia, Ilario; Tolento, Giorgio; Zamagni, Alice; Arcelli, Alessandra; Macchia, Gabriella; Deodato, Francesco; Cilla, Savino; Morganti, Alessio G.Buwenge, Milly; Cammelli, Silvia; Ammendolia, Ilario; Tolento, Giorgio; Zamagni, Alice; Arcelli, Alessandra; Macchia, Gabriella; Deodato, Francesco; Cilla, Savino; Morganti, Alessio G

Hypofractionated radiotherapy after conservative surgery may increase low-intermediate grade late fibrosis in breast cancer patients

patients Abstract Fulltext Metrics Get Permission Cite this article Authors Diges\uf9 C, Deodato F, Macchia G, Cilla S, Pieri M, Zamagni A, Farioli A, Buwenge M, Ferrandina G, Morganti AG Received 12 March 2018 Accepted for publication 23 May 2018 Published 3 October 2018 Volume 2018:10 Pages 143\u2014151 DOI https://doi.org/10.2147/BCTT.S167914 Checked for plagiarism Yes Review by Single-blind Peer reviewer comments 3 Editor who approved publication: Professor Pranela Rameshwar Article has an altmetric score of 2 Cinzia Diges\uf9,1 Francesco Deodato,1 Gabriella Macchia,1 Savino Cilla,2 Martina Pieri,3 Alice Zamagni,4 Andrea Farioli,5 Milly Buwenge,4 Gabriella Ferrandina,6,* Alessio G Morganti4,* 1Radiotherapy Unit, General Oncology Unit, Fondazione Giovanni Paolo II, Campobasso, Italy; 2Medical Physics Unit, Fondazione Giovanni Paolo II, Campobasso, Italy; 3Radiotherapy Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy; 4Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy; 5Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; 6Department of Woman and Child Health, Gynecologic Oncology Unit, Fondazione \u201cPoliclinico Universitario A. Gemelli\u201d, IRCSS, Universita\u2019 Cattolica Sacro Cuore, Rome, Italy *These authors contributed equally to this work Aim: To compare late toxicity after postoperative hypofractionated radiotherapy (RT) and standard fractionated RT in patients with early-stage breast carcinoma. Methods: This retrospective study included 447 patients (Modulated Accelerated Radiotherapy [MARA-1]: 317 patients, and control group [CG]: 130 patients). In the CG, the whole breast received 50.4 Gy in 28 fractions (fx) using 3D-radiotherapy, plus a sequential electron boost (10 Gy in 4 fx) to tumor bed. In MARA-1 group, a forward-planned intensity-modulated radiotherapy technique with 40 Gy in 16 fx with a concomitant boost of 4 Gy to breast was used. The primary endpoint was to evaluate late toxicity, and secondary endpoints were acute toxicity, local control, and survival. ClinicalTrials.gov: NCT03461224. Results: Median follow-up was 52 months (range: 3\u2013115 months). Late skin and subcutaneous toxicity were acceptable: 5-year actuarial cumulative incidence of Grade (G) 3 late skin toxicity was 1.5% in CG and 0.0% in MARA-1. Five-year actuarial cumulative incidence of G3 late subcutaneous toxicity was 0.8% in CG and 0.3% in MARA-1. On multivariate analysis, tobacco smoking and planning target volume were associated with an increased risk of late G1 skin toxicity (HR: 2.15, 95% CI: 1.38\u20133.34 and HR: 1.12, 95% CI: 1.07\u20131.18, respectively), whereas patients with a larger planning target volume also showed an increased risk of G1 and G2 late subcutaneous toxicity (HR: 1.14, CI 95%: 1.08\u20131.20 and HR: 1.14, 95% CI: 1.01\u20131.28, respectively). MARA-1 patients also showed an increased risk of late G1 and G2 subcutaneous toxicity (HR: 2.35, 95% CI: 1.61\u20133.41 and HR: 3.07, 95% CI: 1.11\u20138.53, respectively) compared to CG. Conclusion: In this retrospective analysis, postoperative accelerated-hypofractionated RT for early-stage-breast carcinoma was associated with higher incidence of subcutaneous side effects. However, this increase was limited to G1\u2013G2 toxicity. In the future, development of predictive models could help in tailoring dose and fractionation based on the risk of toxicity

Pain Relief after Stereotactic Radiotherapy of Pancreatic Adenocarcinoma: An Updated Systematic Review

Severe pain is frequent in patients with locally advanced pancreatic ductal adenocarcinoma (PDCA). Stereotactic body radiotherapy (SBRT) provides high local control rates in these patients. The aim of this review was to systematically analyze the available evidence on pain relief in patients with PDCA. We updated our previous systematic review through a search on PubMed of papers published from 1 January 2018 to 30 June 2021. Studies with full available text, published in English, and reporting pain relief after SBRT on PDCA were included in this analysis. Statistical analysis was carried out using the MEDCALC statistical software. All tests were two-sided. The I-2 statistic was used to quantify statistical heterogeneity (high heterogeneity level: >50%). Nineteen papers were included in this updated literature review. None of them specifically aimed at assessing pain and/or quality of life. The rate of analgesics reduction or suspension ranged between 40.0 and 100.0% (median: 60.3%) in six studies. The pooled rate was 71.5% (95% CI, 61.6-80.0%), with high heterogeneity between studies (Q(2) test: p < 0.0001; I-2 = 83.8%). The rate of complete response of pain after SBRT ranged between 30.0 and 81.3% (median: 48.4%) in three studies. The pooled rate was 51.9% (95% CI, 39.3-64.3%), with high heterogeneity (Q(2) test: p < 0.008; I-2 = 79.1%). The rate of partial plus complete pain response ranged between 44.4 and 100% (median: 78.6%) in nine studies. The pooled rate was 78.3% (95% CI, 71.0-84.5%), with high heterogeneity (Q(2) test: p < 0.0001; I-2 = 79.4%). A linear regression with sensitivity analysis showed significantly improved overall pain response as the EQD2 alpha/beta:10 increases (p: 0.005). Eight papers did not report any side effect during and after SBRT. In three studies only transient acute effects were recorded. The results of the included studies showed high heterogeneity. However, SBRT of PDCA resulted reasonably effective in producing pain relief in these patients. Further studies are needed to assess the impact of SBRT in this setting based on Patient-Reported Outcomes

Emerging Role of MicroRNAs in the Therapeutic Response in Cervical Cancer: A Systematic Review

Cervical cancer is a common female cancer, with nearly 600,000 cases and more than 300,000 deaths worldwide every year. From a clinical point of view, surgery plays a key role in early cancer management, whereas advanced stages are treated with chemotherapy and/or radiation as adjuvant therapies. Nevertheless, predicting the degree of cancer response to chemotherapy or radiation therapy at diagnosis in order to personalize the clinical approach represents the biggest challenge in locally advanced cancers. The feasibility of such predictive models has been repeatedly assessed using histopathological factors, imaging and nuclear methods, tissue and fluid scans, however with poor results. In this context, the identification of novel potential biomarkers remains an unmet clinical need, and microRNAs (miRNAs) represent an interesting opportunity. With this in mind, the aim of this systematic review was to map the current literature on tumor and circulating miRNAs identified as significantly associated with the therapeutic response in cervical cancer; finally, a perspective point of view sheds light on the challenges ahead in this tumor

Improving total body irradiation with a dedicated couch and 3D-printed patient-specific lung blocks: A feasibility study

Introduction: Total body irradiation (TBI) is an important component of the conditioning regimen in patients undergoing hematopoietic stem cell transplants. TBI is used in very few patients and therefore it is generally delivered with standard linear accelerators (LINACs) and not with dedicated devices. Severe pulmonary toxicity is the most common adverse effect after TBI, and patient-specific lead blocks are used to reduce mean lung dose. In this context, online treatment setup is crucial to achieve precise positioning of the lung blocks. Therefore, in this study we aim to report our experience at generating 3D-printed patient-specific lung blocks and coupling a dedicated couch (with an integrated onboard image device) with a modern LINAC for TBI treatment. Material and methods: TBI was planned and delivered (2Gy/fraction given twice a day, over 3 days) to 15 patients. Online images, to be compared with planned digitally reconstructed radiographies, were acquired with the couch-dedicated Electronic Portal Imaging Device (EPID) panel and imported in the iView software using a homemade Graphical User Interface (GUI). In vivo dosimetry, using Metal-Oxide Field-Effect Transistors (MOSFETs), was used to assess the setup reproducibility in both supine and prone positions. Results: 3D printing of lung blocks was feasible for all planned patients using a stereolithography 3D printer with a build volume of 14.5×14.5×17.5 cm3. The number of required pre-TBI EPID-images generally decreases after the first fraction. In patient-specific quality assurance, the difference between measured and calculated dose was generally<2%. The MOSFET measurements reproducibility along each treatment and patient was 2.7%, in average. Conclusion: The TBI technique was successfully implemented, demonstrating that our approach is feasible, flexible, and cost-effective. The use of 3D-printed patient-specific lung blocks have the potential to personalize TBI treatment and to refine the shape of the blocks before delivery, making them extremely versatile

Measurement of charged particle yields from therapeutic beams in view of the design of an innovative hadrontherapy dose monitor

Particle Therapy (PT) is an emerging technique, which makes use of charged particles to efficiently cure different kinds of solid tumors. The high precision in the hadrons dose deposition requires an accurate monitoring to prevent the risk of under-dosage of the cancer region or of over-dosage of healthy tissues. Monitoring techniques are currently being developed and are based on the detection of particles produced by the beam interaction into the target, in particular: charged particles, result of target and/or projectile fragmentation, prompt photons coming from nucleus de-excitation and back-to-back γ s, produced in the positron annihilation from β + emitters created in the beam interaction with the target. It has been showed that the hadron beam dose release peak can be spatially correlated with the emission pattern of these secondary particles. Here we report about secondary particles production (charged fragments and prompt γ s) performed at different beam and energies that have a particular relevance for PT applications: 12C beam of 80 MeV/u at LNS, 12C beam 220 MeV/u at GSI, and 12C, 4He, 16O beams with energy in the 50–300 MeV/u range at HIT. Finally, a project for a multimodal dose-monitor device exploiting the prompt photons and charged particles emission will be presented

Adaptive Individualized high-dose preoperAtive (AIDA) chemoradiation in high-risk rectal cancer: a phase II trial

Purpose To evaluate the pathological complete response (pCR) rate of locally advanced rectal cancer (LARC) after adaptive high-dose neoadjuvant chemoradiation (CRT) based on (18) F-fluorodeoxyglucose positron emission tomography/computed tomography ((18) F-FDG-PET/CT).Methods The primary endpoint was the pCR rate. Secondary endpoints were the predictive value of (18) F-FDG-PET/CT on pathological response and acute and late toxicity. All patients performed (18) F-FDG-PET/CT at baseline (PET0) and after 2 weeks during CRT (PET1). The metabolic PET parameters were calculated both at the PET0 and PET1. The total CRT dose was 45 Gy to the pelvic lymph nodes and 50 Gy to the primary tumor, corresponding mesorectum, and to metastatic lymph nodes. Furthermore, a sequential boost was delivered to a biological target volume defined by PET1 with an additional dose of 5 Gy in 2 fractions. Capecitabine (825 mg/m(2) twice daily orally) was prescribed for the entire treatment duration.Results Eighteen patients (13 males, 5 females; median age 55 years [range, 41-77 years]) were enrolled in the trial. Patients underwent surgical resection at 8-9 weeks after the end of neoadjuvant CRT. No patient showed grade > 1 acute radiation-induced toxicity. Seven patients (38.8%) had TRG = 0 (complete regression), 5 (27.0%) showed TRG = 2, and 6 (33.0%) had TRG = 3. Based on the TRG results, patients were classified in two groups: TRG = 0 (pCR) and TRG = 1, 2, 3 (non pCR). Accepting p < 0.05 as the level of significance, at the Kruskal-Wallis test, the medians of baseline-MTV, interim-SUVmax, interim-SUVmean, interim-MTV, interim-TLG, and the MTV reduction were significantly different between the two groups. (18) F-FDG-PET/CT was able to predict the pCR in 77.8% of cases through compared evaluation of both baseline PET/CT and interim PET/CT.Conclusions Our results showed that a dose escalation on a reduced target in the final phase of CRT is well tolerated and able to provide a high pCR rate

Development and Validation of a Multi-institutional Nomogram of Outcomes for PSMA-PET-Based Salvage Radiotherapy for Recurrent Prostate Cancer.

IMPORTANCE Prostate-specific antigen membrane positron-emission tomography (PSMA-PET) is increasingly used to guide salvage radiotherapy (sRT) after radical prostatectomy for patients with recurrent or persistent prostate cancer. OBJECTIVE To develop and validate a nomogram for prediction of freedom from biochemical failure (FFBF) after PSMA-PET-based sRT. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study included 1029 patients with prostate cancer treated between July 1, 2013, and June 30, 2020, at 11 centers from 5 countries. The initial database consisted of 1221 patients. All patients had a PSMA-PET scan prior to sRT. Data were analyzed in November 2022. EXPOSURES Patients with a detectable post-radical prostatectomy prostate-specific antigen (PSA) level treated with sRT to the prostatic fossa with or without additional sRT to pelvic lymphatics or concurrent androgen deprivation therapy (ADT) were eligible. MAIN OUTCOMES AND MEASURES The FFBF rate was estimated, and a predictive nomogram was generated and validated. Biochemical relapse was defined as a PSA nadir of 0.2 ng/mL after sRT. RESULTS In the nomogram creation and validation process, 1029 patients (median age at sRT, 70 years [IQR, 64-74 years]) were included and further divided into a training set (n = 708), internal validation set (n = 271), and external outlier validation set (n = 50). The median follow-up was 32 months (IQR, 21-45 months). Based on the PSMA-PET scan prior to sRT, 437 patients (42.5%) had local recurrences and 313 patients (30.4%) had nodal recurrences. Pelvic lymphatics were electively irradiated for 395 patients (38.4%). All patients received sRT to the prostatic fossa: 103 (10.0%) received a dose of less than 66 Gy, 551 (53.5%) received a dose of 66 to 70 Gy, and 375 (36.5%) received a dose of more than 70 Gy. Androgen deprivation therapy was given to 325 (31.6%) patients. On multivariable Cox proportional hazards regression analysis, pre-sRT PSA level (hazard ratio [HR], 1.80 [95% CI, 1.41-2.31]), International Society of Urological Pathology grade in surgery specimen (grade 5 vs 1+2: HR, 2.39 [95% CI, 1.63-3.50], pT stage (pT3b+pT4 vs pT2: HR, 1.91 [95% CI, 1.39-2.67]), surgical margins (R0 vs R1+R2+Rx: HR, 0.60 [95% CI, 0.48-0.78]), ADT use (HR, 0.49 [95% CI, 0.37-0.65]), sRT dose (>70 vs ≤66 Gy: HR, 0.44 [95% CI, 0.29-0.67]), and nodal recurrence detected on PSMA-PET scans (HR, 1.42 [95% CI, 1.09-1.85]) were associated with FFBF. The mean (SD) nomogram concordance index for FFBF was 0.72 (0.06) for the internal validation cohort and 0.67 (0.11) in the external outlier validation cohort. CONCLUSIONS AND RELEVANCE This cohort study of patients with prostate cancer presents an internally and externally validated nomogram that estimated individual patient outcomes after PSMA-PET-guided sRT