A Strategic Approach to Addressing Aggressive Vertebral Hemangiomas With Hypofractionated Stereotactic Body Radiotherapy.

This case report describes the treatment of a recurrent T2 vertebral hemangioma in a 46-year-old man who had prior decompression and fusion surgery. Despite initial stability, the patient developed worsening symptoms, leading to a comprehensive approach involving embolization, microscopic excision, and posterior fixation. Recurrence prompted the choice of Stereotactic Body Radiotherapy (SBRT) over redo surgery. Administered with 30 Gy in five fractions, SBRT significantly reduced hemangioma size and resolved neurological symptoms. The case highlights the effectiveness of hypofractionated SBRT as a promising intervention for aggressive vertebral hemangiomas.

A Japanese multi-institutional phase II study of moderate hypofractionated intensity-modulated radiotherapy with image-guided technique for prostate cancer.

BACKGROUND: The aim of this multi-institutional phase II study was to confirm the safety and the potential efficacy of moderately hypofractionated intensity-modulated radiotherapy (IMRT) with prostate-based image-guidance for Japanese patients. METHODS: Patients with low- or intermediate-risk localized prostate cancer were eligible. Patients with a part of high risk (having only one of the following factors, cT3a, 20 < PSA ≤ 30, or GS = 8 or 9) were also included. Hypofractionated IMRT using daily image-guided technique with prostate matching was performed with a total dose of 70 Gy in 28 fractions. Neoadjuvant hormonal therapy for 4-8 months was mandatory for patients with intermediate or high-risk prostate cancer. RESULTS: From 20 institutions, 134 patients enrolled. The median follow-up was 5.16 years (range, 1.43-6.47 years). The number of patients with low, intermediate, and high-risk prostate cancer was 20, 80, and 34, respectively. The 5-year overall, biochemical failure-free, and clinical failure-free survival was 94.5%, 96.0%, and 99.2%, respectively. The 5-year biochemical failure-free survival for patients with low-, intermediate-, and high-risk disease was 94.1%, 97.4%, and 93.9%, respectively. The incidences of grade 2 gastrointestinal (GI) and genitourinary (GU) late toxicities at 5 years were 5.3% and 5.3%, respectively. There are no acute or late toxicities ≥ grade 3. Of 124 patients who were followed for up to 5 years, the grade 2 late GU or GI toxicities were 10.5% (90% confidence intervals, 6.3-16.2%, p = 0.0958). CONCLUSION: The safety and efficacy of moderately hypofractionated IMRT with prostate-based image-guidance was confirmed among Japanese patients with prostate cancer.

Photon vs proton hypofractionation in prostate cancer: A systematic review and meta-analysis.

BACKGROUND: High-level evidence on hypofractionated proton therapy (PT) for localized and locally advanced prostate cancer (PCa) patients is currently missing. The aim of this study is to provide a systematic literature review to compare the toxicity and effectiveness of curative radiotherapy with photon therapy (XRT) or PT in PCa. METHODS: PubMed, Embase, and the Cochrane Library databases were systematically searched up to April 2022. Men with a diagnosis of PCa who underwent curative hypofractionated RT treatment (PT or XRT) were included. Risk of grade (G) ≥ 2 acute and late genitourinary (GU) OR gastrointestinal (GI) toxicity were the primary outcomes of interest. Secondary outcomes were five-year biochemical relapse-free survival (b-RFS), clinical relapse-free, distant metastasis-free, and prostate cancer-specific survival. Heterogeneity between study-specific estimates was assessed using Chi-square statistics and measured with the I2 index (heterogeneity measure across studies). RESULTS: A total of 230 studies matched inclusion criteria and, due to overlapped populations, 160 were included in the present analysis. Significant lower rates of G ≥ 2 acute GI incidence (2 % vs 7 %) and improved 5-year biochemical relapse-free survival (95 % vs 91 %) were observed in the PT arm compared to XRT. PT benefits in 5-year biochemical relapse-free survival were maintained for the moderate hypofractionated arm (p-value 0.0122) and among patients in intermediate and low-risk classes (p-values < 0.0001 and 0.0368, respectively). No statistically relevant differences were found for the other considered outcomes. CONCLUSION: The present study supports that PT is safe and effective for localized PCa treatment, however, more data from RCTs are needed to draw solid evidence in this setting and further effort must be made to identify the patient subgroups that could benefit the most from PT.

Hypofractionation for Regional Nodal Irradiation in Breast Cancer: Best of Both the Worlds.

Locoregional radiotherapy play an important role in controlling the disease after surgery in patients with breast cancer. Radiotherapy schedules vary from conventional fraction to hypofractionation. The purpose of this review is to get an insight into the data on regional nodal irradiation (RNI) with hypofractionation in patients with breast cancer. This systematic review was constructed in accordance with Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) framework. Electronic databases such as PubMed, Cochrane and EMBASE were searched from January 1, 2023 to March 31, 2023 to identify studies published in English language on hypofractionated RNI in post mastectomy patients. The search was carried out with the National Library of Medicine's Medical Subject Heading (MeSH) terms like "regional nodal irradiation," "hypofractionated" and "hypofractionation in breast cancer" with different Boolean operators (and/or). A manual search of reference lists of included articles was also performed to make sure there were no additional cases unidentified from the primary search. Studies deemed potentially eligible were identified and assessed by same independent reviewers to confirm eligibility. RNI data are mainly from a randomized study from Beijing and pooled data from START trials. There are also data from retrospective and single institutional studies and a few phase II studies with limited number of patients using different dose fractionations and techniques of radiotherapy. Doses used in these trials ranged from 26-47.7 Gy in 5-19 fractions over 1-4 weeks. Grade ≥ 2 pulmonary fibrosis and lymphedema rate ranged from 2%-7.9% and 3%-19.8% respectively. Grade ≥ 2 shoulder dysfunction and brachial plexopathy ranged from 0.2%-28% and 0%-< 1%, respectively. Late effects with a dose range of 26-40 Gy delivered in 5 to 15 fractions over 1-3 weeks were less/similar to conventional fraction. Current data showed lower/similar rates of toxicity with hypofractionated RNI compared with conventional fractionation RNI. Doses of 26 Gy to 40 Gy delivered in 5 to 15 fractions over 1-3 weeks are safe for RNI. With limited data, ultra-hypofractionation 26 Gy/5 fractions/1 week also seems to be safe. However, long-term outcome is awaited and many trials are going on to address its efficacy and safety.

Toxicity evaluation of dose-escalation in hypofractionated regional nodal irradiation for breast cancer: a retrospective study.

PURPOSE: Regional nodal irradiation (RNI) to the axilla and supraclavicular area presents distinct toxicities, such as lymphedema and shoulder stiffness, compared to whole-breast irradiation. There is insufficient evidence on the safety of dose-escalation in hypofractionated RNI. We aimed to evaluate and compare toxicity rates in patients with breast cancer who received hypofractionated RNI with and without dose-escalation. METHODS: We retrospectively analyzed 381 patients with breast cancer treated with hypofractionated RNI between March 2015 and February 2017. Patients received either the standard-dose to the regional nodal area (43.2 Gy/16 fx; 48.7 Gy3.5 EQD2, 2 Gy equivalent dose with α/ß=3.5 Gy) or dose-escalation with a median dose of 54.8 Gy3.5 EQD2 (range, 51.7 - 60.9 Gy3.5 EQD2) depending on clinical and pathologic nodal stage. Toxicity rates of lymphedema and shoulder stiffness were assessed, and statistical analyses were conducted to identify associated factors. RESULTS: The median follow-up time was 32.3 months (5.7 - 47.0 months). After radiotherapy, 71 (18.6%) patients developed lymphedema, and 48 (12.6%) developed shoulder stiffness. Patients who received dose-escalation exhibited significantly higher rates of lymphedema (32.1% vs. 14.8%; Odds Ratio (OR): 2.72, p=0.0004) and shoulder stiffness (23.8% vs. 9.4%; OR: 2.01, p=0.0205) compared to the standard-dose group. Moreover, dose-escalation showed a tendency to increase the severity of lymphedema and shoulder stiffness. CONCLUSIONS: Patients who received dose-escalation in hypofractionated RNI face a higher risk of developing lymphedema and shoulder stiffness compared to those who received standard-dose hypofractionated RNI. Therefore, it is crucial to implement close and frequent monitoring for early detection, along with timely rehabilitation interventions for these patients.

Systematic Review of Hypofractionated Radiation Therapy for the Treatment of Oesophageal Squamous Cell Carcinoma and Oesophageal Adenocarcinoma.

BACKGROUND AND AIM: There has been limited progress made in improving the suboptimal outcomes delivered by conventionally fractionated radiotherapy (RT) for oesophageal adenocarcinoma (OAC) and squamous cell carcinoma (OSCC). A greater biological effect may be achieved using hypofractionated RT (HFRT), though the toxicity, tolerability and efficacy of this approach in OAC and OSCC is uncertain. METHODS: A systematic literature review was carried out in accordance with Preferred Reporting Items for Systematic Reviews guidance. Medline, EMBASE, PubMed, Cochrane, CINAHL, Scopus and Web of Science databases were searched for terms relating to HFRT (>2.4Gy per fraction) for OAC or OSCC. All relevant clinical studies published between January 2000 and April 2023 were included. Study quality was assessed using predefined criteria. RESULTS: Ninety-six studies were screened and 20 subsequently included, together incorporating 1208 patients. Fourteen studies focussed on neoadjuvant or definitive treatment. These were predominantly retrospective (n = 10, 71%) though two (n = 2, 14%) early phase trials were identified. Most focussed on OSCC (n = 7, 47%) or mixed OSCC/OAC (n = 6, 43%) populations. Four (28.6%) included a conventionally fractionated chemoradiotherapy (CRT) comparator, against which median overall (mOS) and progression free survival outcomes from HFRT did not differ. Reported mOS for HFRT ranged between 29-36 months at 2.5-3.125Gy per fraction (total dose 50-60Gy) for OAC and OSCC combined. Toxicity and tolerability with HFRT was comparable with conventionally fractionated CRT up to, but not exceeding, 5Gy. Three (50%) of the six palliative-intent studies were early phase trials and most (n = 4, 67%) focussed on OAC and OSCC. Response rates with HFRT in the palliative setting were 63.6-88.0%. CONCLUSION: These data provide evidence in OAC/OSCC for promising efficacy and an acceptable toxicity profile for moderately HFRT, alone or with concurrent chemotherapy. These data should prompt prospective, randomised comparisons of HFRT and conventionally fractionated CRT and single-modality RT schedules. REGISTRATION DETAILS: PROSPERO; CRD42023457791.

The impact of advancing the standard of care in radiotherapy on operational treatment resources.

PURPOSE: To demonstrate the impact of implementing hypofractionated prescription regimens and advanced treatment techniques on institutional operational hours and radiotherapy personnel resources in a multi-institutional setting. The study may be used to describe the impact of advancing the standard of care with modern radiotherapy techniques on patient and staff resources. METHODS: This study uses radiation therapy data extracted from the radiotherapy information system from two tertiary care, university-affiliated cancer centers from 2012 to 2021. Across all patients in the analysis, the average fraction number for curative and palliative patients was reported each year in the decade. Also, the institutional operational treatment hours are reported for both centers. A sub-analysis for curative intent breast and lung radiotherapy patients was performed to contextualize the impact of changes to imaging, motion management, and treatment technique. RESULTS: From 2012 to 2021, Center 1 had 42 214 patient plans and Center 2 had 43 252 patient plans included in the analysis. Averaged over both centers across the decade, the average fraction number per patient decreased from 6.9 to 5.2 (25%) and 21.8 to 17.2 (21%) for palliative and curative patients, respectively. The operational treatment hours for both institutions increased from 8 h 15 min to 9 h 45 min (18%), despite a patient population increase of 45%. CONCLUSION: The clinical implementation of hypofractionated treatment regimens has successfully reduced the radiotherapy workload and operational treatment hours required to treat patients. This analysis describes the impact of changes to the standard of care on institutional resources.

Impact of daily plan adaptation on accumulated doses in ultra-hypofractionated magnetic resonance-guided radiation therapy of prostate cancer.

Background and purpose: Ultra-hypofractionated online adaptive magnetic resonance-guided radiotherapy (MRgRT) is promising for prostate cancer. However, the impact of online adaptation on target coverage and organ-at-risk (OAR) sparing at the level of accumulated dose has not yet been reported. Using deformable image registration (DIR)-based accumulation, we compared the delivered adapted dose with the simulated non-adapted dose. Materials and methods: Twenty-three prostate cancer patients treated at two clinics with 0.35 T magnetic resonance-guided linear accelerator (MR-linac) following the same treatment protocol (5 × 7.5 Gy with urethral sparing and daily adaptation) were included. The fraction MR images were deformably registered to the planning MR image. Both non-adapted and adapted fraction doses were accumulated with the corresponding vector fields. Two DIR approaches were implemented. PTV* (planning target volume minus urethra+2mm) D95%, CTV* (clinical target volume minus urethra) D98%, and OARs (urethra+2mm, bladder, and rectum) D0.2cc, were evaluated. Statistical significance was inferred from a two-tailed Wilcoxon signed-rank test (p < 0.05). Results: Normalized to the baseline, the accumulated PTV* D95% increased significantly by 2.7 % ([1.5, 4.3]%) through adaptation, and the CTV* D98% by 1.2 % ([0.1, 1.7]%). For the OARs after adaptation, accumulated bladder D0.2cc decreased by 0.4 % ([-1.2, 0.4]%), urethra+2mmD0.2cc by 0.8 % ([-1.6, -0.1]%), while rectum D0.2cc increased by 2.6 % ([1.2, 4.9]%). For all patients, rectum D0.2cc was still below the clinical constraint. Results of both DIR approaches differed on average by less than 0.2 %. Conclusions: Online adaptation in MRgRT improved target coverage and OARs sparing at the level of accumulated dose.

Personalized radiation therapy for glioblastoma.

Glioblastoma is the most common primary brain tumor with an estimated 14,000 Americans diagnosed with this disease annually. This disease is treated with maximal surgical resection followed by adjuvant radiation therapy. Radiation therapy was initially delivered to the whole brain and with no concurrent or adjuvant systemic therapy. Advances in imaging and treatment delivery have allowed for partial brain irradiation to minimize radiation dose to normal structures, as well as sparing structures important for memory such as the hippocampus, decreasing morbidity and toxicity. While there is no consensus on the optimal radiation volume needed to successfully treat glioblastoma, there is consensus that the tumor bed with margin is preferable to treatment of the whole brain. Additionally, advances in knowledge regarding tumor biology have demonstrated the benefit of concurrent and adjuvant chemotherapy, as well as demonstrated that methylation of genes in the tumor can predispose greater responsiveness to chemotherapy. The following review describes the advancements in specific radiation techniques that have been used to improve the therapeutic ratio for management of glioblastoma and methods used to personalize radiation treatment for patients based on genomic markers as well as clinical factors. The review also describes future investigations that are currently taking place in order to enable a further improvement of clinical outcomes for patients with glioblastoma.

Adaptive ultra-hypofractionated whole-pelvic radiotherapy in high-risk and very high-risk prostate cancer on 1.5-Tesla MR-Linac: Estimated delivered dose and early toxicity results.

Background: Magnetic resonance (MR)-guided ultra-hypofractionated radiotherapy with whole-pelvic irradiation (UHF-WPRT) is a novel approach to radiotherapy for patients with high-risk (HR) and very high-risk (VHR) prostate cancer (PCa). However, the inherent complexity of adaptive UHF-WPRT might inevitably result in longer on-couch time. We aimed to estimate the delivered dose, study the feasibility and safety of adaptive UHF-WPRT on a 1.5-Tesla MR-Linac. Methods: Ten patients with clinical stage T3a-4N0-1M0-1c PCa, who consecutively received UHF-WPRT, were enrolled prospectively. The contours of the target and organ-at-risks on the position verification-MR (PV-MR), beam-on 3D-MR(Bn-MR), and post-MR (after radiotherapy delivery) were derived from the pre-MR data by deformable image registration. The physician then manually adjusted them, and dose recalculation was performed accordingly. GraphPad Prism 9 (GraphPad Prism Software Inc.) was utilized for conducting statistical analyses. Results: In total, we collected 188 MR scans (50 pre-MR, 50 PV-MR, 44 Bn-MR, and 44 post-MR scans). With median 59 min, the mean prostate clinical target volume (CTV)-V100% was 98.59% ± 2.74%, and the mean pelvic CTVp-V100% relative percentages of all scans was 99.60% ± 1.18%. The median V29 Gy change in the rectal wall was -2% (-18% to 20%). With a median follow-up of 9 months, no patient had acute Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or more severe genitourinary (GU) or gastrointestinal (GI) toxicities (0%). Conclusion: UHF-RT to the prostate and the whole pelvis with concomitant boost to positive nodes using an Adapt-To-Shape (ATS) workflow was technically feasible for patients with HR and VHR PCa, presenting only mild GU and GI toxicities. The estimated target dose during the beam-on phase was clinically acceptable based on the 3D-MR-based dosimetry analysis. Clinical trial registration: Chinese Clinical Trial Registry ChiCTR2000033382.

Update on Dosing and Fractionation for Neoadjuvant Radiotherapy for Localized Soft Tissue Sarcoma.

OPINION STATEMENT: Neoadjuvant radiotherapy (RT) over 5-6 weeks with daily doses of 1.8-2.0 Gy to a total dose of 50-50.4 Gy is standard of care for localized high-grade soft tissue sarcomas (STS) of the extremities and trunk wall. One exception is myxoid liposarcomas where the phase II DOREMY trial applying a preoperative dose of 36 Gy in 2 Gy fractions (3-4 weeks treatment) has achieved excellent local control rates of 100% after a median follow-up of 25 months.Hypofractionated preoperative RT has been investigated in a number of phase II single-arm studies suggesting that daily doses of 2.75-8 Gy over 1-3 weeks can achieve similar oncological outcomes to conventional neoadjuvant RT. Prospective data with direct head-to-head comparison to conventional neoadjuvant RT investigating oncological outcomes and toxicity profiles is eagerly awaited.For the entire group of retroperitoneal sarcomas, RT is not the standard of care. The randomized multi-center STRASS trial did not find a benefit in abdominal recurrence-free survival by the addition of preoperative RT. However, for the largest histological subgroup of well-differentiated and grades I and II dedifferentiated liposarcomas, the STRASS trial and the post-hoc propensity-matched STREXIT analysis have identified a possible benefit in survival by preoperative RT. These patients deserve to be informed about the pros and cons of preoperative RT while the longer follow-up data from the STRASS trial is awaited.

Preliminary results of hypofractionated radiotherapy in breast cancer in Chandigarh, India: single-centre, non-inferiority, open-label, randomised, phase 3 trial.

Background: Globally, most of the randomised trials with hypofractionation in patients with breast cancer have used 3-dimensional conformal radiotherapy technique (3D-CRT). As facilities for 3D-CRT technique may not be available in low-resource settings, there is a need to see if hypofractionation is feasible and safe with 2-dimensional (2-D) technique. In this study, we compared a 3-week radiation schedule with a 2-week schedule of hypofractionated radiotherapy in patients with breast cancer with 2-D technique. Methods: The current study was an open-label, randomised, phase 3 trial. Patients with breast cancer, stage I-III, post mastectomy or after breast conservative surgery who needed adjuvant locoregional radiotherapy were randomised in the Department of Radiotherapy & Oncology, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, India; to 34Gy in 10 fractions over 2 weeks (2-week arm) or 35Gy in 15 fractions over 3 weeks to the chest wall and 40Gy/15#/3wks to breast and supraclavicular fossa (3-week arm). Boost dose when indicated was 8-10Gy/2-4#/2-4 days in both the arms. Patients were planned on a 2-dimensional (2D) simulator with 2 tangential fields to breast/chest wall and incident supraclavicular fossa field. Acute toxicity was assessed using the Radiation Therapy Oncology Group (RTOG) grading scale. Assessments were carried out weekly during radiotherapy and at 4 weeks after treatment by the physician. Cosmetic outcome was assessed using the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/RTOG scale. The toxicity rates between the two arms were compared using Fisher's exact tests. The trial was approved by institutional ethics committee and registered with ClinicalTrials.gov, number NCT04075058. Findings: This study included 1121 eligible patients from June 2015 to December 2020. Median follow-up was 35 months (6-84 months). Mean age was 48 years (24-75 years). The patient characteristics were comparable between the two arms except for more mastectomies in the 3-week arm and more node-positive patients in the 2-week arm. There were more oestrogen receptor-positive tumors in the 3-week arm. Acute skin toxicities were comparable between the two arms. Grade 2 and 3 skin toxicity was 100 (18%) and 82 (15%); and 16 (3%) and 12 (2%) in the 3-week and 2-week arm (p = 0.21), respectively. Cosmetic outcome was assessed as Excellent or Good for 89% of patients in the 3-week arm as compared to 94% in the 2-week arm (p = 0.004). Interpretation: The two radiation schedules were comparable in terms of acute skin toxicity. The cosmetic outcome was better with the 2-week schedule. The preliminary findings indicate 2-week radiotherapy schedule with 2-D technique was better than the 3-week schedule in patients with breast cancer. However, disease outcomes and late-term toxicities need to be further checked. Funding: This study was funded by Science and Engineering Research Board (SERB), India.

Changing trends in the management of ductal carcinoma in situ in Republic of Korea: a comprehensive analysis using Health Insurance Review and Assessment data [2009-2020].

Background: Increasing rates of diagnosis of ductal carcinoma in situ (DCIS), given the widespread use of mammography, is a global trend. Various attempts have been made in the selection of surgical methods and application of radiation therapy (RT), and the prevalence of infectious diseases has also affected these attempts. This study aimed to investigate evolving treatment patterns and trends in the management of DCIS in South Korea. Methods: We conducted a comprehensive search of the Korean Health Insurance Review and Assessment Service-National Patient Sample (HIRA-NPS) database and selected patients who underwent breast surgery following a DCIS diagnosis between 2009 and 2020. Based on this sample, the analyses were weighted according to the Korean population. We examined annual variations in mastectomy types, reconstructive procedures, and RT utilization from a multidisciplinary perspective. Results: In our weighted sample, 43,780 patients with DCIS underwent surgery, with a consistent annual increase of 10%. The proportion of lumpectomy procedures increased from 56.7% to 65.4%, showing a greater growth rate than that of total mastectomies (TMs). Following the availability of reconstruction data in 2015, shifts have emerged toward a preference for implant-based autologous tissue reconstruction. As we transitioned to the latter part of our study, the trend was marked by the increasing adoption of hypofractionated RT and omission of RT. Of the patients who underwent lumpectomy in 2020, 25.6% adopted hypofractionated RT and 53.8% omitted RT. This transformation was particularly evident among older patients, individuals treated in metropolitan areas, and those treated in small-sized healthcare facilities. Conclusions: Our study sheds light on the changing landscape of DCIS treatment in South Korea incorporating perspectives from surgeons, plastic surgeons, and radiation oncologists. We observed an increase in the rates of lumpectomy and implant-based reconstruction. Adoption of hypofractionated RT and omission of RT showed increasing trends.

Ultra-hypofractionated one-week locoregional radiotherapy for patients with early breast cancer: Acute toxicity results.

Purpose: Moderate hypofractionated radiotherapy is the standard of care for all patients with breast cancer, irrespective of stage or prior treatments. While extreme hypofractionation is accepted for early-stage tumours, its application in irradiating locoregional lymph nodes remains controversial. Materials and methods: A prospective registry analysis from July 2020 to September 2023 included 276 patients with early-stage breast cancer treated with one-week ultra-hypofractionation (UHF) at 26 Gy in 5 fractions on the whole breast (58.3 %) or thoracic wall (41.7 %) and ipsilateral regional lymph nodes and simultaneous integrated boost (58.3 %). Primary endpoint was assessment of acute adverse events (AEs). Secondarily, onset of early-delayed toxicity was assessed. A minimum 6-month follow-up was required for assessing potential treatment-related early-delayed complications. Acute or late complications attributable to treatment were assessed at inclusion using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria. Results: With a median follow-up of 19 months (range 1-49 months), 159 (57.6 %) patients reported AEs, predominantly grade (G) 1 (n = 139, 50.4 %) and G2 (n = 20, 7.8 %). Skin acute toxicity was common (G1/2: 134, G3: 14), while breast oedema occurred in 10 patients (G1: 9, G2: 1), and 15.9 % reported breast pain (G1: 42, G2: 2). Ipsilateral arm oedema was observed in 1.8 % patients. For patients with a follow-up beyond 6 months (n = 213), 23.4 % patients reported G1/G2 skin AEs, 8.8 % had G1/G2 breast/chest wall oedema, and 8.9 % experienced arm lymphedema. There were no cases of brachial plexopathy or G3 toxicity in this group of patients. Conclusions: One-week UHF adjuvant locoregional radiation is well-tolerated, displaying low-toxicity profiles comparable to other studies using similar irradiation schedules.

A multicenter high-quality data registry for advanced proton therapy approaches: the POWER registry.

BACKGROUND: Paucity and low evidence-level data on proton therapy (PT) represent one of the main issues for the establishment of solid indications in the PT setting. Aim of the present registry, the POWER registry, is to provide a tool for systematic, prospective, harmonized, and multidimensional high-quality data collection to promote knowledge in the field of PT with a particular focus on the use of hypofractionation. METHODS: All patients with any type of oncologic disease (benign and malignant disease) eligible for PT at the European Institute of Oncology (IEO), Milan, Italy, will be included in the present registry. Three levels of data collection will be implemented: Level (1) clinical research (patients outcome and toxicity, quality of life, and cost/effectiveness analysis); Level (2) radiological and radiobiological research (radiomic and dosiomic analysis, as well as biological modeling); Level (3) biological and translational research (biological biomarkers and genomic data analysis). Endpoints and outcome measures of hypofractionation schedules will be evaluated in terms of either Treatment Efficacy (tumor response rate, time to progression/percentages of survivors/median survival, clinical, biological, and radiological biomarkers changes, identified as surrogate endpoints of cancer survival/response to treatment) and Toxicity. The study protocol has been approved by the IEO Ethical Committee (IEO 1885). Other than patients treated at IEO, additional PT facilities (equipped with Proteus®ONE or Proteus®PLUS technologies by IBA, Ion Beam Applications, Louvain-la-Neuve, Belgium) are planned to join the registry data collection. Moreover, the registry will be also fully integrated into international PT data collection networks.

Hypofractionated Partial Breast Irradiation With Intensity-Modulated Radiotherapy in Early Breast Cancer or Carcinoma In Situ: An Investigational Short-Term Analysis.

PURPOSE: This study aimed to analyze the treatment outcomes and adverse effects of moderately hypofractionated partial breast irradiation (PBI) in patients with early breast cancer. METHODS: In total, 473 patients with early breast cancer or carcinoma in situ were diagnosed with Tis or T1N0 disease and underwent PBI following breast-conserving surgery. All histologic tumor types, close surgical margins within 1 mm of the tumor, and multifocal tumors were included in this study. A radiation dose of 50 Gy in 20 fractions was delivered over 4 weeks using intensity-modulated radiotherapy technique. Dosimetric data, recurrence patterns, survival outcomes, and adverse events were retrospectively analyzed. RESULTS: During a median follow-up of 28.9 months, seven patients (1.5%) experienced ipsilateral breast tumor recurrence (IBTR). Two patients had regional recurrence, four patients developed contralateral breast cancer, and no distant metastases were observed. The locoregional recurrence rate in the ipsilateral breast was 1.8%. Two deaths occurred during the follow-up period, but were not attributed to breast cancer. The 2-year disease-free survival and 2-year overall survival rates were was 94.0% and 99.8%, respectively. Acute adverse events occurred in 131 patients (27.1%), and were distributed among all grades, with only two patients (0.4%) experiencing grade 3 events. Late adverse events were noted in 16 patients (3.4%), and were distributed among all grades, including grade 3 events in four patients (0.8%). No grade 4 or 5 events were observed. CONCLUSION: Hypofractionated PBI demonstrated favorable IBTR rates in patients with early breast cancer, with low incidence of acute and late toxicities in the short-term analysis.

Evidence-based clinical recommendations for hypofractionated radiotherapy: exploring efficacy and safety - Part 1. Brain and head and neck.

Advances in radiotherapy (RT) techniques, including intensity-modulated RT and image-guided RT, have allowed hypofractionation, increasing the fraction size over the conventional dose of 1.8-2.0 Gy. Hypofractionation offers advantages such as shorter treatment times, improved compliance, and under specific conditions, particularly in tumors with a low α/ß ratio, higher efficacy. It was initially explored for use in RT for prostate cancer and adjuvant RT for breast cancer, and its application has been extended to various other malignancies. Hypofractionated RT (HFRT) may also be effective in patients who are unable to undergo conventional treatment owing to poor performance status, comorbidities, or old age. The treatment of brain tumors with HFRT is relatively common because brain stereotactic radiosurgery has been performed for over two decades. However, re-irradiation of recurrent lesions and treatment of elderly or frail patients are areas under investigation. HFRT for head and neck cancer has not been widely used because of concerns regarding late toxicity. Thus, we aimed to provide a comprehensive summary of the current evidence for HFRT for brain tumors and head and neck cancer and to offer practical recommendations to clinicians faced with the challenge of choosing new treatment options.

Hypofractionated Radiotherapy as a Standalone Treatment Modality for Locally Advanced Type B2 Thymoma in an Octogenarian Patient: 45 Gy in 15 Fractions.

Thymic epithelial tumors (TETs), particularly type B2 thymomas, are rare neoplasms primarily found in the anterior mediastinum. The current therapeutic approach includes surgery, chemotherapy, and radiotherapy, but there is limited research on radiotherapy as a standalone treatment. This case report aims to elucidate the clinical outcomes of hypofractionated radiotherapy as a standalone treatment for locally advanced type B2 thymoma, offering insights into its potential efficacy and role in clinical practice.

A hypoxia biomarker does not predict benefit from giving chemotherapy with radiotherapy in the BC2001 randomised controlled trial.

BACKGROUND: BC2001 showed combining chemotherapy (5-FU + mitomycin-C) with radiotherapy improves loco-regional disease-free survival in patients with muscle-invasive bladder cancer (MIBC). We previously showed a 24-gene hypoxia-associated signature predicted benefit from hypoxia-modifying radiosensitisation in BCON and hypothesised that only patients with low hypoxia scores (HSs) would benefit from chemotherapy in BC2001. BC2001 allowed conventional (64Gy/32 fractions) or hypofractionated (55Gy/20 fractions) radiotherapy. An exploratory analysis tested an additional hypothesis that hypofractionation reduces reoxygenation and would be detrimental for patients with hypoxic tumours. METHODS: RNA was extracted from pre-treatment biopsies (298 BC2001 patients), transcriptomic data generated (Affymetrix Clariom-S arrays), HSs calculated (median expression of 24-signature genes) and patients stratified as hypoxia-high or -low (cut-off: cohort median). PRIMARY ENDPOINT: invasive loco-regional control (ILRC); secondary overall survival. FINDINGS: Hypoxia affected overall survival (HR = 1.30; 95% CI 0.99-1.70; p = 0.062): more uncertainty for ILRC (HR = 1.29; 95% CI 0.82-2.03; p = 0.264). Benefit from chemotherapy was similar for patients with high or low HSs, with no interaction between HS and treatment arm. High HS associated with poor ILRC following hypofractionated (n = 90, HR 1.69; 95% CI 0.99-2.89 p = 0.057) but not conventional (n = 207, HR 0.70; 95% CI 0.28-1.80, p = 0.461) radiotherapy. The finding was confirmed in an independent cohort (BCON) where hypoxia associated with a poor prognosis for patients receiving hypofractionated (n = 51; HR 14.2; 95% CI 1.7-119; p = 0.015) but not conventional (n = 24, HR 1.04; 95% CI 0.07-15.5, p = 0.978) radiotherapy. INTERPRETATION: Tumour hypoxia status does not affect benefit from BC2001 chemotherapy. Hypoxia appears to affect fractionation sensitivity. Use of HSs to personalise treatment needs testing in a biomarker-stratified trial. FUNDING: Cancer Research UK, NIHR, MRC.

Outcomes of whole breast radiation therapy in Asian breast cancer patients with prior cosmetic implants.

BACKGROUND: As breast augmentation has become more popular, an increasing number of women with augmented breasts require treatment for breast cancer. This study aimed to assess the outcomes of postoperative whole breast radiation therapy (WB-RT) in Asian patients with breast cancer who underwent prior cosmetic breast implantation. METHODS: We retrospectively reviewed the medical records of 61 patients with breast cancer who had prior cosmetic breast implants (prior-CBI) and underwent breast-conserving surgery (BCS) and WB-RT between 2015 and 2020. The median implant volume was 238.8 cc, with a median interval of 84.7 months between the prior-CBI and BCS. WB-RT was administered with either conventional fractionation (CF-RT) at 50 Gy in 25 fractions (N = 36) or hypofractionation (HF-RT) at 42.6 Gy in 16 fractions (N = 25). The incidences of implant-related complications (IRC) and their contributing factors were analyzed. RESULTS: After a median follow-up of 43.5 months, the 3-year cumulative incidences of IRC and implant loss were 17.2% and 4.9%, respectively. Among the four (6.6%) patients who opted for implant removal after RT, three were potentially related to RT-related capsular contracture. There was no difference in the 3-year cumulative IRC rates following CF-RT and HF-RT (12.2% and 26.7%, respectively; p = 0.120). The risk factors for IRC included a larger implant size (> 260 cc) and a higher ratio of breast tissue to implant volume. CONCLUSIONS: This study demonstrated a favorable safety profile of WB-RT for treatment of breast cancer in Asian women with prior-CBI. The integration of HF-RT following BCS was thought to be a feasible approach.