Disease control outcomes of stereotactic body radiation therapy or moderate hypo-fractionation for prostate cancer: Real-world experience at two Canadian centers.

BACKGROUND: Advantages of using stereotactic body radiation therapy to treat prostate cancer include short treatment times, decreased costs, and limited toxicity. Randomized trial outcomes comparing 5-fraction stereotactic body radiation therapy to conventionally fractionated radiotherapy or hypo-fractionated radiation therapy are pending. OBJECTIVE: We report the 10-year experience with 5-fraction stereotactic body radiation therapy and hypo-fractionated radiation therapy at two Canadian centers. MATERIAL AND METHODS: Patients with low- or intermediate-risk prostate cancer treated with stereotactic body radiation therapy alone (35-40 Gy in 5 fractions) or hypo-fractionated radiation therapy alone (60-62 Gy in 20 fractions) in the period of July 2010 and June 2020. The biochemical relapse-free survival, PSA nadir, interval time to PSA nadir, time to biochemical recurrence (2 ng/ml above PSA nadir) and overall survival were reviewed. Outcomes between treatment groups were compared after propensity-matching by patient baseline characteristics. Kaplan-Meier curves were used to assess biochemical relapse-free survival and overall survival. RESULTS: We identified 205 and 513 patients with low or intermediate-risk prostate cancer who were treated with stereotactic body radiation therapy or hypo-fractionation, respectively. Intermediate-risk category composed 81% and 95% of the stereotactic body radiation therapy and hypo-fractionated radiation therapy cohorts, respectively. After a median follow up of 58.6 months for the stereotactic body radiation therapy cohort and 45.0 months for the hypo-fractionated cohort, biochemical relapse-free survival and overall survival were not significantly different between treatment groups. The 5-year biochemical relapse-free survival rates were 92.1% and 93.6% and overall survival rates were 96.4% and 95.0% for the stereotactic body radiation therapy and hypo-fractionated cohorts, respectively, after propensity-matching. Stereotactic body radiation therapy resulted in a significantly lower PSA nadir (0.18 ng/ml) compared to hypo-fractionated radiation therapy (0.48 ng/ml) in patients with low-risk prostate cancer. Mean time to biochemical recurrence was not different between treatment groups. CONCLUSIONS: Stereotactic body radiation therapy is an effective treatment option for low and intermediate-risk prostate cancer with encouraging biochemical relapse-free survival and overall survival rates comparable with hypo-fractionated radiation therapy.

Single-cell RNA sequencing reveals recruitment of the M2-like CCL8high macrophages in Lewis lung carcinoma-bearing mice following hypofractionated radiotherapy.

BACKGROUND: Tumor-associated macrophages (TAMs) play a pivotal role in reshaping the tumor microenvironment following radiotherapy. The mechanisms underlying this reprogramming process remain to be elucidated. METHODS: Subcutaneous Lewis lung carcinoma (LLC) murine model was treated with hypofrationated radiotherapy (8 Gy × 3F). Single-cell RNA sequencing was utilized to identify subclusters and functions of TAMs. Multiplex assay and enzyme-linked immunosorbent assay (ELISA) were employed to measure serum chemokine levels. Bindarit was used to inhibit CCL8, CCL7, and CCL2. The infiltration of TAMs after combination treatment with hypofractionated radiotherapy and Bindarit was quantified with flow cytometry, while the influx of CD206 and CCL8 was assessed by immunostaining. RESULTS: Transcriptome analysis identified a distinct subset of M2-like macrophages characterized by elevated Ccl8 expression level following hypofractionated radiotherapy in LLC-bearing mice. Remarkbly, hypofractionated radiotherapy not only promoted CCL8high macrophages infiltration but also reprogrammed them by upregulating immunosuppressive genes, thereby fostering an immunosuppressive tumor microenvironment. Additioinally, hypofractionated radiotherapy enhanced the CCL signaling pathway, augmenting the pro-tumorigenic functions of CCL8high macrophages and boosting TAMs recruitment. The adjunctive treatment combining hypofractionated radiotherapy with Bindarit effectively reduced M2 macrophages infiltration and prolonged the duration of local tumor control. CONCLUSIONS: Hypofractionated radiotherapy enhances the infiltration of CCL8high macrophages and amplifies their roles in macrophage recruitment through the CCL signaling pathway, leading to an immunosuppressive tumor microenvironment. These findings highlight the potential of targeting TAMs and introduces a novel combination to improve the efficacy of hypofractionated radiotherapy.

Efficacy and safety analysis of hypofractionated and conventional fractionated radiotherapy in postoperative breast cancer patients.

OBJECTIVES: In this meta-analysis, we conducted a comparative analysis of the safety and efficacy of hypofractionated and conventional fractionated radiotherapy in individuals who had undergone surgery for breast cancer. METHODS: This study involved a systematic and independent review of relevant research articles published in reputable databases such as PubMed, Embase, Cochrane Library, and Web of Science. Two investigators conducted the review, which included studies published up to January 3, 2023. The quality of the eligible studies was evaluated and data were extracted using Review Manager software 5.4 (RevMan 5.4) to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The analysis comprised 35 studies and encompassed a collective sample of 18,246 individuals diagnosed with breast cancer. We did not find a statistically significant disparity in efficacy between conventional fractionated (CF) radiotherapy and hypofractionated (HF) radiotherapy regarding local recurrence (LR; OR = 0.91, 95% CI: 0.76-1.09, P = 0.30), disease-free survival (DFS; OR = 1.20, 95% CI: 1.01-1.42, P = 0.03), and overall survival (OS; OR = 1.08, 95% CI: 0.93-1.26, P = 0.28). Concerning safety, there was no significant difference between the HF and CF regimens in terms of breast pain, breast atrophy, lymphedema, pneumonia, pulmonary fibrosis, telangiectasia, and cardiotoxicity. However, the HF regimen resulted in lower skin toxicity (OR = 0.43, 95% CI: 0.33-0.55, P < 0.01) and improved patient fatigue outcomes (OR = 0.73, 95% CI: 0.60 - 0.88, P < 0.01). CONCLUSIONS: Although there is no substantial difference in LR, DFS, OS, or many other side effects between the HF and CF regimens, the HF regimen reduces skin toxicity and relieves patient fatigue. If these two issues need to be addressed in clinical situations, the HF regimen may be a superior alternative to conventional radiotherapy in postoperative breast cancer patients.

Extreme-hypofractionated RT with concomitant boost to the DIL in PCa: a 5-year update on oncological and patient-reported outcomes for the phase II trial "GIVE ME FIVE".

AIM: The present work reports updated oncological results and patients-reported outcomes at 5 years of phase II trial "Short-term high precision RT for early prostate cancer with SIB to the dominant intraprostatic lesion (DIL) for patients with early-stage PCa". METHODS: Data from patients enrolled within AIRC IG-13218 (NCT01913717) trial were analyzed. Clinical and GU/GI toxicity assessment and PSA measurements were performed every 3 months for at least 2 years after RT end. QoL of enrolled patients was assessed by IPSS, EORTC QLQ-C30, EORTC QLQ-PR25, and IIEF-5. Patients' score changes were calculated at the end of RT and at 1, 12, and 60 months after RT. RESULTS: A total of 65 patients were included. At a median follow-up of 5 years, OS resulted 86%. Biochemical and clinical progression-free survival at 5 years were 95%. The median PSA at baseline was 6.07 ng/ml, while at last follow-up resulted 0.25 ng/ml. IPSS showed a statistically significant variation in urinary function from baseline (p = 0.002), with the most relevant deterioration 1 month after RT, with a recovery toward baseline at 12 months (p ≤ 0.0001). A numerical improvement in QoL according to the EORTC QLQ-C30 has been reported although not statistically significant. No change in sexual activity was recorded after RT. CONCLUSIONS: The study confirms that extreme hypofractionation with a DIL boost is safe and effective, with no severe effects on the QoL. The increasing dose to the DIL does not worsen the RT toxicity, thus opening the possibility of an even more escalated treatment.

Optimized CAR-T therapy based on spatiotemporal changes and chemotactic mechanisms of MDSCs induced by hypofractionated radiotherapy.

Poor intratumoral infiltration is the major challenge for chimeric antigen receptor (CAR)-T cell therapy in solid tumors. Hypofractionated radiotherapy (HFRT) has been reported to induce immune cell infiltration and reshape the tumor immune microenvironment. Here, we showed that HFRT (5 × 5 Gy) mediated an early accumulation of intratumoral myeloid-derived suppressor cells (MDSCs) and decreased infiltration of T cells in the tumor microenvironment (TME) of immunocompetent mice bearing triple-negative breast cancer (TNBC) or colon cancer, which was further confirmed in tumors from patients. RNA sequencing (RNA-seq) and cytokine profiling analysis revealed that HFRT induced the activation and proliferation of tumor-infiltrated MDSCs, which was mediated by the interactions of multiple chemokines and chemokine receptors. Further investigation showed that when combined with HFRT, CXCR2 blockade significantly inhibited MDSCs trafficking to tumors and effectively enhanced the intratumoral infiltration and treatment efficacy of CAR-T cells. Our study demonstrates that MDSCs blockade combined with HFRT is promising for CAR-T cell therapy optimization in solid tumors.

[Stereotactic radiation therapy for liver tumours]. / Radiothérapie stéréotaxique hépatique.

Liver lesions are common in oncology, and various focal treatments can be used, such as surgery, chemoembolization, radiofrequency, and systemic treatment. However, these treatments are often not feasible for a number of reasons, including the patient's general health or the characteristics of the lesion itself. Additionally, localized relapses may occur after focal treatments. In the past, liver radiotherapy was limited by the toxicities it caused and was mainly used in palliative situations or specific pre-transplant management. However, advancements in high-precision radiotherapy, like hypofractionated radiotherapy in stereotactic conditions, have allowed to treat the lesions with minimal margins, delivering higher doses while reducing the healthy liver's exposure. Increasingly, retrospective and prospective studies have demonstrated the effectiveness and safety of hypofractionation for both primary and secondary liver lesions. This review discusses the indications, results, and techniques of this type of treatment.

Les lésions hépatiques primitives ou secondaires sont une situation fréquente en oncologie. Plusieurs types de traitements focaux peuvent être appliqués : chirurgie, chimio-embolisation, radio-fréquence, traitement systémique. Néanmoins, les traitements focaux sont régulièrement contre-indiqués, soit par l'état général et les antécédents du patient, soit par la lésion en elle-même (volume, situation). De plus, il peut y avoir des patients qui présentent des rechutes localisées après ce type de prise en charge. Le foie est un organe très radiosensible, et la radiothérapie hépatique a longtemps été limitée par les toxicités qu'elle engendrait. La radiothérapie est le plus souvent utilisée dans les situations très palliatives (irradiation hépatique en totalité) ou dans certains schémas de prise en charge avant greffe. Pourtant, l'avènement de la radiothérapie de haute précision, telle que la radiothérapie hypofractionnée en condition stéréotaxique, permet de traiter les lésions avec des marges minimes et donc, d'augmenter la dose délivrée en diminuant le volume de foie sain irradié. On retrouve aujourd'hui un nombre de plus en plus important de séries rétrospectives et prospectives qui décrivent son efficacité et sa tolérance tant pour les lésions primitives que secondaires. Nous faisons ici un point sur les indications, les résultats et les modalités de ce type de traitement.

Interleukin 8 in plasma is an efficacy marker for advanced non-small cell lung cancer treated with hypofractionated radiotherapy and PD-1 blockade.

BACKGROUND: Programmed death-1 (PD-1) blockade promotes combination therapy in advanced non-small cell lung cancer (NSCLC), hypofractionated radiotherapy (HFRT) and chemotherapy combined with immunotherapy improves the outcome of prognosis in advanced NSCLC, while effective biomarkers to follow prognostic efficacy are still to be found. METHODS: We enrolled 44 NSCLC patients with HFRT combined with PD-1 blockade, 13 patients with chemotherapy combined with immunotherapy, additionally collected tissue samples from 8 patients with earlystage NSCLC without therapy, and peripheral whole blood from 16 healthy donors, detected the expression differences of cytokines Interleukin 6 (IL-6), Interleukin 8 (IL-8) and Interleukin 17A (IL-17A) in the peripheral plasma and tissues by flow cytometry, immunofluorescence, and real-time fluorescence quantitative PCR. Cultured peripheral blood mononuclear cell (PBMC) and tumor-infiltrating T cells with recombinant human IL-8 in vitro to observe the changes of immune memory T cell subtypes and apoptosis. RESULTS: Our results show that IL-6, IL-8, and IL-17A are highly expressed in advanced NSCLC, high levels of IL-8 are significantly associated with poor prognosis in advanced NSCLC patients treated with HFRT + PD1 blockade, high circulating IL-8 in NSCLC increased apoptosis of effector memory RA (TemRA; CD45RA+CCR7-) T cell subsets and CD8+ T cell subsets in tissues, resulting in decreased peripheral TemRA and stem cell-like memory T cells (TSCM: CD45RA +CCR7 + CD95 +) in tissue. CONCLUSION: We suggest that IL-8 can impair immune memory function in NSCLC. It is a useful biomarker to evaluate the efficacy of HFRT + PD1 blockade in advanced NSCLC. Further exploration of easily available plasma biomarkers for personalized treatment of NSCLC is required.

Surgical resection versus transarterial chemoembolization followed by moderately hypofractionated radiotherapy in hepatocellular carcinoma.

BACKGROUND AND OBJECTIVE: Transarterial chemoembolization (TACE) is the gold standard treatment in intermediate hepatocellular carcinoma (HCC), but long-term disease control rates remain low. Herein, we compared results of TACE followed by hypofractionated radiotherapy (TACE-hRT) to surgical resection (SR) in early single or paucinodular intrahepatic HCC. METHODS: Between June 2004 and November 2016, data on 160 consecutive patients with Barcelona Clinic Liver Cancer (BCLC) stage A Child-Pugh A HCC treated with SR or TACE-hRT in our expert center were retrospectively reviewed. Time to progression (TTP), progression-free survival (PFS), and overall survival (OS) were evaluated. Clinical outcomes were compared using the stabilized-weights inverse probability of treatment weighting propensity score. RESULTS: Ninety-eight patients underwent SR and 62 were treated by TACE-hRT. Median total dose of RT was 54 Gy (interquartile range [IQR] 54-54) in 3­Gy fractions. Median OS follow-up was 93 months. TTP did not significantly differ between patients following SR and TACE-hRT, with 1­year rates of 68.2% and 82.6% (p = 0.17), respectively. In contrast, PFS and OS were lower in the TACE-hRT group (p = 0.015 and p = 0.006), with a median OS of 37 vs. 63 months for patients with surgery and TACE-hRT, respectively. In multivariate analysis, a significant negative impact on PFS and OS was seen for age at diagnosis, on TTP for alcohol-related liver disease, and on OS for total number of HCC nodules. Symptomatic grade ≥ 3 adverse events were presented by 42 (42.9%) SR and 19 (30.6%) TACE-hRT patients (p = 0.17). CONCLUSION: In patients presenting Child-Pugh A BCLC­A HCC with high risk for surgical complications, TACE-hRT can be an effective and safe treatment. However, surgical management remains the standard of care whenever possible.

Clinical outcomes of adapted hypofractionated radiotherapy for bladder cancer in elderly patients.

OBJECTIVE: To investigate the feasibility, efficacy, and safety of trimodal therapy (TMT) using a bifractionated split-course hypofractionated radiotherapy (RT) for non-metastatic muscle-invasive bladder cancer (MIBC) in elderly patients. PATIENTS AND METHODS: We retrospectively reviewed the characteristics and outcomes of patients aged >75 years with non-metastatic MIBC suitable or not for radical cystectomy (RC) and treated with transurethral resection of bladder tumour followed by concomitant radio-chemotherapy (platinum salt and 5-fluorouracil) at two institutions (Saint Louis Hospital, Paris, France and European Georges Pompidou Hospital, Paris, France) between 1990 and 2021. RT consisted of an adapted bifractionated split-course hypofractionated RT. Acute toxicities were reported according to Common Terminology Criteria for Adverse Events version 5.0 and late toxicities were reported according to the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer late radiation morbidity scoring schema. The primary end-point was overall survival (OS). Secondary end-points included other survivals outcomes and safety. RESULTS: A total of 122 patients were identified, with a median (range) follow-up of 51.1 (0.5-210.8) months. In all, 83.5% of patients completed radio-chemotherapy. The OS rate was 61.7% at 3 years and 51.2% at 5 years. In multivariate analysis, the completion of RT and concomitant chemotherapy were significantly associated with better OS and cancer-specific survival. For patients fit for RC, a complete histological response was achieved for 77 patients (91.7%) with radio-chemotherapy and the bladder conservation rate was 90.5%. Acute and late Grade ≥3 toxicities were <5%. CONCLUSION: Bifractionated split-course hypofractionated RT with concomitant chemotherapy regimen appears to be well-tolerated and effective. Trimodal treatment seems to be a curative option for elderly patients unfit for radical surgery compared with palliative care and may contribute to improved survival in these patients.

A Precise Approach for Radiotherapy of Breast Cancer.

Radiotherapy is an integral part of the multidisciplinary management of breast cancer (BC). There have been multiple recent advances in the delivery of radiotherapy, reviewed with a critical discussion of the evidence from trials investigating adjuvant ultra-hypofractionation and partial breast irradiation for early-stage BC, and the locoregional management of lymph nodes in locally advanced BC. Multiple precision medicine-based approaches have been developed as prognostic and/or predictive for BC patients and identifying biomarkers of radioresistance could help identify patients that may benefit from dose-escalated radiotherapy or radiosensitizers. Radiotherapy after breast reconstruction is an area of current controversy in the field, and we evaluated the decision-making considerations in this situation. The oligometastatic state is an emerging field for many cancer sites based on recent trials investigating ablative radiotherapy for oligometastatic BC. This chapter is an overview of radiotherapy for BC, with a focus on recent advances in early-stage, locally advanced, and oligometastatic disease.

The impact of short-course hypofractionated radiotherapy on multimodality treatment utilisation, compliance, and outcome in glioblastoma patients: a Danish patterns of care study.

BACKGROUND: The aim of this retrospective registry-based Danish patterns of care study was (1) to evaluate the real-world utilisation of short-course hypofractionated radiotherapy (HFRT) in glioblastoma (GBM) patients over time, and (2) to evaluate the impact of short-course HFRT by assessing trends in multimodality treatment utilisation, compliance, and outcome. MATERIAL AND METHODS: Data of all adults with newly diagnosed pathology-confirmed GBM between 2011 and 2019 were extracted from the nationwide Danish Neuro-Oncology Registry. Short-course HFRT was defined as a fraction size of > 2 Gy to a planned dose of > 30 Gy. Patterns of care were assessed. To analyse trends in the assignment to short-course HFRT, and in radiotherapy (RT) compliance, multivariable logistic regression was applied. To analyse trends in survival, multivariable Cox regression was used. RESULTS: In this cohort of 2416 GBM patients, the utilisation of short-course HFRT significantly increased from ca. 10% in 2011 to 33% in recent years. This coincided with the discontinued use of palliative regimens and a decreased use of conventional fractionation. The proportion of patients proceeding to RT remained stable at ca. 85%. The proportion of patients assigned to chemoradiotherapy (CRT) remained stable at ca. 60%; the use of short-course hypofractionated CRT increased with ca. 10%, while the use of conventionally fractionated CRT decreased with ca. 10%. Compliance with conventionally fractionated and short-course HFRT was respective 92% and 93%, and significantly increasing in recent years. In the complete cohort, the median overall survival remained stable at ca. 11 months. Assignment to short-course HFRT was independently associated with shorter survival. CONCLUSION: In Denmark, the use of short-course HFRT significantly increased in recent years. Nonetheless, the overall utilisation of RT and chemotherapy did not increase on a population level. Nor did survival change. In contrast, compliance with both conventionally fractionated RT and short-course HFRT increased.

Accelerated hypofractionated radiotherapy with 3 Gy per fraction for central/ultra-central lung tumors: toxicity to mediastinal organs.

BACKGROUND: Accelerated hypofractionated radiotherapy with 3 Gy per fraction is routinely performed for central lung tumors in Japan. However, the tolerable doses to mediastinal organs at risk during this procedure are unclear. This study aimed to clarify the rate of toxicities and tolerable doses to mediastinal organs. METHODS: Patients treated with accelerated hypofractionated radiotherapy using a total dose of 60-75 Gy, with 3 Gy per fraction, for central lung tumors (July 2009-April 2021) were retrospectively reviewed. We extracted patients who received ≥30 Gy irradiation to each mediastinal organ and analyzed dosimetric factors, including doses to 0.03, 0.5, 1, 4 and 10 mL of each organ, in relation to grade 3-5 toxicities, except for radiation pneumonitis. RESULTS: In total, 251 organs in 91 (ultra-central, 24) lesions were analyzed, with a median follow-up duration of 26 months (range, 4-94). The prescribed doses were 75/72/69/66/63/60 Gy for 52/14/16/3/2/4 lesions, respectively. Grade 3 bronchopulmonary hemorrhage was confirmed in two (2.2%) patients, whose tumors were located ultra-centrally. The two patients with toxicity received up to 74.5 and 71.6 Gy to the bronchus. Among patients who received 70 Gy or more to the bronchus, the incidence rate was 7% (2/28 patients). CONCLUSION: The rate of severe toxicities was low (2.2%). Although we did not identify the dose tolerance of the organs, because of the low incidence rate, we did note that doses of >70 Gy to the bronchus were likely to cause bronchopulmonary hemorrhage.

Dose-escalation by hypofractionated simultaneous integrated boost IMRT in unresectable stage III non-small-cell lung cancer.

BACKGROUND: To explore the maximum tolerated dose (MTD) and evaluate the safety of dose escalation using hypofractionated simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) concurrent with chemotherapy for unresectable stage III non-small cell lung cancer (NSCLC). METHODS: Four escalating radiation dose levels were used. This study included 25 patients with previously untreated NSCLC who received six concurrent weekly chemotherapy cycles comprising cisplatin and docetaxel. Dose-limiting toxicity (DLT) was defined as any acute toxicity that interrupted radiotherapy for more than 1 week. MTD was defined as the highest dose level that didn't induce DLT or grade 5 toxicity in two patients. RESULTS: All 25 patients received the prescribed escalating radiation dose from the start dose up to LEVEL 4. Two patients experienced DLT at dose LEVEL 4. One patient died because of upper gastrointestinal hemorrhage within 6 months after radiotherapy, whereas another patient among the additional five patients died because of grade 5 radiation pneumonitis within 2 months after radiotherapy. Dose LEVEL 3 was defined as MTD. The 1- and 2-year local controls were 82.8 and 67.8%, respectively. The median progression-free survival was 15.4 months, whereas the median overall survival was 27.3 months. CONCLUSIONS: Dose escalation was safely achieved up to LEVEL 3 [the planning gross target volume (PTVG) 60.5 Gy/22 Fx, 2.75 Gy/Fx; the planning clinical target volume (PTVC) 49.5 Gy/22 Fx] using SIB-IMRT concurrently with chemotherapy for unresectable stage III NSCLC, and the acute toxicities were generally well tolerated. Further prospective studies on long-term outcomes and late toxicities are warranted. TRIAL REGISTRATION: Retrospective registration, ChiCTR1900027290 (08/11/2019).

Improved Oxygenation of Human Skin, Subcutis and Superficial Cancers Upon Mild Hyperthermia Delivered by WIRA-Irradiation.

Clinical trials have shown that mild hyperthermia (HT) serves as an adjunct to cancer treatments such as chemo- and radiotherapy. Recently, a high efficacy of mild HT immediately followed by hypofractionated radiotherapy (RT) in treatment of recurrent breast cancer has been documented if temperatures of 39-43 °C are achieved for 40-60 min. In the present study, temperature and oxygenation profiles were measured in superficial tissues of healthy volunteers exposed to water-filtered infrared-A- (wIRA)- irradiation, to verify that adequate thermal doses together with the improved tumor oxygenation necessary for radiosensitisation are obtained. Experiments were performed using a wIRA-system equipped with two wIRA-radiators, each with a thermography camera for real-time monitoring of the skin surface temperature. Temperatures within the abdominal wall were measured with fibre optic sensors at defined tissue depths (subepidermal, and 1-20 mm inside the tissue). The corresponding tissue pO2 values were assessed with fluorometric microsensors. In selected situations, hyperspectral tissue imaging was used to visualise the oxygenation status of normal skin and superficial tumours in patients. Pre-treatment skin surface temperature was 34.6 °C. Upon wIRA exposure, average skin surface temperatures reached 41.6 °C within 5-12 min. Maximum tissue temperatures of 41.8 °C were found at a tissue depth of 1 mm, with a steady decline in deeper tissue layers (41.6 °C @ 5 mm, 40.8 °C @ 10 mm, 40.6 °C @ 15 mm, and 40.1 °C @ 20 mm). Effective HT levels ≥39 °C were established in tissue depths up to 25 mm. Tissue heating was accompanied by a significant increase in tissue pO2 values [e.g., at a tissue depth of 13 mm mean pO2 rose from 46 mmHg to 81 mmHg (@ T = 40.5 °C). In the post-heating phase (+ 5 min), pO2 was 79 mmHg (@ T = 38 °C) and 15 min post-heat pO2 was 72 mmHg (@ T = 36.8 °C)]. pO2 values remained elevated for 30-60 min post-heat. Non-invasive monitoring of normal skin and of recurrent breast cancers confirmed the improved O2 status by wIRA-HT. In conclusion, wIRA-irradiation enables effective tissue heating (T = 39-43 °C) associated with distinct increases in blood flow and pO2. These adjustments unequivocally meet the requirement for effective radiosensitisation.

Ultra-Hypofractionated vs. Moderate Fractionated Whole Breast Three Dimensional Conformal Radiotherapy during the COVID-19 Pandemic.

Background and Objectives: Reducing time of treatment during COVID-19 outbreaks has been recommended by the leading Radiation Oncology societies. Still minimizing radiation induced tissue toxicity is one of the most important issues in breast cancer patients. The study aimed to investigate compliance, clinical and dosimetry normal tissue toxicity, and cosmetic results between moderated and ultra-fractionated regimes for breast cancer patients during COVID-19 pandemic. Materials and Methods: This pilot prospective randomized study included 60 patients with early breast cancer after preserving surgery, 27 patients advocated to ultra-hypofractionated whole-breast three dimensional (3D) conformal radiotherapy of 26 Gy in 5 fractions over 1 week and 33 patients with moderate fractionated breast 3D conformal radiotherapy patients between March 2020 and July 2020, during the COVID pandemic outbreak. The compliance to treatment, dosimetric parameters, acute and late skin toxicity, subcutaneous tissue toxicity, cosmetic results and clinical follow up for 18 months for the two regimes were analyzed and compared. Results: When two regimes were compared 5 fraction group had significantly lower prevalence of newly infected cases of SARS-CoV-2 and thus delayed/interrupted treatment (p = 0.05), comparable grade 1 CTCAE v5, acute skin toxicity (p = 0.18), Grade 1 Radiation Morbidity Scoring Scheme (RESS) subcutaneous tissue toxicity (p = 0.18), Grade 1 RESS late skin toxicity (p = 0.88) and cosmetic results (p = 0.46). Dosimetric results reveled that patients in 5 fraction group received significantly lower median ipsilateral lung doses (p < 0.01) in addition to left breast cancer patients that received significantly lower median heart dose (p < 0.01) and median left anterior descending artery (LAD) dose (p < 0.01). Conclusion: Ultra-hypofractionated radiotherapy for breast cancer is comparable to moderate hypofractionation regimen regarding grade 1 acute skin toxicity, grade 1 subcutaneous tissue toxicity, late skin toxicity and cosmetic results. Application of ultra-hypofractionated radiotherapy with significantly lower radiation doses for lung and heart could be crucial in reducing the risk of acute/late pulmonary and heart radiation-induced toxicity.

Hypofractionated radiotherapy for renal cell carcinoma with inferior vena cava tumour thrombus.

Renal cell carcinoma (RCC) constitutes about 3% of all malignant neoplasms in adults. Clear cell carcinoma is the most frequent type, accounting for about 65% of cases. It tends to invade the veins and form tumour thrombi in inferior vena cava (IVC-TT), occasionally reaching the right atrium. Nephrectomy and thrombectomy are standard therapeutic procedures performed in RCC-IVC-TT. Despite proven effectiveness of surgery, this entity in IVC-TT is associated with poor outcome. The role of palliative radiotherapy in this entity is undetermined. We present a case of a 43-year-old female patient after right-sided nephrectomy due to advanced RCC which invaded the IVC, hepatic veins, and right atrium. The patient has been treated with postoperative, hypofractionated radiotherapy on the residual disease.

Hypofractionation as a solution to radiotherapy access in latin america: expert perspective.

Background: Limited radiation therapy resources have resulted in an interest in developing time and cost-saving innovations to expand access to cancer treatment, in Latin America. Therefore, hypofractionated radiotherapy (HRT) is a possible solution, as this modality delivers radiation over a shorter period of time. Materials and methods: A selected panel of Latin American (LA) experts in fields related to HRT were provided with a series of relevant questions to address, prior to the multi-day conference. Within this meeting, each narrative was discussed and edited, through numerous rounds of discussion, until agreement was achieved. Results: The challenges identified in increasing the adoption of HRT in LA include a lack of national and regional clinical practice guidelines and cancer registries; a lack of qualified human resources and personnel education; high up-front costs of equipment; disparate resource distribution and scarce HRT research. An analysis for these overarching challenges was developed and answered with recommendations. Conclusion: Extending the adoption of HRT in LA can provide a path forward to increase access to radiotherapy and overcome the shortage of equipment. HRT has the potential to improve population health outcomes and patient centered care, while offering comparable local control, toxicity, palliation, and late effects for multiple indications, when compared to conventional RT. Concerted efforts from all involved stakeholders are needed to overcome the barriers in adopting this strategy in LA countries. The recommendations presented in this article can serve as a plan of action for HRT adoption in other countries in a similar situation.

Hypofractionated volumetric-modulated arc therapy for breast cancer: A propensity-score-weighted comparison of radiation-related toxicity.

We assessed the clinical benefit of combining volumetric-modulated arc therapy (VMAT) and hypofractionated radiotherapy (HF-RT) considering the incidence of radiation-related toxicities. After a retrospective review for breast cancer patients treated with adjuvant RT between 2005 and 2017, a total of 4209 patients treated with three-dimensional conventional fractionation (CF-3D, 50.4 Gy/28 fractions) and 1540 patients treated with HF-RT (768 received HF-3D; 772, HF-VMAT; 40 Gy/15 fractions) were included. A total of 2229 patients (38.8%) received regional node irradiation (RNI): 1642 (39.0%), 167 (21.7%) and 420 (54.4%) received RNI via CF-3D, HF-3D and HF-VMAT, respectively. Acute/subacute and late toxicities were evaluated. Propensity scores were calculated via logistic regression. Grade 2+ acute/subacute toxicities was the highest in CF-3D group (15.0%, 2.6% and 1.6% in CF-3D, HF-3D and HF-VMAT, respectively; P < .001). HF-VMAT reduced Grade 2+ acute/subacute toxicities significantly compared to CF-3D (odds ratio [OR] 0.11, P < .001) and HF-3D (OR 0.45, P = .010). The 3-year cumulative rate of late toxicities was 18.0% (20.1%, 10.9% and 13.4% in CF-3D, HF-3D and HF-VMAT, respectively; P < .001). On sensitivity analysis, the benefit of HF-VMAT was high in the RNI group. Acute and late toxicities were fewer after HF-VMAT than after HF-3D or CF-3D, especially in women who underwent RNI.

A hesitated approach: primary radiotherapy for keloids-a case series.

PURPOSE: To assess the efficacy and toxicity of hypofractionated radiotherapy (RT) alone in treatment-resistant symptomatic keloids. METHODS: Six patients with a total of 13 inoperable large keloid lesions and no response to previous treatments were admitted to our department between 2017 and 2019. All patients were examined for detailed wound localization, size, contour, and color assessment, and for objective and subjective symptoms. Response to treatment was graded as "complete remission" in case of full symptomatic relief and >75% decrease in lesion size, as "partial remission" in case of partial symptomatic relief and 25-75% decrease in lesion size, and as "stable disease" in case of no symptomatic relief or <25% decrease in lesion size. Patients were followed up monthly for the first 3 months and every 3 months thereafter by physical examination. RESULTS: A total dose of 37.5 Gy external RT in five fractions was prescribed by 6­MeV electrons in 4 patients and 6­MV photons in 2 patients. Complete response was obtained in all patients at the 6­month control. All patients were satisfied with cosmetic results at their last control. Grade 2 dermatitis developed in all patients during the second week of RT but resolved completely in all after 6 months following the end of RT. CONCLUSION: In keloids that are unresponsive to standard treatment, hypofractionated RT using a total dose of 37.5 Gy in five fractions is feasible.

Hypofractionated radiotherapy in ten fractions for postmastectomy patients: a phase II study compared with another hypofractionation schedule with sixteen fractions.

BACKGROUND: The purpose of this phase II study was to evaluate the feasibility of hypofractionated radiotherapy (HFRT) with a dose of 36.5 Gy in 10 fractions in postmastectomy patients. METHODS: From March 2014 to December 2015, 85 patients with locally advanced breast cancer were eligible to participate in this study with a schedule of 36.5 Gy in 10 fractions. Intensity-modulated radiation therapy (IMRT) was delivered to the chest wall with or without the supraclavicular region. The primary endpoint was radiation-related toxicities. The secondary endpoints were locoregional failure-free survival (LRFFS), disease-free survival (DFS) and overall survival (OS). And the outcomes were compared with our retrospective study of 72 patients with 42.5 Gy in 16 fractions. RESULTS: The median follow-up was 69.0 (range 66.5-71.5) months in the 36.5 Gy group and 93.0 (range 91.9-94.1) months in the 42.5 Gy group, respectively. Radiation-related toxicities were mainly grade 1, although a few patients had grade 2 plexopathy (1.2%) and acute skin toxicity (1.2%) in the 36.5 Gy group, and grade 2 acute skin toxicity (5.6%) and lymphedema (4.2%) in the 42.5 Gy group. There were no significant differences between the groups in acute and late toxicities. For all the patients, the 5-year LRFFS, DFS and OS were 97.7 and 100.0%, 93.1 and 90.3%, 98.8 and 97.2%, respectively, without significant differences between the groups. CONCLUSION: Postmastectomy HFRT with a schedule of 36.5 Gy in 10 fractions was feasible, with mild toxicities and excellent 5-year clinical outcome. TRIAL REGISTRATION: Trial registration number: ChiCTR-ONRC-14004391 . Date of registration: 9/3/2014.