Hypofractionated Radiotherapy Regimen Research Articles

Weekly ultra-hypofractionated radiotherapy in localised prostate cancer

BackgroundModerately hypofractionated radiotherapy regimens or stereotactic body radiotherapy (SBRT) are standard of care for localised prostate cancer. However, some patients are unable or unwilling to travel daily to the radiotherapy department and do not have access to, or are not candidates for, SBRT. For many years, The Royal Marsden Hospital NHS Foundation Trust has offered a weekly ultra-hypofractionated radiotherapy regimen to the prostate (36 Gy in 6 weekly fractions) to patients unable/unwilling to travel daily. MethodsThe current study is a retrospective analysis of all patients with non-metastatic localised prostate cancer receiving this treatment schedule from 2010 to 2015. ResultsA total of 140 patients were included in the analysis, of whom 86 % presented with high risk disease, with 31 % having Gleason Grade Group 4 or 5 disease and 48 % T3 disease or higher. All patients received hormone treatment, and there was often a long interval between start of hormone treatment and start of radiotherapy (median of 11 months), with 34 % of all patients having progressed to non-metastatic castrate-resistant disease prior to start of radiotherapy. Median follow-up was 52 months. Median progression-free survival (PFS) and overall survival (OS) for the whole group was 70 months and 72 months, respectively. PFS and OS in patients with hormone-sensitive disease at time of radiotherapy was not reached and 75 months, respectively; and in patients with castrate-resistant disease at time of radiotherapy it was 20 months and 61 months, respectively. ConclusionOur data shows that a weekly ultra-hypofractionated radiotherapy regimen for prostate cancer could be an option in those patients for whom daily treatment or SBRT is not an option.

Management of malignant superior vena cava syndrome.

Superior vena cava (SVC) syndrome occurs due to obstructed blood flow through the SVC. It can present clinically on a spectrum, between asymptomatic and life-threatening emergency. Patients commonly report a feeling of fullness in the head, facial, neck and upper extremity edema, and dyspnea. On imaging, patients commonly have superior mediastinal widening and pleural effusion. The majority of cases are due to malignant causes, with non-small cell lung cancer, small cell lung cancer, and lymphoma the most commonly associated malignancies. When evaluating patients, a complete staging workup is recommended, as it will determine whether treatment should be definitive/curative or palliative in intent. If the patient requires urgent treatment of venous obstruction, such as in the cases of acute central airway obstruction, severe laryngeal edema and/or coma from cerebral edema, direct opening of the occlusion by endovascular stenting and angioplasty with thrombolysis should be considered. Such an approach can provide immediate relief of symptoms before cancer-specific therapies are initiated. The intent of treatment is to manage the underlying disease while palliating symptoms. Treatment approaches most commonly employ chemotherapy and/or radiation therapy depending on the primary histology. Mildly hypofractionated radiation regimens are most commonly employed and achieve high rates of symptomatic responses generally within 2 weeks of initiating therapy.

Hypofractionated radiotherapy for glioblastoma: A large institutional retrospective assessment of 2 approaches.

Glioblastoma (GBM) poses therapeutic challenges due to its aggressive nature, particularly for patients with poor functional status and/or advanced disease. Hypofractionated radiotherapy (RT) regimens have demonstrated comparable disease outcomes for this population while allowing treatment to be completed more quickly. Here, we report our institutional outcomes of patients treated with 2 hypofractionated RT regimens: 40 Gy/15fx (3w-RT) and 50 Gy/20fx (4w-RT). A single-institution retrospective analysis was conducted of 127 GBM patients who underwent 3w-RT or 4w-RT. Patient characteristics, treatment regimens, and outcomes were analyzed. Univariate and multivariable Cox regression models were used to estimate progression-free survival (PFS) and overall survival (OS). The impact of chemotherapy and RT schedule was explored through subgroup analyses. Median OS for the entire cohort was 7.7 months. There were no significant differences in PFS or OS between 3w-RT and 4w-RT groups overall. Receipt and timing of temozolomide (TMZ) emerged as the variable most strongly associated with survival, with patients receiving adjuvant-only or concurrent and adjuvant TMZ having significantly improved PFS and OS (P < .001). In a subgroup analysis of patients that did not receive TMZ, patients in the 4w-RT group demonstrated a trend toward improved OS as compared to the 3w-RT group (P = .12). This study demonstrates comparable survival outcomes between 3w-RT and 4w-RT regimens in GBM patients. Receipt and timing of TMZ were strongly associated with survival outcomes. The potential benefit of dose-escalated hypofractionation for patients not receiving chemotherapy warrants further investigation and emphasizes the importance of personalized treatment approaches.

Radiotherapy in Extramammary Paget’s disease: It’s worth it? A Case Report and Literature Review

Extramammary Paget’s disease (EMPD) is a rare and heterogeneous clinical picture usually recorded on apocrine gland-bearing epidermis areas in extramammary sites, showing a potential invasive evolution and poor prognosis. At diagnosis, it could appear as a primary tumor with secondary co-exhisting visceral malignancies like in anus, male or female genital system, which should be assessed. This rare epidermal carcinoma generally occurs in individuals older than 60 years mainly in Caucasian female and Asian male ethnicity. Although the pathophisiology has been well established, its management is still controversial and requires a multidisciplinary team approach. There are several therapeutic strategies. Among them, radiotherapy is accounted as an effective option in primary or in adjuvant timing but up to now no definitive role has been assessed. Data by case series, case reports and retrospective analyses have provided results on the positive benefit of HDR brachytherapy or external beam radiotherapy (EBRT) mainly in very old patients not suitable for extended surgery, which remains the main treatment care. Long course radiotherapy is a big concern in elderly patients due to logistics and care assistance deficiencies, which makes their access difficult to the radiation centres. Thus, hypofractionated radiotherapy regimens could be a good compromise problem solving to provide excellent local control within a short treatment time. Herein, we present a case of EMPD occurring in a 80 years old woman with vulvo-perineal extension successfully treated with hypofractionated external beam radiotherapy as primary treatment using a schedule 300cGy/fr/51 Gy in 17 treatment days.

Factors affecting the survival of patients with glioblastoma treated with standard and hypofractionated radiation regimens

Background. Glioblastoma has the worst prognosis and is the most common primary tumor of the central nervous system (CNS) among adults. Since it is multimodal treatment that increases survival chances of patients with glioblastoma, the analysis of factors that affect survival is a necessary precondition for developing more effective therapeutic approaches for this cohort. Such analysis makes it possible to determine the subgroups of patients which demonstrate the biggest therapeutic benefit from certain types of multimodal treatment, thus leading to implementation of personalized neuro-oncological treatment. Purpose. To analyze factors affecting cancer-specific survival (CSS) of patients with glioblastoma in stratification of the cohort according to the regimen of adjuvant radiation therapy into groups of standard and hypofractionated treatment regimens. Materials and methods. The single-center non-randomized study is based on the analysis of the results of the cohort of 159 patients with primarily diagnosed glioblastoma that were treated over the period from 2014 to 2020 at the State Institution «Romodanov Neurosurgery Institute of the National Academy of Medical Sciences of Ukraine». According to the regimen of radiation therapy, the patients of the cohort (n=159) were stratified into two groups: standard regimen group – 49 (30.8%) patients (30 fractions, total radiation dose of 60.0 Gy) and hypofractionated regimen group – 110 (69.2%) patients (15 fractions, total radiation dose of 52.5 Gy). The survival of the patients was analyzed by the Kaplan–Meier method. The log-rank test was used for comparing Kaplan–Meier survival curves for different studied groups. For the purpose of studying impact of independent variables on the survival, we used regression analysis according to semiparametric proportional hazards model. Hazard ratio was calculated with 95% confidence intervals (CI). Results and discussion. The median CSS in the total cohort was 16.6 (95% CI 14.1–17.8 months) months in median follow-up time of 23.8 (95% CI 21.9–27.3) months. In standard regimen group, the median CSS was 15.7 (95% CI 14.1–17.8) months in median follow-up time of 24.4 (95% CI 23.1–25.3) months. In hypofractionated regimen group, the median CSS was 17.5 (95% CI 14.6–19.7) months in median follow-up time of 22.3 (95% CI 21.3 – 27.2) months. According to the logrank test (taking into consideration cautions about its use), no statistically significant difference in CSS of patients of both groups was determined р=0.07&gt;0.05. For analysis of the impact of clinical factors (age, sex, radicality of the surgical treatment, chemotherapeutic treatment, functional status according to the Karnofsky scale) on the CSS of both groups, they were considered as the ones that may have different base hazard. Statistically significant impact of all studied covariates on the CSS was registered (p70 points, ceteris paribus. For male patients, the hazard of death is 1.7 times higher (р=0.016267; HR 1.7; 95% CI 1.1–2.5) than for female patients, ceteris paribus. Absence of chemotherapy in adjuvant treatment increases hazard of death by 2.37 times (HR 2.37; 95% CI 1.6–3.2), ceteris paribus. The hazard of death decreases, ceteris paribus, by 82% in chemotherapy with temozolomide and by 47% when the patient is younger than 60 years old (HR 0.53; 95% CI 0.4–0.8). Conclusions. This analysis is a stage of the study of differentiated treatment effect in groups of standard and hypofractionated regimens of radiation therapy in patients with glioblastoma. These data can be used for an in-depth subgroup analysis and serve as the basis for development of personalized approaches in treatment of neuro-oncological patients.

Hypofractionated Radiotherapy for Hematological Malignancies during COVID-19 Pandemic and Beyond.

Conventionally fractionated radiotherapy (RT) has shown to have excellent local control in hematological malignancies (HM). Up to date there is none or scant literature about the use of hypofractionated radiotherapy (HFRT) for the treatment of HM, this single institution study analyzed the efficacy of HFRT in HM. We hypothesized that HFRT in HM will result in a similar local tumor control that has been reported with standard fractionated RT. In this retrospective study, we analyzed the data from patients within the provincial cancer registry diagnosed with HM treated with a curative intent using HFRT regimens suggested by International Lymphoma Radiation Oncology Group between 2020-2022 during the COVID-19 pandemic. Primary outcome of the study was overall response rate (ORR), measured as complete response (CR), partial response (PR) or stable disease (SD) within the irradiated field determined radiologically or clinically post completion of RT. Secondary end point was freedom from local progression (FFLP), calculated from the date of initiation of RT to the first date among in-field progression, death, and last follow-up. Summary statistics were used to describe cohort and treatment characteristics. FFLP was calculated by 1 minus cumulative incidence accounting for competing risk (i.e., death). Of the 36 patients included for analysis, 18 were aggressive non-Hodgkin lymphoma (NHL), 9 were indolent NHL, 6 were Hodgkin lymphoma (HL) and 3 were other HM. Among them 25 had consolidation RT and 11 had definitive RT. HFRT daily dose per fraction ranged from 2.67 Gy to 5 Gy and total dose regimens ranged from 18 Gy to 42.5 Gy in 6 - 17 fractions and median equivalent dose in 2 Gy fractions (EQD2) for alpha/beta = 10Gy was 36 Gy (±7.5). ORR for the entire cohort was 94.4%. With a median follow up of 13.2 months, FFLP at one year for the entire cohort was 91.5% and death without infield progression was 8.7%. Among the 4 patients who had in radiation field recurrence, 2 had aggressive NHL and 2 had HL. No grade 3 or 4 acute toxicities were reported. This retrospective study using HFRT showed an ORR and FFLP comparable to historical studies using standard fractionation. Further long-term follow-up is warranted to confirm these findings.

Hypofractionated Accelerated Radiation Dose-Painting (HARD) vs. Standard Radiotherapy for Unresected Soft-Tissue Sarcoma

Conventionally fractionated radiotherapy (CFRT) offers modest local control (LC) for unresected soft tissue sarcoma (STS). Although STS has a low α/β (∼2 - 6) that may benefit from a hypofractionated radiotherapy regimen, it is often limited due to the toxicity risk to surrounding organs. A simultaneous integrated boost to gross disease (2.5 - 3 Gy/fraction), with lower doses to the intermediate and low risk target volume, may offer a safe isotoxic dose escalation approach. We hypothesize that this hypofractionated accelerated radiotherapy dose-painting (HARD) will improve local control compared to CFRT. We performed a single institution retrospective analysis of patients who received external beam radiotherapy with definitive intent (≥50 Gy) for unresected STS. CFRT was defined as 1.8 - 2 Gy/fraction (Gy/fx). HARD regimens consisted of 60 - 66 Gy at 3 Gy/fx or 70 Gy at 2.5 Gy/fx to gross disease, with 1.8 - 2.4 Gy/fx to intermediate and low risk regions. All anatomical sites and histologies were included. Local control (LC) was defined from date of current diagnosis, estimated by Kaplan-Meier methods via log-rank tests or Cox regression for univariate analysis (UVA), when appropriate. Cox regression multivariate analysis (MVA) included regimen, biological effective dose (α/β 6; BED6), lesion size, age, and grade. We identified 77 patients with primary and metastatic STS treated with HARD (n = 40) or CFRT (n = 37) between 1990 and 2022, with a median follow up of 24 months in surviving patients. The mean dose for CFRT and HARD are 56.8 Gy (50 - 77.4 Gy) and 64.9 Gy (60 - 70 Gy), respectively. HARD was comprised of 65% for 3 Gy/fx and 35% for 2.5 Gy/fx regimens. At the time of RT, grade 3 (69%) and extremity (39%) tumors were the most common. Tumor histology was very heterogenous across both cohorts, with undifferentiated pleomorphic sarcoma being the most common for HARD (33%) and CFRT (19%). HARD was more often utilized in stage IV patients (55% vs. 19%, p = 0.001) and had a higher mean BED6 (96 vs. 74.2 Gy, p < 0.001) than CFRT, but without differences in age (67 vs. 59 years), tumor size (8 vs. 10 cm), concurrent chemotherapy (35% vs. 30%), Karnofsky performance status (86 vs. 85), follow-up (19 vs. 28 months), and grade (all p > 0.1). On UVA, there was a LC benefit associated with higher BED6 (HR 0.94, 95% CI 0.9 - 0.98, p = 0.002) and the HARD regimen (2-year LC 95% vs. 62%, p < 0.001). On MVA, only HARD (HR 0.07, 95% CI 0.006 - 0.729, p = 0.027) was independently associated with LC. Although the HARD regimen and higher BED6 were both associated with significant improvement in LC, only the HARD regimen independently associated with a local control benefit for unresected STS. These results suggest biologic dose-intensification exploiting the low α/β of STS with an isotoxic hypofractionated regimen may be a favorable strategy for unresectable STS. Future prospective studies are necessary to validate these findings.

5-Year Results from a Prospective Phase II Trial of Ten-Fractions Hypofractionated Radiotherapy in Locally Advanced Breast Cancer

There is a growing interest for adjuvant loco-regional hypofractionated radiotherapy (Hypo-RT) regimens in patients (pts) undergoing surgery for locally advanced breast cancer (LABC). We report the 5-year results of a phase II study on Hypo-RT targeting the primary and regional lymph nodes in ten fractions (fxs). A schedule of 34 Gy/10 fxs/2 wks to the whole breast/chest wall and to the draining lymph nodes was used; an optional single fraction 8 Gy boost was administered with electrons to the tumor bed in patients who had undergone conservative surgery. Both acute (CTCAE 4.0) and late (LENT/SOMA) toxicities were collected. All pts but those who underwent mastectomy without reconstruction or with temporary expander were also asked to rate their cosmetic outcome according to the Harvard scale. Toxicity was assessed weekly during RT and then at each follow-up (fup) examination (1, 3, 6 months and then yearly). Late toxicity was assessed starting from 3 months after the end of Hypo-RT and loco-regional toxicity was prospectively collected. Cancer related endpoints in terms of loco-regional (LR) recurrence, distant metastasis, specific disease- free survival and overall survival (OS) were evaluated from the date of RT start to the diagnosis of local relapse/distant metastases or the last fup respectively. From February 2015 to March 2019, 59 women (median age 60 yrs, IQR: 48.3-68.8 yrs) with stage II to IIIA breast cancer who underwent axillary dissection and conservative surgery (83%) or mastectomy (17%) were accrued. One patient was lost to fup immediately after the end of RT. Of the 58 evaluable pts, 56 underwent neo-adjuvant (27.5%) or adjuvant (57%) chemotherapy and 15.5% exclusive hormone therapy as well. Trastuzumab was administered concomitant to RT in HER2 positive pts (25%). All pts completed treatment as planned. No grade 2+ acute toxicity was recorded. At the median fup of 63 months (range: 25-92 mths), the cumulative incidence of any grade locoregional late toxicity estimated with the Kaplan-Meier method is 43.4% (95% CI) (30.0% and 46.1% for patients undergone mastectomy and lumpectomy, respectively). Peak 2 events have been observed for fibrosis (1 pt, 1.7%), telangiectasia (1 pts, 1.7%) and lymphoedema (1 pt, 1.7%). One patient (1.7%) experienced grade 3 breast retraction. Of all eligible patients (N = 51), patient reported cosmetic outcome was excellent, good, fair and poor in 51.7%, 22.4%, 10.3% and 3.4%, respectively. No late lung toxicity was observed. The actuarial LR control rate at 5 years is 98%; for distant metastasis-free survival, specific disease-free survival and OS rates are 89.2%, 80.8% and 93.7% respectively. Our results support the activity of a 10-fxs Hypo-RT schedule targeting the primary site as well as the draining lymph node stations after surgery for LABC.

Hypo-Fractionated Palliative QUADSHOT Radiotherapy and Concurrent CDDP in Patients with LAHNSCC: Toxicities and Clinical Outcomes

Shorter palliative hypo-fractionated radiotherapy regimens given concurrently with chemotherapy, preferably cisplatin (radiosensitizer), increase response rates with acceptable toxicity, leading to better compliance of patients with locally advanced squamous cell carcinoma of the head and neck (LAHNSCC) in whom late toxicities due to chemoradiotherapy are less relevant. This single institution prospective interventional phase II study was conducted with the goal of achieving high rates of locoregional control with acceptable treatment-related toxicity. In this prospective interventional phase- II study, 60 patients with LAHNSCC (treatment naive), the majority in stage IVB and ECOG PS ≤ 3, were treated with QUAD SHOT RT using the conventional 2D technique (14Gy in 4 fractions on 2 consecutive days twice daily with a 6-hour interval between the two fractions) and concurrent cisplatin (CDDP) at a dose of 6 mg/m2. This treatment was repeated at 4-week intervals for 2 additional cycles if tumor progression did not occur. The Kaplan-Meier method was used to determine survival probability for progression-free survival (PFS) and overall survival (OS). Descriptive statistics with number and percentage were used for each toxicity and tumor response at different time points. A P value of less than 0.05 was considered significant. In our study, all patients received at least one cycle of QUADSHOT chemoradiotherapy (CTRT), while 35 and 18 patients received the 2nd and 3rd QUADSHOT CTRT, respectively. Of the patients who completed the first cycle of QUADSHOT CTRT, 27 (45%) patients had a partial response (PR) and 22 (36.7%) had stable disease (SD). Of the patients who completed the second cycle QUADSHOT CTRT, 77.2% had SD, while 11.4% had PR and 11.4% had PD. After the 3rd QUADSHOT CTRT, 72.2% had SD, while 11.1% had PR and 16.7% had PD. The overall response rate (SD +PR) in our study was 81%, 88.6%, and 83% after the 1st, 2nd, and 3rd QUADSHOT CTRT, respectively. After the 3rd QUADSHOT CTRT, no patient showed grade 4 toxicity. Most patients had grade I/ II toxicities e.g., skin (grade I -83%), mucositis (grade II -50%), salivary gland toxicity (grade II -50%), grade I laryngitis (83.3%). Grade- III oral mucositis and pharyngitis were seen in 27% and 6.7% of patients, respectively. Median OS and PFS were 7.9 months and 6.2 months, respectively. Concurrent chemotherapy acts as a radiosensitizer and provides a synergistic effect when coupled with hypo-fractionated radiation, resulting in more effective control of locoregional disease in locally advanced head and neck tumors with acceptable toxicities. This study is hypothesis-generating and may serve as a basis for developing optimal CTRT regimens for patients with LAHNSCC who are not suitable for curative treatment.

Aspects of hypofractionation in modern radiation oncology

Background. In the modern world, the incidence of cancer diseases is rapidly increasing and is the second most common cause of death. This is preconditioned by the quantitative growth of the senior and elderly population, as well as the growth of the main risk factors for cancer, which is related to the socio-economic development of society. About half of cancer cases require radiation therapy (RT) as a component of multimodal treatment, therefore its improvement, namely the introduction of hypofractionated radiation regimens, is considered today as one of the most effective ways to increase availability of oncological care and optimize the use of health care system resources.&#x0D; Purpose. To find out clinical and medico-social advantages of the hypofractionated approach in radiation oncology in order to optimize the functioning of the health care system by increasing availability of treatment for cancer patients. To highlight the importance of hypofractionated RT in terms of evidence-based medicine for the most common oncological pathology and in neuro-oncology. To demonstrate the influence of the COVID-19 pandemic on the implementation of hypofractionated RT. To present our own experience of using hypofractionated radiation regimens in patients with glioblastoma (GB).&#x0D; Materials and methods. MEDLINE (Pubmed), EMBASE (Ovid), Web of Science (Web of Knowledge) databases were used to search for literature. The search was performed in the English-language sources with the following keywords: «Radiation», «Hypofractionation radiotherapy», «Hypofractionated radiotherapy», «Hypofractionated irradiation»; «Breast cancer»; «Prostate cancer»; «Lung cancer»; «Glioblastoma», COVID-19. Systematic reviews, meta-analyses, randomized controlled trials and retrospective clinical trials were reviewed in full. The primary sources were backreferenced to identify additional relevant studies related to hypofractionated radiation treatment regimens. The last date of the search is 05.25.2023. The authors’ own experience of the hypofractionated approach in the adjuvant radiation treatment of patients with GB is presented briefly, as a reflection of the relevance of the authors’ practical experience to the provisions of the narrative review, based on the results of a retrospective single-center non-randomized study conducted at the State Institution «Romodanov Neurosurgery Institute National Academy of Medical Sciences of Ukraine» in 2014–2020. The oncological results of 110 (69.2%) patients of the hypofractionated RT group (15 fractions, single fraction dose (SFD) 3.5 Gy, total fraction dose (TFD) 52.5 Gy) and 49 (30.8%) patients of the standard RT group (30 fractions, RVD 2.0 Gy, SVD 60.0 Gy) were compared. RT was performed with Trilogy linear accelerator (USA) (6 MeV) using the intensity-modulated radiotherapy method (IMRT). Overall survival (OS) and recurrence-free survival (RFS) in the groups were analyzed.&#x0D; Results and discussion. Hypofractionated approaches, which allow to significantly decrease the duration of radiation treatment, have clinical, medical and social advantages, including: increased comfort for a patient; reduction of the workload on staff and technological equipment of medical facilities; reduction of the cost of treatment. The introduction of hypofractionated RT allows to increase access to cancer care at the global level, reducing disparity in the results of treatment of cancer patients between low- and middle-income countries and the countries with high income level. Hypofractionated radiation regimens are included in the clinical guidelines of professional associations, as for the most common forms of cancer and for malignant brain tumors, and represent the standard of treatment for particular clinical cases. Our experience of using the hypofractionated radiation regimen is based on the adjuvant radiation treatment of 110 patients with GB and in terms of clinical results is a relevant concept presented in a narrative review. The analysis showed no statistical difference between the groups of standard fractionation and hypofractionated RT in OS (Logrank test p = 0.06757) and RFS (Logrank test p = 0.43374). In the hypofractionation group, with an observation time median of 22.3 months, the OS median was 16.5 (95% CI 14.1–18.8) months; median RFS was 9.0 (95% CI 8.0–10.0) months. In the standard radiation regimen group, with a median of observation time of 24.4 months, the median OS was 15.0 (95% CI 14.1–17.1) months; median RFS is 9.0 (95% CI 9.0–10.0) months.&#x0D; Conclusion. Development and implementation of the measures designed to optimize the use of resources of medical facilities of Ukraine is a necessary condition for maintaining high-quality care for cancer patients in the conditions of full-scale military aggression, which has been ongoing since February 24, 2022. Increased application of hypofractionated approaches in radiation oncology can be considered as a potential tool for optimization of the use of resources of the healthcare system of Ukraine and enhancing public health.

Significance of Hypofractionated Radiotherapy in Postoperative Irradiation for Breast Cancer: An Asian Multi-institutional Prospective Study

AimsThere is a need for the adequate distribution of healthcare resources in Southeast Asia. Many countries in the region have more patients with advanced breast cancer who are eligible for postmastectomy radiotherapy (PMRT). Therefore, it is critical that hypofractionated PMRT is effective in most of these patients. This study investigated the significance of postoperative hypofractionated radiotherapy in patients with breast cancer, including advanced breast cancer, in these countries. Materials and methodsEighteen facilities in 10 Asian countries participated in this prospective, interventional, single-arm study. The study included two independent regimens: hypofractionated whole-breast irradiation (WBI) for patients who had undergone breast-conserving surgery and hypofractionated PMRT for patients who had undergone total mastectomy at a dose of 43.2 Gy in 16 fractions. In the hypofractionated WBI group, patients with high-grade factors received additional 8.1 Gy boost irradiation sessions for the tumour bed in three fractions. ResultsBetween February 2013 and October 2019, 227 and 222 patients were enrolled in the hypofractionated WBI and hypofractionated PMRT groups, respectively. The median follow-up periods in the hypofractionated WBI and hypofractionated PMRT groups were 61 and 60 months, respectively. The 5-year locoregional control rates were 98.9% (95% confidence interval 97.4–100.0) and 96.3% (95% confidence interval 93.2–99.4) in the hypofractionated WBI and hypofractionated PMRT groups, respectively. Regarding adverse events, grade 3 acute dermatitis was observed in 2.2% and 4.9% of patients in the hypofractionated WBI and hypofractionated PMRT groups, respectively. However, no other adverse events were observed. ConclusionAlthough further follow-up is required, hypofractionated radiotherapy regimens for postoperative patients with breast cancer in East and Southeast Asian countries are effective and safe. In particular, the proven efficacy of hypofractionated PMRT indicates that more patients with advanced breast cancer can receive appropriate care in these countries. Hypofractionated WBI and hypofractionated PMRT are reasonable approaches that can contain cancer care costs in these countries. Long-term observation is required to validate our findings.

A simple mathematical model of cyclic hypoxia and its impact on hypofractionated radiotherapy.

There is evidence that the population of cells that experience fluctuating oxygen levels ("acute," or, "cyclic" hypoxia) are more radioresistant than chronically hypoxic ones and hence, this population may determine radiotherapy (RT) response, in particular for hypofractionated RT, where reoxygenation may not be as prominent. A considerable effort has been devoted to examining the impact of hypoxia on hypofractionated RT; however, much less attention has been paid to cyclic hypoxia specifically and the role its kinetics may play in determining the efficacy of these treatments. Here, a simple mathematical model of cyclic hypoxia and fractionation effects was worked out to quantifythis. Cancer clonogen survival fraction was estimated using the linear quadratic model, modified to account for oxygen enhancement effects. An analytic approximation for oxygen transport away from a random network of capillaries with fluctuating oxygen levels was used to model inter-fraction tissue oxygen kinetics. The resulting survival fraction formula was used to derive an expression for the iso-survival biologically effective dose (BED), BEDiso-SF . These were computed for some common extra-cranial hypofractionated RTregimens. Using relevant literature parameter values, inter-fraction fluctuations in oxygenation were found to result in an added 1-2 logs of clonogen survival fraction in going from five fractions to one for the same nominal BED (i.e., excluding the effects of oxygen levels on radiosensitivity). BEDiso-SF 's for most ultra-hypofractionated (five or fewer fractions) regimens in a given tumor site are similar in magnitude, suggesting iso-efficacy for common fractionationschedules. Although significant, the loss of cell-killing with increasing hypofractionation is not nearly as large as previous estimates based on the assumption of complete reoxygenation between fractions. Most ultra-hypofractionated regimens currently in place offer sufficiently high doses to counter this loss of cell killing, although care should be taken in implementing single-fractionregimens.

Comparative study of concurrent conventional chemoradiotherapy versus hypofractionated chemoradiotherapy in newly diagnosed glioblastoma multiforme postoperative patients.

To assess the treatment response and toxicity profile among two groups of newly diagnosed glioblastoma multiforme (GBM) postoperative patients receiving conventional radiotherapy (RT) versus hypofractionated RT with concurrent temozolomide (TMZ) in both. A total of 50 patients randomly allotted into two arms (25 in each). Dose received 60 Gy (2 Gy/#) in conventional fractionation RT versus 50 Gy (2.5 Gy/#) in hypofractionated RT with concurrent TMZ 75 mg/m2 orally daily in both arms, respectively. Follow-up was done at 1, 3, 6, and 12 months after completion of treatment to evaluate toxicities, treatment response, and progression-free survival (PFS). All patients were well tolerated with treatment; no major adverse effects were monitored in two arms. There was no statistical significant difference in treatment response, which was found 64% versus 60% in arm A and arm B, respectively, at 3 months of follow-up (P = 0.768). Toxicity profiles were also noted similar in both arms. The 6-month PFS was 84% and 80% in arm A and arm B, respectively (P = 0.71) and 12-month PFS was 60% and 52% in arm A and arm B, respectively (P = 0.69). Among the patients followed, this study showed that hypofractionated RT regimen was not inferior to conventional RT regimen.

Comparison of two hypofractionated palliative radiation therapy schedules head and neck cancers in terms of their clinical outcomes

More than 70% of patients with locally advanced head and neck malignancies (LAHNC), poor performance status, and eligibility for palliative radiation (RT) for symptom relief present in India. In this prospective trial, patients with LAHNC at a local cancer centre in north-west India will be treated with two distinct short-course hypo-fractionated RT regimens. There were 7 females and 33 males in this study. The bulk of our study group consisted of smokers and tobacco chewers, and the majority had this habit for 20–30 years, according to the results. In our study population, there was an overall improvement in quality of life, along with improvements in pain, speech, and overall health. In conclusion, patients' quality of life significantly improved in both groups, and there was no statistically significant difference between the two. The Christie regime may be similarly helpful in treating some patients to obtain a complete response.

Flow cytometry-assisted quantification of immune cells infiltrating irradiated tumors in mice.

The immunomodulatory properties of local hypofractionated radiotherapy are known to promote the generation of anti-tumor immune responses. Such responses are largely due to the infiltration of cytotoxic lymphocytes (TILs) into the tumors that are able to destroy malignant lesions. In this context, characterizing the tumor immune microenvironment following radiotherapy is crucial for the study of its mechanism of action. Flow cytometry-based analyses are frequently used to elucidate changes in the tumor immune microenvironment. The use of a fluorochrome-conjugated antibody panel is currently a standard technique to assess the number and phenotype of immune cell populations infiltrating the tumors. Here, we describe a method to isolate and quantify TILs based on flow-cytometry in mammary carcinoma-bearing mice that undergo a local hypofractionated radiotherapy regimen consisting of 3 consecutive doses of 8Gy. With some adaptations, this protocol can be successfully applied to a diverse range of transplantable and inducible solid mouse tumors of different origins.

Dosimetric Study Comparing 3D Conformal Radiotherapy (3D-CRT), Intensity Modulated Radiotherapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT) in Hypofractionated One-Week Radiotherapy Regimen in Breast Cancer.

Introduction Recently, the one-week hypofractionated radiotherapy regimen (26 Gy in 5 fractions) for adjuvant breast radiotherapy has been shown to be non-inferior to other hypofractionated regimens (15-16 fractions). The aim of the present dosimetric study is to compare Intensity Modulated Radiotherapy (IMRT), Volumetric Modulated Arc Therapy (VMAT) and 3D Conformal Radiotherapy (3D-CRT) for a one-week hypofractionated radiotherapy regimen (26 Gy in 5 fractions) for adjuvant breast radiotherapy. Methods A total of 30 patients with histologically proven invasive carcinoma of the breast after breast conservation surgery (BCS) or modified radical mastectomy (MRM) were considered for in silico planning study. The dose prescription used was 26 Gy in 5 fractionsas used in the FAST Forward protocol. Targets were contoured according to standard guidelines. The heart, ipsilateral lung, and contralateral breast were contoured as organs at risk. Results Planning Target Volume (PTV) coverage:For IMRT, VMAT and 3D-CRT, respectively, the volumes that received at least 95% of the prescription dose (V95) were 95.7 ± 2.12, 92.47 ± 3.83, 90.87 ± 5.13; mean PTV doses (Dmean) were 26.1 ± 0.6, 25.7 ± 0.7, and 28 ± 4.39 (3D-CRT has higher Dmean compared to other techniques). Maximum PTV doses (Dmax) were 28.23 ± 0.72, 28.73 ± 0.64, and 29.8 ± 1.03. IMRT had a better V95 coverage and conformity index. Organs At Risk (OARs):The volumes that received at least 25% of the prescription dose (V25) of the heart were 3.41 ± 4.7, 1.8 ± 2.02 and 4.3 ± 6.98 in IMRT, VMAT and 3D-CRT, respectively. The volumetric (V25) comparison of heart dose in left-sided breast cancer was significantly different between VMAT and 3D-CRT (p=0.04, Wilcoxon signed-rank test). The volume that received at least 5% of the prescription dose (V5)was less than 25% in the 3D-CRT plan (12.55).For the ipsilateral lung, the V25 parameters were 19.53 ± 10.96, 23.93 ± 13.58 and 20.5 ± 12.32 in IMRT, VMAT and 3D-CRT, respectively. Conclusion From this study, we can conclude that IMRT and VMAT techniques are feasible and can achieve better dosimetric goals for target and OARs though minimizing the area achieving low dose remains to be a dosimetric concern for VMAT.

Treatment Outcomes of Postoperative Ultra-Hypofractionated Stereotactic Body Radiotherapy in Prostate Cancer

<h3>Purpose/Objective(s)</h3> Prospective randomized phase 3 trials have shown that hypofractionated radiotherapy (RT) regimens are safe and effective for definitive prostate RT. There is, however, a scarcity of data describing the outcomes of ultra-hypofractionation in the postoperative setting. The purpose of this study was to assess the safety of ultra-hypofractionated RT to prostate bed using stereotactic body RT (SBRT) technique. <h3>Materials/Methods</h3> The clinical data of 69 prostate cancer patients who received postoperative prostate bed SBRT between August 2018 and September 2020 were reviewed retrospectively. All patients had had radical prostatectomy, and 44 (63.8%) had pelvic lymph node dissection, with a median of 14 (range: 2–34) lymph nodes dissected. The primary endpoints were failure from biochemical failure (FFBF) and acute and late gastrointestinal (GI) and genitourinary (GU) toxicities. Secondary endpoint was progression free survival (PFS). <h3>Results</h3> The median age was 64 years (range: 43–76 years). Thirty patients (43.5%) received adjuvant RT and 39 (56.5%) had salvage RT median 12.4 months (range: 1.5–137.6 months) after surgery. Median SBRT fraction and total doses were 7 Gy (range: 6–7.3 Gy) and 30 Gy (30–36.5 Gy), respectively delivered in 5 days. Majority of patients (82.7%) had high risk disease and only 13 patients (18.8%) had lymph node metastasis. Seminal vesicle invasion was observed in 22 patients (31.9%) and 49 patients (71%) had extracapsular invasion. Forty-eight patients (69.6%) had positive surgical margin. Pre-SBRT and post-SBRT PSA values were 0.37 ng/mL and 0.05 ng/mL, respectively. 27 patients (39.1%) also received adjuvant androgen deprivation therapy (ADT) after SBRT and post-treatment PSA nadir value was 0.01 ng/mL. Median follow-up time was 23.8 months (range: 2.8–37.2 months). The 2-year FFBF and PFS were 91.4% and 87%, respectively. Seven patients (10.1%) had BF median 18.5 months (range: 1.7–33.5 months) after completion of SBRT. Disease progression was observed in 10 patients (14.5%) median 13.9 months after treatment. Acute GI and GU system toxicities of grade 2 or greater were observed in 13% and 14.5% of patients, respectively. Late GI and GU toxicities of grade 2 or greater were observed in 4.3% and 16% of patients, respectively. <h3>Conclusion</h3> SBRT delivered to the prostate bed over a 5-day period was found to be safe, with acceptable acute and late toxicities. Longer follow-up and randomized trials with a large patient population, however, are required to validate our findings.

Radiation Therapy for Cutaneous Squamous and Basal Cell Carcinomas of the Face Treated with HDR Brachytherapy Using Custom Thermoplastic Applicators

<h3>Purpose/Objective(s)</h3> Non-melanoma skin cancer (NMSC) of the face is prevalent and increasing in incidence with cosmetic outcome and functionality of utmost importance. We report on an underutilized modality of radiation treatment with HDR brachytherapy custom thermoplastic applicators. <h3>Materials/Methods</h3> A total of 301 cutaneous carcinomas of the face with a mean tumor size of 1.4cm (0.2cm-8cm) were treated with HDR brachytherapy Ir-192 custom thermoplastic applicators (CTA). Most commonly, hypofractionated radiation regimens included 40Gy in 8 fractions delivered twice weekly or 48Gy in 16 fractions delivered four times weekly. <h3>Results</h3> Mean follow up was 28.2 months (range, 1-149 months). Of the 301 facial lesions treated, local control was 95.7% with most recurrences being salvaged by either re-irradiation in 30.7%, wide local excision (WLE) 23.1%, or Moh's micrographic surgery 23.1%. 65% were basal cell carcinomas and the most common sites of disease were the nose (33.9%), cheek (20.9%), forehead (18.6%), and ear (17.3%). At first follow up, Grade 0-1 acute radiation dermatitis was observed in 66.1% of lesions, grade 2 in 27.4%, grade 3 in 6.2% (n=18) and grade 4 toxicity was seen in one patient (0.34%). Chronic toxicity included erythema (8.2%), fibrosis (7.4%), telangiectasia (4.1%), and hypo/hyperpigmentation (1.7%). No patients exhibited chronic ulcers. The median number of catheters used was 4 (range, 1-17), and the largest diameter treated was a median of 2.5cm (0.2-14.2cm). <h3>Conclusion</h3> Non-melanoma skin cancer of the face can be successfully treated with HDR brachytherapy custom thermoplastic applicators with low toxicity and excellent outcomes.

Hypofractionated versus conventional intensity-modulated radiation irradiation (HARVEST-adjuvant): study protocol for a randomised non-inferior multicentre phase III trial

IntroductionShort course regimen has become the major trend in the field of adjuvant radiotherapy for patients with breast cancer. Hypofractionated radiotherapy (HF-RT) regimen of 40–42.5 Gy in 15–16 fractions has...

Sequential Hypofractionated versus Concurrent Twice-Daily Radiotherapy for Limited-Stage Small-Cell Lung Cancer: A Propensity Score-Matched Analysis.

Simple SummaryAlthough twice-daily concurrent chemoradiotherapy for limited-stage small-cell lung cancer (LS-SCLC) is still the standard treatment, this regimen is inconvenient and not universally adopted across different institutions. Therefore, the optimal radiation dose and fractions are still under investigation. A once-daily hypofractionated schedule may be suitable for LS-SCLC patients, and more and more hypofractionated schedule studies are being performed. However, few studies have investigated the efficacy and toxicities of sequential chemotherapy and hypofractionated radiotherapy compared with the concurrent twice-daily schedule. Our evaluation of sequential hypofractionated and twice-daily concurrent chemoradiotherapy schedules before and after propensity score-matched analysis (PSM) for LS-SCLC revealed a comparable survival and less toxicity. The sequential hypofractionated schedule may be used as an alternative to concurrent twice-daily regimens.Background: As there are no randomized trials comparing twice-daily with sequential hypofractionated (sequential hypo) radiotherapy regimens for limited-stage small-cell lung cancer (LS-SCLC). This study aimed to compare these two regimens for LS-SCLC by propensity score-matched analysis (PSM). Methods: We retrospectively analyzed 108 LS-SCLC patients between January 2015 and July 2019. All patients received concurrent twice-daily or sequential hypo radiotherapy. The survival, failure patterns, and toxicities were evaluated before and after PSM. Results: Before PSM, multivariate analysis showed that patients treated with sequential hypo had a significantly better overall survival (OS) and distant metastasis-free survival (DMFS) (HR = 0.353, p = 0.009; HR = 0.483, p = 0.039, respectively). Total radiotherapy time ≥ 24 days and stage III (HR = 2.454, p = 0.004; HR = 2.310, p = 0.004, respectively) were poor prognostic indicators for OS. Patients with a total radiotherapy time ≥ 24 days and N2–3 were more likely to recur than others (HR = 1.774, p = 0.048; HR = 2.369, p = 0.047, respectively). N2–3 (HR = 3.032, p = 0.011) was a poor prognostic indicator for DMFS. After PSM, being aged ≥65 years was associated with poorer OS, relapse-free survival (RFS) and DMFS (p < 0.05). A total radiotherapy time of ≥24 days was a poor prognostic indicator for OS and RFS (HR = 2.671, p = 0.046; HR = 2.370, p = 0.054, respectively). Although there was no significant difference, the patients in the sequential hypo group had a trend towards a better OS. The failure pattern between the two groups showed no difference. More patients had grade 1–2 esophagitis in the twice-daily group (p = 0.001). Conclusions: After propensity matching, no difference was shown in survival and failure. The sequential hypo schedule was associated with comparable survival and less toxicity and may be used as an alternative to concurrent twice-daily regimens.