Hypofractionated-accelerated Radiotherapy Research Articles

Comparison of Two Phase II Trials of Neoadjuvant Temozolomide Followed with Concomitant and Adjuvant Temozolomide and Hypofractionated Accelerated Radiotherapy with or without Metformin in Patients with Newly Diagnosed Glioblastoma

<h3>Purpose/Objective(s)</h3> Metformin (MTF) inhibits the proliferation of Glioblastoma (GBM) cells by activating adenosine monophosphate-activated protein kinase (AMPK), and mTOR, with subsequent sensitization to ionizing radiation and Temozolomide (TMZ). Furthermore, MTF reduces blood glucose levels and growth factors including insulin and insulin-growth factors. <h3>Materials/Methods</h3> Each trial consisted of 50 adults with newly diagnosed GBM. Within 4-5 weeks from surgery patients received either: (1) neo-adjuvant TMZ (75 mg/m²PO QD) for 2 weeks prior to Hypofractionated Accelerated Radiotherapy (HART) (60 Gy in 20 daily fractions over 4 weeks) given with concomitant and adjuvant TMZ given for 6 cycles at 150–200 mg/m² (N-HART) trial ClinicalTrials.gov NCT # NCT01702610; or (2) neo-adjuvant TMZ (75 mg/m²PO QD) + MTF (850 mg PO BID) for 2 weeks prior to HART with concomitant and adjuvant MTF + TMZ. Adjuvant TMZ + MTF were given for 6 cycles ClinicalTrials.gov NCT # 02780024. Survival analyses were done according to the Kaplan-Meier methods and Log-rank statistics. <h3>Results</h3> The median follow up for patients at risk was 107.9 months for the N-HARTT, and 34.3 months for the M-HARTT trials. The 2 cohorts were balanced for age and ECOG status. Gross total resection was performed in 54% of N-HARTT versus 84% in M-HARTT cohort. MGMT-gene promoter was methylated in 48% in N-HARTT trial compared to 32% in the M-HARTT trial. The median overall survival (OS) and PFS were 22.3 months, and 13.7 months, respectively for the N-HARTT trial compared with 29.5 months, and 13.7 months for the M-HARTT cohort [p=0.22 HR 0.91 (95% CI 0.56-1.47)]. Patients with unmethylated MGMT tumors had a median OS of 15 months in the N-HARTT trial compared to 24 months for patients with unmethylated MGMT tumors treated on the M-HARTT trial [(p=0.07 HR 0.64 (CI 95% 0.35-1.17)]. Patients with methylated MGMT tumors had 46.3 months median OS versus 50 months for patients with methylated MGMT tumors treated on N-HARTT and M-HARTT trials, respectively [(p=0.25 HR 1.37 (CI 95% 0.88-2.15)]. In a sub-group analysis of the M-HARTT trial, we observed that the median OS of patients with an average blood glucose levels of < 5 mmol/L has not been reached versus a median OS of 25.7 months for patients with blood glucose levels ≥ 5 mmol/L, (p=0·03 HR 0·30 95%CI, 0·13–0.67 Log-rank) <h3>Conclusion</h3> The addition of MTF in the M-HART trial resulted in an encouraging improvement of the median OS compared with N-HART trial. The main impact was observed in patients with unmethylated MGMT tumors. Furthermore, the results are suggestive for a potential role for glycemic control on outcomes.

Postoperative hypofractionated-accelerated radiotherapy (HypoAR) for locally advanced rectal cancer.

despite the advances in preoperative hypofractionated-accelerated radiotherapy for patients with locally advanced rectal cancer, postoperative radiotherapy delivered with standard fractionation (46-50 Gy in 5weeks) remains a standard adjuvant schedule. The role of hypofractionated-accelerated radiotherapy in a postoperative setting remains largely unexplored. eighty-eight patients with rectal cancer infiltrating the rectal wall and/or having metastasis to the perirectal lymph nodes were treated with surgery followed by adjuvant chemotherapy and, subsequently, with hypofractionated-accelerated radiotherapy. Ten fractions of 3.4 Gy were delivered to the pelvis for 10 consecutive fractions, within 12days. The follow-up of patients alive at the time of analysis ranges from 12-120months (median 48). mild abdominal discomfort and diarrhoea were frequent, but medical medication was demanded in 14/88 (15.9%) of patients. The incidence of late toxicities was low; 4/88 (3.5%) patients complained for intermittent intestinal urgency. Locoregional recurrence occurred in 8/88 patients (9%). The 5-year locoregional relapse-free survival was achieved in 89.7% of patients, and this dropped to 84% in node-positive patients (P=0.45). The 5-year disease-specific overall survival was 72.4%. Nodal involvement showed a trend to negatively affect prognosis (5-year overall survival 68.2 vs. 79.6%; P=0.23). postoperative hypofractionated-accelerated radiotherapy has minimal early and late toxicity. The locoregional control and disease-specific survival rates are similar to the expected from conventional postoperative chemoradiotherapy. The 2.5-fold decrease of radiotherapy treatment time, reduction of waiting lists and the lower overall cost of radiotherapy are additional benefits associated with hypofractionated-accelerated radiotherapy.

A Phase 2 Study of Neo-adjuvant Metformin and Temozolomide followed by Hypofractionated Accelerated RadioTherapy (HART) with Concomitant and Adjuvant Metformin and Temozolomide (TMZ) in Patients with Glioblastoma

Metformin inhibits the proliferation of glioblastoma (GBM) cancer stem cells through stimulation of AMPK, lowers glucose levels, insulin, and IGF-1. The purpose was to assess the feasibility of post-op neo-adjuvant metformin and TMZ, followed by HART with concomitant and adjuvant TMZ/metformin. Neo-adjuvant metformin (850 mg BID) and TMZ (75 mg/m2 QD) were started within 4 weeks from surgery, for 14 days prior to starting radiotherapy. HART was delivered using IMRT simultaneous boost technique. The CTV included surgical resection cavity and post-operative residual contrast enhancing lesion. The PTV_60 included CTV+3-5 mm margin, while PTV_40 included CTV + 15 mm. A dose of 60 Gy was delivered to PTV_60 while a dose of 40 Gy was delivered to PTV_40 in 20 daily fractions. Concomitant and adjuvant TMZ were administered as per the Stupp’s schedule with concomitant metformin. Thirty-three patients, 19 females and 14 males were included. Median age was 54 years, median ECOG score was 1 At a median follow-up of 20.3 months (range 2.0-55.8) for patients at risk, the median survival was 38.2 months (95% CI, 12-59), with 20 out of 33 patients alive at the date of this report. At 2 years the overall survival was 65.5%, and 50.5 % at 3 years. Median PFS was 15.4 months (95% CI, 10-36). For 27 patients with gross total resection, median survival was 38.84 months compared to 16.8 months for 6 patients with partial resection (p = 0.02). The median survival of patients aged < 60 years was 38.8 months and 17.1 for patients > 60 years (p = 0.16). The median survival for 12 patients with methylated MGMT was not reached compared to 38.2 months for 21 patients with unmethylated MGMT (p = 0.12). Adjuvant TMZ/Metformin was discontinued in 2 patients, one with disease progression, and another one following prolonged grade 4 thrombocytopenia. There were no unexpected severe adverse events. Thirteen patients were re-operated for findings suggestive of disease progression. Six patients of the 13 re-operated patients had treatment-related necrosis with no viable residual GBM. Two of these 6 patients later developed disease progression. Eighty-one percent and 70.9% of the patients were free from treatment-related necrosis at 2 and 3 years, respectively. Neo-adjuvant metformin and TMZ followed by concurrent TMZ/metformin and HART and adjuvant TMZ/metformin is feasible and safe, and the results compare favorably to current GBM literature, especially for patients with unmethylated MGMT.

Resource-sparing curative-intent hypofractionated-accelerated radiotherapy in head and neck cancer: More relevant than ever before in the COVID era.

The incidence of head and neck squamous cell carcinoma (HNSCC) is increasing worldwide, with over three quarters of cases now diagnosed in low and middle-income countries (LMICs) with resource-constraints. Loco-regional recurrence remains the predominant pattern of failure mandating adequate local therapy for acceptable loco-regional control and survival. There is high-quality evidence that intensification of treatment by either by adding concurrent chemotherapy or by altering radiotherapy (RT) fractionation improves outcomes in the curative-intent management of loco-regionally advanced HNSCC. Even conservative estimates indicate that >50% of patients in LMIC are unlikely to get access to timely RT, which will only get compounded with the coronavirus disease (COVID)-19 pandemic. The radiation oncology community has been systematically testing altered fractionation schedules in several solid cancers (breast, lung, and head-neck), given the cost-effectiveness, convenience, and compliance to short-course RT regimens. Radiobiological modelling suggests that standard fractionation of 6-7weeks in HNSCC can be compressed safely into a 4-week schedule to counter accelerated repopulation by increasing the dose per fraction and delivering 5 fractions per week which is currently being tested in the ongoing multicentric trial of hypo- vs normo-fractionated accelerated RT (HYPNO study). Herein, we discuss the radiobiological basis of curative-intent hypofractionated-accelerated RT schedule delivering 55Gy in 20 fractions over 4weeks in HNSCC followed by critical appraisal of the published literature on such regimens with concurrent systemic therapy and its inherent resource-sparing potential applicable across large parts of the world particularly in the context of the ongoing COVID-19 pandemic.

Hypofractionated accelerated radiotherapy (HART) with concurrent and maintenance temozolomide in newly diagnosed glioblastoma: a phase II randomized trial (HART-GBM).

e14090Background: To compare Overall Survival (OS) between Hypofractioanted accelerated radiotherapy (HART) and Conventional fractionated radiotherapy (CRT) in newly diagnosed GBM. Methods: Patient...

PO-0728: Postoperative hypofractionated-accelerated radiotherapy in prostate cancer: a phase I-II study (ISIDE-PP-2)

PO-0728: Postoperative hypofractionated-accelerated radiotherapy in prostate cancer: a phase I-II study (ISIDE-PP-2)

Short-course radiotherapy in elderly patients with glioblastoma: feasibility and efficacy of results from a single centre

The incidence of glioblastoma (GBM) in the elderly population is currently increasing, with a peak seen between 65 and 84years. The optimal treatment in terms of both efficacy and quality of life still remains a relevant and debated issue today. The purpose of our study was to evaluate the feasibility of short-course hypofractionated accelerated radiotherapy (HART) in GBM patients aged over 70years and with a good Karnofsky performance score (KPS). A review of medical records at the "Istituto Neurologico C. Besta" was undertaken; patients aged ≥ 70years who had undergone adjuvant HART for GBM between January 2000 and January 2004 were included in the study. HART was administered to a total dose of 45Gy, 2.5Gy/fraction, in three daily fractions for three consecutive days/cycle fractions each, delivered in two cycles (split 15days). A total of 33patients were evaluable for the current analysis. Median follow-up was 10months. According to CTCAE (version 3.0) criteria, none of the patients developed radiation-induced neurological status deterioration or necrosis. KPS evaluation after HART was found to be stable in 73 % of patients, improved in 24 %, and worse in 3 %. The median overall survival time of the entire study population was 8months (range 2-24). Our findings suggest that a hypofractionated accelerated schedule can be a safe and effective option in the treatment of GBM in the elderly.

P29 Hypofractionated-accelerated radiotherapy with concurrent cisplatin in locally advanced oral cancer

P29 Hypofractionated-accelerated radiotherapy with concurrent cisplatin in locally advanced oral cancer

1018 poster Local treatment of osteogenic sarcoma (OS) with hypofractionated-accelerated radiotherapy (HA-RT)

1018 poster Local treatment of osteogenic sarcoma (OS) with hypofractionated-accelerated radiotherapy (HA-RT)

Pain Relief with Short Term Irradiation in Locally Advanced Carcinoma of the Pancreas

To evaluate whether a short radiation treatment (30 Gy, 3.0 Gy/fraction) had analgesic efficacy in patients with unresectable pancreatic carcinoma. Twelve patients were included in this analysis. Before starting and at four weeks after radiation therapy, pain intensity was evaluated and analgesic drug therapy was adjusted until a 0-3 pain score was reached (WHO). No radiotherapy interruptions, no hospitalisation due to toxic reactions, and no severe toxicity were observed. Six patients (50%) had pain control without pharmacological therapy, three patients (25%) reduced their use (35%-72%) of analgesics, while in the remaining three patients (25%) there was no change in analgesic use. Overall, mean reduction in the use of analgesics was 63.1% +/- 43.8%. During follow-up (44 months), two patients (16.7%) showed a worsening of pain that required increased analgesia; in one patient, percutaneous splanchnicectomy was necessary. In patients excluded from standard concomitant chemoradiation, hypofractionated-accelerated radiotherapy is feasible and results in pain relief in most patients, documented as a reduced need for analgesics.