Radiation Fractionation Schedules Research Articles

Targeting the Tumor Vascular Supply to Enhance Radiation Therapy Administered in Single or Clinically Relevant Fractionated Schedules

This pre-clinical study was designed to demonstrate how vascular disrupting agents (VDAs) should be administered, either alone or when combined with radiation in clinically relevant fractionated radiation schedules, for the optimal anti-tumor effect. CDF1 mice, implanted in the right rear foot with a 200 mm3 murine C3H mammary carcinoma, were injected with various doses of the most potent VDA drug, combretastatin A-1 phosphate (CA1P), under different schedules. Tumors were also locally irradiated with single-dose, or stereotactic (3 × 5–20 Gy) or conventional (30 × 2 Gy) fractionation schedules. Tumor growth and control were the endpoints used. Untreated tumors had a tumor growth time (TGT5; time to grow to 5 times the original treatment volume) of around 6 days. This increased with increasing drug doses (5–100 mg/kg). However, with single-drug treatments, the maximum TGT5 was only 10 days, yet this increased to 19 days when injecting the drug on a weekly basis or as three treatments in one week. CA1P enhanced radiation response regardless of the schedule or interval between the VDA and radiation. There was a dose-dependent increase in radiation response when the combined with a single, stereotactic, or conventional fractionated irradiation, but these enhancements plateaued at around a drug dose of 25 mg/kg. This pre-clinical study demonstrated how VDAs should be combined with clinically applicable fractionated radiation schedules for the optimal anti-tumor effect, thus suggesting the necessary pre-clinical testing required to ultimately establish VDAs in clinical practice.

Salvage Breast-Conserving Surgery and Reirradiation With Intraoperative Electrons for Recurrent Breast Cancer: A Multicentric Study on Behalf of Italian Association of Radiotherapy and Clinical Oncology

AimIntraoperative radiotherapy with electrons (IOERT) may represent a viable choice for partial breast re-irradiation (rePBI) after repeat quadrantectomy for local recurrence (LR) for primary breast cancer (BC) in lieu of mastectomy. Materials and MethodsA database collecting data on rePBI with IOERT from 8 Italian centres was set up in 2016- 2018, providing data on cumulative incidence (CumI) of 2nd LR nd survival with a long follow-up (FU) ResultsFrom 2002 to 2015, 109 patients underwent the conservative retreatment.The median primary BC -1stLR interval was 11.1 years (range: 2.4-27.7). The median 1stLR size was 0.9 cm (range: 0.3-3.0) and 43.6% were Luminal A. Median IOERT dose was 18 Gy (range: 12-21) and median collimator was 4 cm (range: 3-6). Median FU was 11.7 years (interquartile range: 7.7-14.6). The 2ndLR CumI was 12.2% (95% CI: 6.8-19.2) at 5 years and 32.3% at 10 years (95% CI: 22.8-42.2), occurring in the same site as the 1stLR in about half of the cases. HER2 status and collimator size were independent LR predictors. The 5- and 10-year overall survival were 95.2% and 88.3%, respectively, while 5- and 10-year BC specific survival were 98% and 94.5%. The development of a 2ndLR significantly reduced BCSS (HR=9.40, P<0.001). Grade ≥3 fibrosis was 18.9%. Patient-reported cosmesis was good/excellent in 59.7% of the cases. Conclusion2ndLR CumI was within the range of the literature, but higher than expected, opening questions on radiation field extension and fractionation schedule. Since a 2ndLR worsened the outcome, salvage modality must be carefully planned.

Osteolytic Bone Metastasis: Different Radiotherapy Fractionation Schedules Compared Clinically and Radiographically.

The purpose of this study is to compare three commonly used radiotherapy fractionation schedules for bone metastasis in terms of clinical and radiological effectiveness. A total of 93 patients with osteolytic bone metastasis were randomized to receive 8 Gyin a single fraction (group A), 20 Gy in 5 fractions (group B) and 30 Gy in 10 fractions (group C). Changes in bone density were measured using the Relative Electron Density (RED) type corrected by Thomas (pe = HU/1.950 + 1.0), where HU is Hounsfield Units. Pain response was assessed according to the Brief Pain Inventory tool. Quality of life was estimated using the EORTC QLQ-C30 and the MD Anderson Symptom (MDAS) tools.After RT, RED, together with the parameters of EORTC QLQ-C30, MDAS and SAT, significantly increased in all groups (p < 0.001).Specifically, the increase of RED was higher in group C compared to group Athree months post-RT (p = 0.014). Group C was also superior to group A in terms of QoL and BPI three months post-treatment. Multifractionated radiotherapy for osteolytic bone metastasis is superior to single fraction radiotherapy in terms of improvement in quality of life and bone remineralization three months post-RT.

Activation of Stimulator of Interferon Genes (STING): Promising Strategy to Overcome Immune Resistance in Prostate Cancer.

Prostate cancer (PCa) is the most frequent and second-lethal cancer among men. Despite considerable efforts to explore treatments like autologous cellular immunotherapy and immune checkpoint inhibitors, their success remains limited. The intricate tumor microenvironment (TME) and its interaction with the immune system pose significant challenges in PCa treatment. Consequently, researchers have directed their focus on augmenting the immune system's anti-tumor response by targeting the STimulator of the Interferon Genes (STING) pathway. The STING pathway is activated when foreign DNA is detected in the cytoplasm of innate immune cells, resulting in the activation of endoplasmic reticulum (ER) STING. This, in turn, triggers an augmentation of signaling, leading to the production of type I interferon (IFN) and other pro-inflammatory cytokines. Numerous studies have demonstrated that activation of the STING pathway induces immune system rejection and targeted elimination of PCa cells. Researchers have been exploring various methods to activate the STING pathway, including the use of bacterial vectors to deliver STING agonists and the combination of radiation therapy with STING agonists. Achieving effective radiation therapy with minimal side effects and optimal anti-tumor immune responses necessitates precise adjustments to radiation dosing and fractionation schedules. This comprehensive review discusses promising findings from studies focusing on activating the STING pathway to combat PCa. The STING pathway exhibits the potential to serve as an effective treatment modality for PCa, offering new hope for improving the lives of those affected by this devastating disease.

HDAC-Mediated Glial Crosstalk Mediates Radiation Induced Memory Changes from Whole Brain Radiation in a Mouse Model

Prior work demonstrated radiation sensitivity can be regulated via Class III HDAC-mediated intracellular DNA damage response coordinated with Wnt-beta catenin signaling. We hypothesized that radiation induced functional alterations in HDAC mediated glial crosstalk in the CNS produce intercellular signaling alterations leading to phenotypic changes in cognition following whole brain radiation exposure. Primary human astrocytes, human astrocytoma (U251), and immortalized human microglia (HMC3) were examined in vitro in response to treatment with conditioned media isolated from irradiated glial cells. Prior to treatment with either single-dose or fractionated radiation schedules, cells were transfected with siRNA expression vector for Sirt2, a class III HDAC, versus scrambled controls. Quantitative PCR and immunoblots for neurotransmitters, metabolism, and inflammatory markers were obtained. Cells exposed to conditioned media were examined by immunofluorescence for cytoskeletal alterations and changes in junctional proteins. The findings were correlated with in vivo qPCR and immunohistochemical changes in brain tissue and functional memory changes in Sirt2 knockout versus wild type mice after whole brain radiation using novel object recognition testing at 2 weeks and 6 month post radiation timepoints. Statistical analysis was performed using paired Students T test between treated and control groups. Cells treated with conditioned media produced from irradiated U251, astrocytes and microglia produced increased expression of inflammatory cytokines IL-6, IL-8, GM-CSF and VEGF. However, immunofluorescence of cells treated with conditioned media from irradiated Sirt2 knockdown microglia and primary astrocytes demonstrated qualitative disruptions in glutamate neurotransmitter metabolism and actin cytoskeletal alterations with changes in pseudopodia and lamellipodia after staining with phalloidin and neurofilament L, suggesting altered intercellular communication. Connexin 43 in gap junctions was increased >2-fold (p<0.05) after exposure to conditioned media, whereas E-cadherin in adherens junctions was not significantly affected. Novel object recognition testing of Sirt2 knockout mice demonstrated resistance to radiation induced memory decline from whole brain radiation at pre radiation day 5 versus post radiation days 5 and 185 compared to controls (p<0.05). Glial crosstalk can be mediated via elimination of a Class III HDAC and appears to be a key mediator of radiation induced disruptions of intercellular communication in the CNS, connecting radiation to structural changes on the cell surface to synaptic activity and neurotransmitter metabolism, leading to functional disputations in recognition memory similar to what is experienced by patients receiving brain radiotherapy. These data suggest glial cross talk as a new therapeutic avenue to combat radiation induced cognitive dysfunction.

Quantitative and Qualitative Impact of CT-Based Radiotherapy Dose Maps on Radiologists' Interpretation of Post-treatment Thoracic Surveillance Imaging

For diagnostic radiologists, interpretation of surveillance imaging for oncology patients treated with radiation therapy (RT) can be challenging because (1) the imaging order may not adequately describe the radiation fields and (2) RT treatment effect and progression can appear similar. Volumetric dose visualization used for plan review is often inaccessible to radiologists. We hypothesize that displaying RT dose would improve radiologists' confidence and ability to correctly identify and distinguish irradiated targets and treatment effects. CT images were read by a board-certified cardiothoracic radiologist and a diagnostic radiology resident. The readers interpreted pre-RT, treatment planning, and 3-4 month post-RT CT images in anonymized software sessions first without, then-after a 1 month "washout" period-with access to RT dose overlay. Six color-coded isodose lines ranging from 25% to 110% represented in absolute cGy were displayed along with a brief clinical history. RT fractionation schedules ranged in BED10 from 39 to 112.5 Gy. Readers were asked to label the treated lesion(s) and treatment effect(s), and record their confidence using a Likert scale of 1-5 and agreement with statements using yes/no responses. Two readersindependently interpreted imaging for 32 patients who received thoracic RT to 1-5 lesion(s) for primary (24) or metastatic (8) cancer. Nineteen patients had 1 lesion and 13 patients had >1 lesion. Correct identification of all treated lesions significantly increased with the addition of dose visualization (61% to 81%; McNemar test, p = 0.00079), with the largest increase noted for cases with >1 lesion (15% to 54%; McNemar test, p = 0.0039). With the addition of dose information, the number of false negatives attributable to missed extranodal targets fell from 52% to 18%. Without dose information, 13% of labeled lesions and treatment effects fell outside of the 25% isodose lines, representing false positives. With the addition of dose information, false positives fell below 2% for both lesions and treatment effects. The readers' confidence that they had identified treated lesion(s) increased from a rating of 4.1 to 4.8 on a scale of 1-5 (Paired two-tail t test; p = 0.000005). Whendiagnostic radiologists have access to dose visualization, correct identification rate of irradiated lesions and treatment effects, as well as confidence in these identifications significantly increased. The decrease in false negatives could reduce potential missed identification of tumor progression while the decrease in false positives could reduce inaccurate identification of treatment failure in a new or stable lesion. Our results demonstrate that adding volumetric visualization of dose to imaging could improve quality of surveillance care for patients with irradiated thoracic malignancies.

Precision radiation oncology in head and neck cancer: beyond physical precision - a narrative review

Radiotherapy is an integral part of the management of head and neck cancers, both in radical and adjuvant settings. Traditionally, similar radiation dose and fractionation schedules have been used based on tumor stage with variable outcomes indicating “one size does not fit all”. In the era of precision medicine, though we have achieved physical precision with technological advancements, we have yet to attain biologic precision. In the current review, we have highlighted the different aspects of precision oncology such as hypoxia targeting, radiomics and radiogenomics, radiobiologic targeting, and big data. The review also discusses various potential therapeutic targets and approaches in head and neck cancer management that might help to increase radiosensitization, which in turn increase survival, and quality of life. This can be incorporated into the armamentarium of radiation oncology in all the phases of radiation planning, from diagnosis to treatment to the prognosis and management of long-term side effects. Biologic precision can be applied in the clinic to provide individualized, personalized treatment in the future.

Effect of Radiation Schedule on Transportation-Related Carbon Emissions: A Case Study in Rectal Cancer

The health care sector is a major contributor of worldwide greenhouse gas (GHG) emissions. Indirect emissions, including those associated with transportation, make up 82% of the US health care sector's environmental footprint. Radiation therapy (RT) treatment regimens present an opportunity for environmental health care-based stewardship owing to the high incidence of cancer diagnosis, significant utilization of RT, and myriad treatment days required for curative regimens. Because the use of short-course RT (SCRT) in the treatment of rectal cancer has demonstrated noninferior clinical outcomes compared with conventional, long-course RT (LCRT), we investigate the environmental and health equity-related outcomes. Patients treated with curative, preoperative RT for newly diagnosed rectal cancer at our institution between 2004 and 2022 and living in-state were included. Travel distance was estimated using patients' reported home address. Associated GHG emissions were calculated and reported in carbon dioxide equivalents (CO2e). Of 334 patients included, the total distance traveled for the treatment course was significantly greater in patients treated with LCRT versus SCRT (median, 1417 vs 319 miles; P < .001). Total CO2e emissions for those undergoing LCRT (n=261) and SCRT (n=73) were 665.3 kg CO2e and 149.9 kg CO2e, respectively, per treatment course (P < .001), with a net difference of 515.4 kg CO2e. Relatively, this suggests that LCRT is associated with 4.5 times greater GHG emissions from patient transportation. Using treatment of rectal cancer as proof-of-principle, we advocate for the inclusion of environmental considerations in the creation of climate-resilient oncologic RT practices, especially in the context of equivocal clinical outcomes between RT fractionation schedules.

A comparative and prospective study of two different radiation fractionation schedules with concurrent chemotherapy in locally advanced head-and-neck squamous cell carcinoma

Background: Accelerated fractionation radiotherapy has radiobiological advantage of preventing accelerated tumor repopulation and logistic advantage of treating more patients than conventionally fractionated radiotherapy because of its relatively shorter treatment duration. Aims and Objectives: In this study, we compared accelerated fractionation with conventionally fractionated radiotherapy in terms of tumor response and acute toxicities for the treatment of locally advanced head-and-neck carcinomas. Materials and Methods: Patients with Stage III and IVA carcinoma of head-and-neck region were randomized into two groups. The study group patients received accelerated radiotherapy to a total dose of 66Gy in 33 fractions, 2Gy/fraction, 6 fractions/week over a time period of 5.5 weeks. Control group received conventionally fractionated radiotherapy to same total dose and fraction size but 5 fractions/week, over a time period of 6.5 weeks. Both groups received concurrent weekly Cisplatin. All patients were followed up weekly for treatment related acute toxicity during the treatment and then at every month for 6 months after completion of treatment. Results: About 26.6% patients of study arm achieved complete response in comparison to 25.6% of control arm, but the difference was not statistically significant (P=0.957). Although statistically not significant, higher grade of skin toxicity (60%vs.35%, P=0.179) and xerostomia (46% vs. 29%, P=0.155) was also numerically higher in accelerated fractionation. Conclusion: For locally advanced head-and-neck carcinoma, accelerated fractionation radiotherapy with concurrent chemotherapy can be considered as an acceptable and effective alternative of conventionally fractionated concurrent chemoradiotherapy in terms of treatment response and acute toxicity profile.

A PROSPECTIVE INTERVENTIONAL STUDY TO COMPARE THE TREATMENT OUTCOMES IN PATIENTS WITH TWO DIFFERENT FRACTIONATION SCHEDULE OF WHOLE BRAIN RADIOTHERAPY WITH MULTIPLE BRAIN METASTASES

Purpose of study : To compare the treatment outcomes in patients with brain metastasis treated with two different fractionation schedules of whole brain radiotherapy. A prospective randomised study was carried out on newly diagnosed cancer patients with MRIMaterials and methods: diagnosis of brain metastasis. Patients with multiple bm with Eastern Cooperative Oncology Group performance status 0-4 were included. In Arm A, patients received whole brain radiotherapy (WBRT) of total dose 30 GY , 3Gy/fraction/10# over 2 weeks ,whereas , in Arm-B patients received total dose of 20 GY in 4Gy/fraction/5# over 1 week. Assessment of improvement in clinical symptoms was done using BARTHEL'S ADJUSTED DAILY LIVE (ADL)14 Score before treatment, just after treatment and 6 week of treatment and improvement was analysed. At three months follow up , radiological response was carried out by MRI scan of brain. Acute toxicities were assessed during treatment and follow up ( up to 90 days post EBRT ) using clinical status, laboratory investigations and radiological test and graded according to RTOG/EORTC criteria. Results: Signicant improvement in terms of ADL score was observed in both arms , however when both arms were compared , no signicant difference was found out. There was no statistically signicant difference in response or morbidity between the two treatment arms. In theConclusions: palliative setting short duration of treatment with minimum discomfort to the patient is desirable. 20 Gy in 5 fractions is equally effective as 30 Gy in 10 fractions, with slight advantage in terms of toxicity. Thus 20 Gy in 5 fractions can be preferred in brain metastasis patients, especially those with poor performance status.

Radiation doses and fractionation schedules in non-low-risk ductal carcinoma in situ in the breast (BIG 3–07/TROG 07.01): a randomised, factorial, multicentre, open-label, phase 3 study

Whole breast irradiation (WBI) after conservative surgery for ductal carcinoma in situ (DCIS) reduces local recurrence. We investigated whether a tumour bed boost after WBI improved outcomes, and examined radiation dose fractionation sensitivity for non-low-risk DCIS. The study was an international, randomised, unmasked, phase 3 trial involving 136 participating centres of six clinical trials organisations in 11 countries (Australia, New Zealand, Singapore, Canada, the Netherlands, Belgium, France, Switzerland, Italy, Ireland, and the UK). Eligible patients were women aged 18 years or older with unilateral, histologically proven, non-low-risk DCIS treated by breast-conserving surgery with at least 1 mm of clear radial resection margins. They were assigned to one of four groups (1:1:1:1) of no tumour bed boost versus boost after conventional versus hypofractionated WBI, or randomly assigned to one of two groups (1:1) of no boost versus boost after each centre prespecified conventional or hypofractionated WBI. The conventional WBI used was 50 Gy in 25 fractions, and hypofractionated WBI was 42·5 Gy in 16 fractions. A boost dose of 16 Gy in eight fractions, if allocated, was delivered after WBI. Patients and clinicians were not masked to treatment allocation. The primary endpoint was time to local recurrence. This trial is registered with ClinicalTrials.gov (NCT00470236). Between June 25, 2007, and June 30, 2014, 1608 patients were randomly assigned to have no boost (805 patients) or boost (803 patients). Conventional WBI was given to 831 patients, and hypofractionated WBI was given to 777 patients. Median follow-up was 6·6 years. The 5-year free-from-local-recurrence rates were 92·7% (95% CI 90·6-94·4%) in the no-boost group and 97·1% (95·6-98·1%) in the boost group (hazard ratio 0·47; 0·31-0·72; p<0·001). The boost group had higher rates of grade 2 or higher breast pain (10% [8-12%] vs 14% [12-17%], p=0·003) and induration (6% [5-8%] vs 14% [11-16%], p<0·001). In patients with resected non-low-risk DCIS, a tumour bed boost after WBI reduced local recurrence with an increase in grade 2 or greater toxicity. The results provide the first randomised trial data to support the use of boost radiation after postoperative WBI in these patients to improve local control. The international scale of the study supports the generalisability of the results. National Health and Medical Research Council of Australia, Susan G Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society, Canadian Cancer Trials Group.

Low-dose localised electron radiotherapy in a case of refractory mycosis fungoides

We present a case of refractory mycosis fungoides (MF) that responded to low-dose localised electron radiotherapy. A 59-year-old man presented with a 5-year history of a generalised, pruritic, scaly, red skin rash that had recently become more nodular. Skin biopsy confirmed MF. After a variable initial response to topical steroids and oral methotrexate, progressive tumours were treated with low-dose electron radiotherapy. We describe the clinical effect of different radiation doses and fractionation schedules applied over a 2-year period. Our experience in this case of MF suggests that low-dose localised electron radiotherapy offers excellent palliation by effectively resolving tumorous lesions, improving quality of life and allowing for retreatment of refractory lesions.

Hypofractionation in Hepatocellular Carcinoma – The Effect of Fractionation Size

The use of stereotactic body radiotherapy (SBRT) in hepatocellular carcinoma (HCC) has increased over the years. Several prospective studies have demonstrated its safety and efficacy, and randomised trials are underway. The advancement in technology has enabled the transition from three-dimensional conformal radiotherapy to highly focused SBRT. Liver damage is the primary limiting toxicity with radiation, with the incidence of grade 3 varying from 0 to 30%. The reported radiotherapy fractionation schedule for HCC, and in practice use, ranges from one to 10 fractions, based on clinician preference and technology available, tumour location and tumour size. This review summarises the safety and efficacy of various SBRT fractionation schedules for HCC.

Optimum Radiation Fractionation Schedule in Advanced Cancer Cervix; A Study from Low Resource North Indian Cancer Center

Introduction: Cervical cancer is the fourth most commonly occurring lethal cancer among women worldwide. The primary curative treatment option for women suffering from locally advanced cervical cancer includes external beam radiotherapy (EBRT) with concurrent weekly platinum-based radiosensitizing chemotherapy and brachytherapy (BT) to obtain finest treatment outcomes. Aim: The purpose of this study is to assess tumor response following HDRBT preceded by EBRT and to identify optimum radiation fractionation schedule for better response with tolerable radiation toxicity. Material and methods: 91 patients diagnosed with carcinoma of uterine cervix were screened for inclusion in the study. Patients were categorized according to FIGO Staging system The patient was put in lithotomy position and given anesthesia and fletcher suit applicator was applied to the patient push the bladder and rectum and finally shifted to the HDR treatment unit. All the associations were tested by using chi square test. Results: In our study it was found that majority (44%) of the cases were aged 51-60 years. Vaginal bleeding and squamous cell carcinoma was found in most of the cases. The acute radiation toxicities were more in elderly age group and the association was found to be statistically significant (p&lt;0.05) except Genitourinary – cystitis. Age group 51-60 years was significantly associated with response (p=0.034) with lower risk of partial response (OR=0.31 (0.10-0.95), while the symptom Backache/Pain in abdomen had significantly higher risk of partial response (p=0.002, OR=16.24 (1.7-154.8). Conclusion: When compared to traditional techniques, HDR can achieve very high rates of local control while lowering morbidity.

Different fractionation schedules of radiotherapy to the primary tumor in metastatic hormone sensitive prostate cancer (Hypo-M1).

TPS192 Background: Radiotherapy of the primary tumor in metastatic prostate cancer is life-prolonging in patients with limited disease spread. Several different fractionation schedules have been used, most widely used is a four-week schedule of 2.75-3 Gy in 19-20 fractions. More data is emerging around hypo-fractionated radiotherapy in the curative setting. We hypothesize that a modified version of the Scandinavian Hypo-trial fractionation 6.1Gy per fraction x 6 fractions over a span of 2½ week will be non-inferior in side-effects as a 4-week schedule but more convenient for patients and caregivers. Methods: The Hypo-M1 trial is a randomized, stratified, multi-center, phase 3 clinical trial recruiting 420 patients in 9 Swedish centers. Key eligibility criteria include histological confirmed prostate cancer, indication for radiotherapy of low burden metastatic prostate cancer, defined as a max of 4 skeletal metastases at any site or lymph node metastases outside the pelvis and no other diseases or treatments interfering with radiotherapy or a score &gt; 20 on the International prostate symptom score (IPSS) scale. Patients will be randomized to either 3 Gy x 19 or 6.1Gy x 6. Stratification factors are T1-T3 vs T4 and randomizing centre. Type of staging procedures performed, CT and whole-body bone scan is recommended, PSMA-PET allowed and further treatment beyond ADT is recorded but not stratification variables. Standard treatment may include docetaxel, apalutamide, abiraterone and enzalutamide at the treating physician’s discretion. Toxicity will be measured before, at the end of radiotherapy and at 1, 3, 6, 12 months and at 3 years. Measures used are the CTCAE v 5.0 and RTOG scales and QoL life will be measured at the same time points with the Prostate Cancer Symptom Scale (PCSS), a validated QoL instrument focusing on prostate cancer radiotherapy. The primary endpoint is QoL at 3 months and key secondary is acute toxicity at 3 months, late toxicity and QoL at 12 months, failure free survival and cause specific survival. The sample size is calculated for a continuous outcome non-inferiority trial with a one-sided alpha-value of 2.5 % and a beta-value of 80 %. The non-inferiority limit is set to 7.5 % This will require 175 patients with complete follow up in each treatment arm. Expecting a response rate of 80 % for the PCSS at the main time end point the total number of patients in each arm will be 210. The National Prostate Cancer Registry, covering 98% of all prostate cancer cases in Sweden, will be used as CRF including also a randomization module, making this a truly population based clinical trial. As of October 12, 2021, accrual is set to begin in December. The Hypo-M1 trial is an investigator-led, academic trial sponsored by the Swedish Society of Urological Oncology with study coordination provided by Cancer Center of Umeå University Hospital, Umeå, Sweden. Clinical trial information: NCT04612907.

Conventional Versus Different Hypofractionated Radiotherapy Dosage Schedules in Postmastectomy Advanced Breast Cancer.

Introduction:The standard treatment for advanced breast cancer is surgery consisting of breast-conserving surgery or modified radical mastectomy (MRM) postneoadjuvant chemotherapy followed by adjuvant radiation treatment (RT). Conventionally-fractionated whole breast irradiation has been the standard RT regimen, but recently shorter courses of hypofractionated whole breast or chest wall irradiation have been advocated for patient convenience and reduction in health-care costs and resources. Radiation is delivered through the same technique, but tumors receive a higher dose of radiation per treatment session with hypofractionation.Aim:The aim of the study was to compare different fractionation schedules of radiotherapy in postoperative cancer breast with respect to locoregional control and toxicities.Materials and Methods:One hundred and eighty-eight patients of cancer breast, who received RT between January 2017 and December 2019 were assessed. Since hypofractionation is well documented and established and being practiced in prestigious institutes, we treated the patients as per their choice to receive 10.15 or 25 fractions. 72 patients (Group A) were treated with conventional fractionation to a dose of 50 Gy/25 fractions/5 weeks. Second group of 62 patients (Group B) were given 40.5 Gy/15 fractions/3 weeks and third group of 54 patients (Group C) were treated with 34 Gy/10 fractions/2 weeks. All patients were T3 or more and underwent MRM after neoadjuvant chemotherapy. They were in the age group of 30–65 years. All of them received adjuvant chemotherapy and hormone therapy in case of estrogen/and progesterone receptor positivity and anti-Her2neu target therapy in case of Her2neu positivity. They were assessed for locoregional control and acute and chronic toxicities.Results:Grade 3 and 4 skin toxicity was similar in all three groups. At 6 months postcompletion of RT, two patients in Group A, 3 in Group B, and 5 in Group C lost to follow-up. In rest of the subjects, there was no locoregional failure. At 1 year, 1 patient from Group A, 2 from Group B, and 1 from Group C developed locoregional recurrence. There were no major chronic toxicities. Arm edema and Telangiectasia were similar in three groups. No rib fracture or major cardiotoxicity and pulmonary toxicity was seen.Conclusion:Hypofractionated RT is a part of the typical treatment regimen for breast cancer nowadays. The major advantage is of convenience to the patients as it is completed the full course of RT in fewer sessions. With both conventional and hypofractionated radiation, the patient receives radiation 5 days a week. In the conventional regimen, though the schedule lasts for 5 weeks, whereas hypofractionation therapy is completed in 2 to 3 weeks. Local control wise both conventional and hypofractionated regimen is similar in locoregional control and toxicity. Therefore, hypofractionated RT should be practiced in cancer breast as it is economical, convenient, and toxicity wise and result wise similar to conventional radiotherapy.

An Evaluation of Pain Response Between Single Fraction Radiotherapy Versus 10 Fractions RT in Metastatic Vertebral Bone Disease: A Quasi Experimental Study

The prognosis of bone metastasis is poor, with median survival measured in months, not years. Treatment remains an important issue to alleviate the complications and sufferings of the patients. This study was aimed to evaluate the pain response between single versus multiple fraction radiotherapy in metastatic vertebral bone disease. In this prospective quasi experimental study, the sample consisted of 60 patients of Oncology Dept., KYAMCH. Purposive sampling method was used. The respondents were divided into 2 arms, Arm A consisted of 30 patients, receiving 800 cGy single fraction RT, and Arm B consisted 30 patients who received 3000 cGy multiple fractions RT. The data were collected using a semi-structured questionnaire, which was constructed in line with the reviewed literature along with RECIST (Response Evaluation in Solid Tumor) criteria, VAS (Visual Analogue Scale) after 4 weeks of RT completion and Radiation Therapy Oncology Group (RTOG) criteria. Mean age of Arm A was 43.73 years, and Arm B was 46.8 years. Lung cancer was the leading cancer in both arms, 43.3% and 36.6% respectively. Adenocarcinoma was the commonest histopathological type of cancer found in both arms, 39.9% and 36.6% respectively. To determine associations, Chi-Square tests were done. For Arm A, 66.6% initially presented with severe pain, 23.31% with moderate and 10% with mild pain. In arm B 59.94%, 33.3% and 6.66% patients presented with severe, moderate and mild pain respectively. One month after completion of RT, pain significantly reduced in patients of both arms with a p value of < .001. No significant difference was observed between 8 Gy in single fraction versus 30 Gy in 10 fractions radiotherapy in the management of secondary bone tumour. It was found, both the radiation fractionation schedule for the management of secondary bone tumour are equally effective. More patients can be provided with the desired treatment with shorter period of time. It will certainly ease the economic burden on the patients as well as on the country.

Radiation Therapy Dose and Fractionation Schedules for Breast Angiosarcomas: An Analysis of the National Cancer Database

Breast angiosarcoma (AS) is an uncommon malignancy that is either secondary to prior radiation therapy (RT) or can occur in the primary setting in the absence of prior RT. Since these malignancies are rare, there are scant prospective data to guide the optimal use and timing of surgery, chemotherapy and RT. Here, we set to focus on details of RT use for primary AS and secondary AS with a focus on the dose, fractionation and timing of RT relative to surgery using the National Cancer Database (NCDB). We hypothesized that RT use would be more frequent in primary AS compared to secondary AS. In addition, we hypothesized that when RT is used, hyperfractionated schedules and preoperative RT would be more common in secondary AS compared to primary AS.We identified patients with a histologic diagnosis of AS from the NCDB from 2004-2016. Patients that were coded as having a prior malignancy were used as a surrogate to denote secondary AS whereas the rest were classified as primary AS. RT use was defined as conventional fractionation (1.8-2.0 Gy/fraction given daily); hypofractionated (> 2.0 Gy/fraction given daily); accelerated hyperfractionated (≤1.5 Gy/fraction given 2-3 times/day); palliative (total dose≤30 Gy); or unknown (insufficient RT details provided). Comparisons between the primary AS and secondary AS groups were performed using the chi-square test with P < 0.05 considered significant.We identified 1,174 patients with non-metastatic AS: 864 secondary AS, 310 primary AS. Radiation was used in 211 patients (18.0%) and was significantly more common in primary AS compared to secondary AS (36.1% [N = 113] vs. 11.4% [N = 98], P < 0.0001). The majority of patients received conventional fractionation (63.5%, N = 134) followed by unknown schedule (16.1%, N = 34), hyperfractionated RT (10.4%, N = 22), palliative RT (6.6%, N = 14), and hypofractionated RT (3.3%, N = 7). Fewer than 10% of patients (N = 18) received preoperative RT but its use was more common in secondary AS vs. primary AS (13.3% vs. 4.4%, P = 0.02). Accelerated hyperfractionated RT use was also more common in secondary AS vs. primary AS (19.4% vs. 2.7%, P < 0.0001). Fractionation schedules for the 22 patients treated with accelerated hyperfractionation included: 1.5 Gy BID to 45-60 Gy in 11 patients; 1.2 Gy BID to 50.4-60 Gy in 8 patients; 1 Gy TID to 45-60 Gy in 3 patients. An additional boost dose of 7.2-15 Gy was given to 11 of these 22 patients.Radiation use for the treatment of breast AS is uncommon, even for patients with primary AS. When RT is used, conventional fractionation schedules predominate. However, accelerated hyperfractionation is used more frequently in secondary AS with 1.5 Gy BID to doses≥45 Gy as the most common regimen. Preoperative RT is rarely used for AS based on this analysis. The under-utilization of RT and wide variations in RT dose/fractionation schedules emphasize the need for more standardized consensus guidelines for this rare but aggressive malignancy.

Patterns of Care in Stereotactic Body Radiation Therapy Fractionation Schedules in Non-Small Cell Lung Cancer in the United States From 2004-2016

Stereotactic Body Radiation Therapy (SBRT) is considered standard of care for inoperable early stage non-small cell lung cancer (NSCLC) and is commonly delivered in 1-5 fractions. Single fraction SBRT is supported by randomized data demonstrating equivalent safety compared to fractionated approaches. The purpose of this study is to measure trends in the utilization of SBRT fractionation in NSCLC patients in the National Cancer Database (NCDB) from 2004-2016.The NCDB was queried for patients with cT1-T3N0M0 NSCLC who were treated with a known SBRT dosing schema during the study period (including 30-34 Gy/1 fraction, 54-60 Gy/3 fractions, 48-50 Gy/4 fractions, and 50-60 Gy/5 fractions). Adjusted logistic regression was used to assess the association of treatment year with the annual percentage of patients who received SBRT using 1, 3, 4, and 5 fractions. Average annual percentage changes (AAPC) were computed and compared to determine if a significant change (defined a priori as P < 0.01) occurred in the use of different fractionation schemes over time. Multivariable analysis was used to evaluate factors associated with receipt of single fraction SBRT.The analytic cohort consisted of 39,536 patients. Use of 3 fraction SBRT decreased from 72.6% in 2004 to 20.3% in 2016 (AAPC -10.6% per year, 95% CI: [-12.1%, -9.1%], P < 0.001). During this interval, a corresponding increase in the use of 5 fraction SBRT also occurred, from 6.5% in 2004 to 53.7% in 2016 (AAPC +18.3% per year, 95% CI: [+13.3%, +23.4%], P < 0.001). No significant change was observed in single fraction and 4 fraction SBRT utilization; < 1% of patients per year received single fraction SBRT in all but three years of the study with a 1.1% percent utilization rate in 2016. On logistic regression, cT2 patients were less likely to receive single fraction SBRT (Odds Ratio 0.592, 95% CI: 0.414-0.846) while academic facility (Odds Ratio 5.821, 95% CI: 4.331-7.823) and Charlson Deyo Score > 2 (Odds Ratio 1.447, 95% CI: 1.038-2.017) were significantly associated with receipt of single fraction SBRT. Age, insurance, distance to treatment facility, and treatment year were not significantly associated with single fraction SBRT.Single fraction SBRT use remained scarce in the United States during 2004-2016, with no clear indication of increased utilization after 2014 when RTOG0915 was first reported. With prospective evidence that long-term toxicity, local control, and survival are similar to 3-4 fraction regimens, the application of single fraction SBRT in the clinic may warrant further interest in light of the recent COVID-19 pandemic and the implementation of the alternative payment model.

Evaluation of the Clinical Outcomes of Altered Fractionated Radiotherapy in Node Positive Breast Cancer (A Retrospective Study)

Abstract Background Hypofractionated radiotherapy schedules provide alternative shorter courses of radiotherapy of more than 2 Gy per fraction and lower total doses compared to the conventionally fractionated schedule of 1.8–2.0 Gy per fraction in 25 fractions. Hypofractionated radiotherapy offers the advantage of improving patients’ convenience and reducing cost and resource requirements. Aim To evaluate the efficacy and toxicity of hypofractionated radiotherapy compared to the conventional schedule. Methods In this retrospective study, the clinical data of 140 patients of node positive breast cancer patients were analyzed. Radiation toxicities and locoregional recurrence were compared between patients who received conventionally fractionated radiation schedule and those who received hypofractionated radiation schedules. Results After a median follow-up of 48 months, the incidence of loco-regional recurrence was comparable between the conventional and hypofractionated arms; 4% vs 3.1%, respectively (P-value = 0.769). Documented acute skin toxicity with ≥ grade 3 was found in 10.6% of the conventional group and in 5.6% of the hypofractionated group (p = 0.409). Grade 1 late lung toxicity was manifested in 6.1% of the conventional group and 7.5% of the hypofractionated group and G2 lung toxicity was found in one case only (1.9%) in the hypofractionated group (p = 0.596). Cardiac toxicity was documented in five cases; 9.4% and 5.1% in the conventional group and hypofractionated groups, respectively (pvalue=0.486). Conclusion Hypofractionated radiotherapy is comparable to conventional radiotherapy regarding locoregional tumor control and treatment toxicities.