Daily Fractions Research Articles

Early Outcomes of Preoperative Short Course Radiotherapy With Simultaneous Integrated Boost and Response-adapted Chemotherapy for Advanced Rectal Cancer

Background and purposeLimited evidence exists for dose escalation in neoadjuvant short course radiotherapy (SCRT) for rectal cancer. With enhanced imaging and radiotherapy techniques over the past decades along with the valuable endpoint of pathological complete response (pCR), we believe SCRT with simultaneous integrated boost could potentially provide deeper pathological responses and improve local control. Methods and MaterialsBetween January 2020 and December 2022, locoregional-advanced rectal cancer patients that were treated with neoadjuvant SCRT with simultaneous integrated boost up to 5.5–6Gy per fraction with five daily fractions followed by response-adapted chemotherapy was retrospectively reviewed. The pCR rates, R0 resection rates, tumor downstaging, toxicities, and early pattern of recurrence are reported. ResultsAmong the 76 patients, 67 (88%) were able to undergo curative intent surgery. R0 resection was achieved in 99% (n = 66) of patients with pCR rates of 28% (n = 19). Forty-six percent (n = 31) of patients had significant pathological downstaging (ypT2N0) and 55% (n = 37) of patients had both T and N downstaging. Most common grade 3 or above radiotherapy-related side-effects were proctitis, rectal pain, and dermatitis found in 5% (n = 4), 3% (n = 2) and 3% (n = 2) of patients, respectively. Grade 3 or above surgical complications were observed in 15% (n = 10) of patients. There were no treatment-related deaths. With a median follow-up of 27 months, only 6% (n = 4) had local recurrence after surgery. ConclusionsNeoadjuvant short course radiotherapy with simultaneous boost for rectal cancer is feasible with no added toxicities. Patients who underwent surgery achieve a high R0 resection and pCR rates. Early data suggest low rates of locoregional recurrence. Further follow-up and research is needed to validate and optimize the dose, method, and schedule of dose escalation.

In vivo dosimetry of total body irradiation patients: A 10 year retrospective analysis

Myeloablative Total Body Irradiation (TBI) used in our Institution, as part of the conditioning scheme for haematopoietic stem cell transplantation, is an extended-distance supine technique that has been implemented using a 15 MV LINAC beam, lead lung compensators, PMMA, and water bolus to improve homogeneity. This study reviews in-vivo dosimetry (IVD) over 10 years of treatments, assessing the technique’s robustness, accuracy, and efficiency.A 2-lateral opposite fields plan was calculated from planning CT with validated Oncentra TPS (Elekta AB, Sweden). Monitor units (MUs), lung compensators shape and thickness were calculated to deliver the prescription dose (12 Gy in 6 bi-daily fractions or 9.9 Gy in 3 daily fractions) to the patient’s abdomen midline at the umbilical level, maintaining lung dose within ±5 % range of prescription. Data from 103 patients, of which more than 87 % were pediatric, were retrieved and analyzed for a total of 537 treatment fractions. The impact of IVD omission was evaluated, supposing doing it only once or in the first two fractions, if necessary.Median ΔMU from planned was −1.2 %. Median percentage dose deviation from prescription in 6 anatomical regions was below 2 %. IVD omission could have resulted in an increase of 7 patients registering at least one anatomical region outside the ±5 % dose range at the end of treatment.It is possible to confirm the implemented technique’s robustness and accuracy in delivering the prescribed dose under IVD monitoring. Nevertheless, this technique and associated IVD are time-consuming and IVD omission could be assessed with limited drawbacks.

Accelerated Partial Breast Irradiation for Early-Stage Invasive Lobular Carcinoma

Purpose: Invasive lobular carcinoma (ILC) represents 10-15% of invasive breast cancers with limited representation among trials of accelerated partial breast irradiation (APBI). Contemporary guidelines advise against treating ILC with APBI given a paucity of supportive evidence. Here, we evaluated oncologic outcomes among patients with ILC treated with APBI. Methods: Patients treated from 2010 –2022 with APBI following breast conserving surgery for ILC (or mixed ILC with other histologies) were ascertained from a prospectively-maintained institutional database. All patients received external beam APBI to 40Gy in 10 daily fractions. Outcomes of interest included local recurrence (LR) and overall survival (OS). Results: Of 1248 patients who underwent APBI at our center, the study cohort comprised 132 (11%) who had ILC, either exclusively or mixed with another histology (median age 63). Median tumor size was 1.1cm (IQR: 0.8, 1.5), nearly all had estrogen receptor positive disease (99%) and received endocrine therapy (91%), and most underwent sentinel node biopsy (89%) with the remainder having no axillary surgery. At 530 person-years and a median follow-up of 39 months, two LRs were observed yielding a 48-month cumulative incidence of LR of 3.0% (95% CI 0.56 –9.5%). Both events arose in patients with mixed lobular histology (none arose in patients with pure ILC). Two unrelated deaths were also observed yielding a 48-month overall survival of 98% (95% CI: 95% - 100%) Conclusion: Among patients with ILC who received APBI following BCS, we observed a 4-year LR rate of 3%. No regional or distant recurrences were observed, and overall survival was excellent. The safety of APBI for ILC will require confirmation among larger trials with longer follow-up, although the excellent outcomes observed here are consistent with those seen for invasive ductal carcinomas among contemporary trials of APBI.

A Phase 1 Trial of Image Guided Risk Volume-Adapted Postprostatectomy Radiation Therapy

This was a phase 1 trial with the primary objective of identifying the most compressed dose schedule (DS) tolerable using risk volume-adapted, hypofractionated, postoperative radiation therapy (PORT) for biochemically recurrent prostate cancer. Secondary endpoints included biochemical progression-free survival and quality of life (QOL). Patients were treated with 1 of 3 isoeffective DSs (DS1: 20 fractions, DS2: 15 fractions, and DS3: 10 fractions) that escalated the dose to the imaging-defined local recurrence (73 Gy3 equivalent dose in 2Gy fractions) and de-escalated the dose to the remainder of the prostate bed (48 Gy3 equivalent dose in 2Gy fractions). Escalation followed a standard 3 + 3 design with a 6-patient expansion at the maximally tolerated hypofractionated DS. Dose-limiting toxicity was defined as Common Terminology Criteria for Adverse Events v.4.0 grade (G) 3 toxicity lasting >4 days within 21 days of PORT completion or G4 gastrointestinal (GI) or genitourinary toxicities thereafter. QOL was assessed longitudinally through 24 months with the Expanded Prostate Cancer Index Composite short form. Between January 2018 and December 2023, 15 patients were treated (3 with DS1, 3 with DS2, and 9 with DS3). The median follow-up was 48 months. No dose-limiting toxicities were observed on any DS, and thus, expansion occurred at DS3. The cumulative incidence of G3 GI and genitourinary toxicity was 7% and 9% at 24 months, respectively, with no G4 events observed. Transient, acute G2+ GI toxicity was the most common. QOL worsened transiently during study follow-up in urinary incontinence, GI, and sexual subdomains but was similar to baseline by 24 months. The biochemical progression-free survival was 91% at both 24 and 60 months. The maximally tolerated hypofractionated DS for hypofractionated, risk volume-adapted PORT was determined to be DS3 (36.4 Gy to the prostate bed and 47.1 Gy to the imaging-defined recurrence in 10 daily fractions). No >G3 events were observed. Transient declines in QOL did not persist through 24 months.

Automated detection of regions with persistently enhanced methane concentrations using Sentinel-5 Precursor satellite data

Abstract. Methane (CH4) is an important anthropogenic greenhouse gas, and its rising concentration in the atmosphere contributes significantly to global warming. A comparatively small number of highly emitting persistent methane sources are responsible for a large share of global methane emissions. The identification and quantification of these sources, which often show large uncertainties regarding their emissions or locations, are important to support mitigating climate change. Daily global column-averaged dry air mole fractions of atmospheric methane (XCH4) are retrieved from radiance measurements of the TROPOspheric Monitoring Instrument (TROPOMI) on board on the Sentinel-5 Precursor (S5P) satellite with a moderately high spatial resolution, enabling the detection and quantification of localized methane sources. We developed a fully automated algorithm to detect regions with persistent methane enhancement and to quantify their emissions using a monthly TROPOMI XCH4 dataset from the years 2018–2021. We detect 217 potential persistent source regions (PPSRs), which account for approximately 20 % of the total bottom-up emissions. By comparing the PPSRs in a spatial analysis with anthropogenic and natural emission databases, we conclude that 7.8 % of the detected source regions are dominated by coal, 7.8 % by oil and gas, 30.4 % by other anthropogenic sources like landfills or agriculture, 7.3 % by wetlands, and 46.5 % by unknown sources. Many of the identified PPSRs are in well-known source regions, like the Permian Basin in the USA, which is a large production area for oil and gas; the Bowen Basin coal mining area in Australia; or the Pantanal Wetlands in Brazil. We perform a detailed analysis of the PPSRs with the 10 highest emission estimates, including the Sudd Wetland in South Sudan, an oil- and gas-dominated area on the west coast in Turkmenistan, and one of the largest coal production areas in the world, the Kuznetsk Basin in Russia. The calculated emission estimates of these source regions are in agreement within the uncertainties in results from other studies but are in most of the cases higher than the emissions reported by emission databases. We demonstrate that our algorithm is able to automatically detect and quantify persistent localized methane sources of different source type and shape, including larger-scale enhancements such as wetlands or extensive oil- and gas-production basins.

Is intensive training with atime interval between instruction and planning CT necessary for deep inspiration breath-hold radiotherapy in breast cancer?

Breathing instruction and exercises and atime gap between training and planning CT scans (pCT) is recommended as part of deep inspiration breath-hold (DIBH) assisted radiotherapy (RT). However, this is associated with additional time expenditure. In two of the authors' treatment centers (TC), patient training took place before the planning CT of DIBH-assisted therapy. In TC1, afurther appointment was made with aminimum interval of 2days to perform the planning CT. At TC2, the planning CT was performed immediately after the first patient instruction. Aretrospective evaluation of the clinical parameters of the therapy was carried out to investigate the relevance of the time gap between DIBH exercises and pCT. Atotal of 72patients were included, 35 of whom were treated in TC1 and37 in TC2. In TC1, an average interval of ~4 days was observed between patient training and planning CT, while in TC2, training and CT were performed immediately after each other. No significant differences in radiation dose exposure of the lung on the treated side, the whole lung, or the heart were found between the two centers. Furthermore, there was no significant difference in the application of the daily RT fraction. The requirement for daily positioning checks was also the same at both treatment centers. This study does not show any advantages for atime gap between instruction/training and pCT. Skipping the time break does not deteriorate any clinically relevant endpoints.

Estimation of daily XCO2 at 1 km resolution in China using a spatiotemporal ResNet model

Carbon dioxide (CO2) serves as a crucial greenhouse gas that traps heat and regulates the Earth's temperature. High spatiotemporal resolution CO2 estimation can provide valuable information to understand the characteristics of fine-scale climate change trends and to formulate more effective emission reduction strategies. This study presents a spatiotemporal ResNet model (ST-ResNet) specifically developed to estimate the highest resolution (1 km × 1 km) daily column-averaged dry-air mole fraction of CO2 (XCO2) in China from 2015 to 2020. The ST-ResNet model excels in estimating XCO2 by comprehensively considering the complex relationships between XCO2 and its various influencing factors, while efficiently capturing both temporal and spatial correlations, thereby demonstrating remarkable generalization capability. The results show that the ST-ResNet generates a highly accurate XCO2 dataset, outperforming the traditional ResNet. Ground-based validation results further confirm the high accuracy and spatiotemporal resolution of our estimated data product. Using this dataset, the spatial and temporal characteristics of XCO2 across the entire China and several urban agglomerations have been analyzed. The high spatiotemporal resolution estimated XCO2 dataset for China is made publicly available at [https://doi.org/10.6084/m9.figshare.25272868], offering substantial potential for fine-scale carbon research.

Comparative Study on Symptomatic Response and Toxicity of Concurrent Chemo-Radiotherapy and Radiotherapy Alone in the Treatment of Cervical Cancer

This prospective observational study was carried out to compare the symptomatic response and acceptable toxicity in concurrent chemo-radiotherapy and radiotherapy alone in the treatment of cervical cancer. A total of 60 patients (30 patients in arm A & 30 patients in arm B) who have biopsy proven cervical carcinoma with no history of previous treatment were selected from the Department of radiotherapy Rajshahi Medical College Hospital, Rajshahi & in the department of Radiation & Oncology, National Institute of Cancer Research & Hospital. All patients in both arms received external beam radiation with 50Gy in 25 daily fractions over five weeks. Followed by three insertions (one insertion per week) of Intracavitary brachytherapy each 700 cGy. Patients in arm-A received Inj. Cisplatin 40mg/m2 in IV infusion on the first day of each treatment per week in addition to radiotherapy. In this study it was observed that a significant symptomatic improvement was found in arm-A after treatment than arm-B and no severe unwanted reaction was noted in most of the patients. Systematic toxicity developed in both groups and comparatively more in arm-A (chemo radiation) but that was not statistically significant and well managed with conservative treatment. Regarding performance status patients treated with concurrent chemo radiation showed better performance status than the patient treated with radiotherapy alone. In this study it was observed that patients of carcinoma cervix treated with concurrent chemo radiotherapy was effective for symptomatic improvement and feasible with acceptable toxicity for advanced cancer of the uterine cervix than those with radiation alone.

RRx-001 Affects Multiple Toxicities in Patients Receiving Concomitant Chemoradiation for Head and Neck Cancers: Observations of the PREVLAR Phase II Trial

PURPOSE Phase IIa trial results suggested that RRx-001, an nucleotide-binding domain-like receptor protein 3 inhibitor and nuclear factor erythroid 2–related factor 2 activator, attenuated severe oral mucositis (SOM) in patients treated with concomitant chemoradiation (CRT) for oral cancer (OC) and oropharyngeal cancer (OPC). Given the shared pathobiology of CRT injury among other exposed tissues, we initiated a secondary analysis of reported adverse events (AEs) to assess RRx-001's potential benefit on non-SOM regimen-related toxicities. METHODS PREVLAR was an open-label randomized trial that has been completed and published. Patients were treated with CRT for locally advanced OC or OPC. Arms 1-3 received doses of RRx-001 twice a week beginning 2 weeks before the start of CRT. Arm 2 (n = 11) received additional RRx-001 once during weeks 2 and 5. Arm 3 (n = 13) received RRx-001 once a week for the first 6 weeks of CRT. Arm 4 (n = 10) received CRT only. Patients received standard intensity modulated radiation therapy (daily fractions of 2-2.2 Gy/minimum cumulative dose of 55 Gy) plus cisplatin. Comprehensive toxicity assessment was based on reported AEs graded using Common Terminology Criteria for Adverse Events v5.0 and categorized with the Medical Dictionary for Regulatory Activities. A two-sided Fisher's exact test was performed to compare AE incidences between RRx-001 arms and standard of care in a secondary analysis of the data. Overall false-positive rate in Fisher's exact test was controlled via Hochberg's adjustment method. RESULTS Compared with the control cohort, patients receiving RRx-001 demonstrated fewer AEs attributable to their CRT regimen. Statistically significant differences in AE incidences favoring RRx-001 were dependent on the RRx-001 dosing regimen. CONCLUSION This secondary analysis suggests that RRx-001 infusion may reduce multiple, biologically related AEs associated with a standard CRT regimen. More broadly, it suggests that it is possible that agents that effectively target central pathobiology targets may mitigate more than one toxicity.

Comparison between Trans-Arterial Chemoembolization Followed by Stereotactic Body Radiation Therapy and Trans-Arterial Chemoembolization Alone in BCLC Stage B Hepatocellular Carcinoma: A Pilot Study.

Both Stereotactic Body Radiation Therapy (SBRT) and Trans-arterial Chemoembolization (TACE) are now being widely used to treat advanced hepatocellular carcinoma (HCC) and can improve tumor local control rates. We aimed at evaluating the efficacy and toxicity of combining SBRT and TACE in comparison to TACE alone in unresectable HCC. 42 unresectable Barcelona Clinic Liver Cancer (BCLC) stage B HCC Child Pugh (CP) A patients were randomized to receive either: TACE alone (Arm A) or TACE followed by SBRT (Arm B). Dose prescribed was 40Gy in 5consecutive daily fractions over 1 week . We compared the local control (LC), Progression free survival (PFS), overall survival (OS) and toxicity between the two arms. 22 patients were in arm A versus 20 patients in arm B with median follow up 20 months starting recruitment from April 2021 till January 2023. Both LC, PFS were significantly better in Arm B. Complete remission (CR) rate was 54.5% and 75% in Arm A and B, respectively. Median PFS was 16 months in Arm B compared to 11 months in Arm A (p =0.003). Median OS was not reached in both arms. Both arms had comparable toxicities. Adding SBRT to TACE in advanced HCC, is safe and feasible with better efficacy in terms of LC and PFS with comparable side effects, in comparison to TACE alone.

Evaluating a hypofractionated radiotherapy schedule for prostate cancer at an institution in South Africa

Background: Hypofractionated radiotherapy (HFRT) in the treatment of prostate cancer (PCa) has logistical and cost advantages, especially in a resource constrained setting. Studies have demonstrated equivalent efficacy with HFRT schedules using Intensity Modulated Radiation Therapy (IMRT) as treatment modality. However, higher rates of acute and late gastrointestinal (GI) and genitourinary (GU) toxicity have been reported when compared to conventionally fractionated radiotherapy (CFRT). In this study, we evaluate the efficacy and toxicity rates of a HFRT schedule using 3D conformal radiotherapy (RT) as treatment modality.Aim: With this study, we aim to describe the safety and outcomes of a definitive HFRT schedule used for localised PCa. We hypothesise that there is no difference in the biochemical relapse rate and incidence rates of normal tissue toxicities between patients receiving CFRT and HFRT schedules.Setting: This RT schedule was used at Tygerberg Academic Hospital in South Africa for the treatment of localised prostate cancer.Methods: This is a retrospective study in which the records of patients diagnosed with localised PCa were reviewed. Patients were treated with either CFRT regimen to a total of 74Gy in 37 daily fractions for 5 days a week or a HFRT regimen to a total of 65Gy in 26 daily fractions for 4 days per week.Results: In all, 116 patients were included in the study with a median follow-up of 57.2 months from the start of RT. No statistically significant differences in overall survival (OS) and biochemical relapse-free survival were found between the two schedules. A significant difference in acute GI toxicity was observed, with a higher incidence noted in the HFRT schedule. No significant differences were observed in late GI toxicity or in early and late GU toxicities.Conclusion: This study observes a hypofractionated regimen using three-dimensional conformal radiation therapy (3DCRT) with similar efficacy and RT-related toxicities to CFRT.Contribution: The HFRT schedule used in this study could be useful in hospitals with limited access to resources.

Association of increasing gross tumor volume dose with tumor volume reduction and local control in fractionated stereotactic radiosurgery for unresected brain metastases

BackgroundFractionated stereotactic radiosurgery (fSRS) is an important treatment strategy for unresected brain metastases. We previously reported that a good volumetric response 6 months after fSRS can be the first step for local control. Few studies have reported the association between gross tumor volume (GTV) dose, volumetric response, and local control in patients treated with the same number of fractions. Therefore, in this study, we aimed to investigate the GTV dose and volumetric response 6 months after fSRS in five daily fractions and identify the predictive GTV dose for local failure (LF) for unresected brain metastasis.MethodsThis retrospective study included 115 patients with 241 unresected brain metastases treated using fSRS in five daily fractions at our hospital between January 2013 and April 2022. The median prescription dose was 35 Gy (range, 30–35 Gy) in five fractions. The median follow-up time after fSRS was 16 months (range, 7–66 months).ResultsGTV D80 > 42 Gy and GTV D98 > 39 Gy were prognostic factors for over 65% volume reduction (odds ratio, 3.68, p < 0.01; odds ratio, 4.68, p < 0.01, respectively). GTV D80 > 42 Gy was also a prognostic factor for LF (hazard ratio, 0.37; p = 0.01).ConclusionsGTV D80 > 42 Gy in five fractions led to better volume reduction and local control. The goal of planning an inhomogeneous dose distribution for fSRS in brain metastases may be to increase the GTV D80 and GTV D98. Further studies on inhomogeneous dose distributions are required.

Stereotactic radiotherapy for liver oligometastases: a pooled analysis following the estro/eortc consensus recommendations.

A large pooled analysis of liver oligometastases, classified accordingly to the ESTRO/EORTC recommendations, treated by stereotactic radiotherapy (SBRT) and Radiosurgery (SRS) was carried out. The clinical and dosimetric data of patients who underwent SBRT/SRS for liver metastases were analysed in terms of efficacy and toxicity profile. In particular, the Local Control (LC), the Distant Metastases Free Survival (DMFS), the Disease-Free Survival (DFS), the Overall Survival (OS), and the Next Systemic Therapy Free Survival (NEST-FS) rates were analysed. 113 patients (M/F: 49/64), accounting for a total of 150 hepatic lesions (March 2006-February 2023) in two Italian radiotherapy Institutions were evaluated. Median age was 67years old (36-92) and 48 (42.5%) patients had at least one comorbidity. The majority of the lesions were induced (30.7%) or repeated oligoprogressive (12.7%) metastases. 98 lesions were treated with more than one daily fraction (mainly 50Gy in 5 fractions), while 52 were radiosurgery treatments (mainly 32Gy). The treatment response at 3-4months was evaluable in 147 lesions: complete response was 32.0%, partial response 17.0%, and stable disease 32.0%. Actuarial LC, DMFS, DFS, OS, and NEST-FS at 1 year were 75.8%, 37.7%, 34.9%, 78.7%, and 59.4% respectively; while actuarial LC, DMFS, DFS, OS, and NEST-FS at 2 years were 52.1%, 24.9%, 21.9%, 51.3%, and 36.8%, respectively. The achievement of complete response, synchronous oligometastases, and no treatment interruptions correlated with a more favorable outcomes. As per the toxicity profile, we registered only two acute and one late toxicity cases higher than grade 2. Stereotactic treatment for liver metastases seems to be a safe and promising option in terms of local control. The best results in term of outcomes have been obtained in patients with complete response, synchronous oligometastases, favorable histology, and no treatment interruptions.

Ultrahypofractionation in postoperative radiotherapy for breast cancer: A single-institution retrospective cohort series.

The 'FAST-forward', study published in April 2020, demonstrated the effectiveness of an extremely hypofractionated radiotherapy schedule, delivering the total radiation dose in five sessions over the course of 1 week. We share our department's experience regarding patients treated with this regimen in real-world clinical settings, detailing outcomes related to short-term toxicity and efficacy. A descriptive observational study was conducted on 160 patients diagnosed with breast cancer. Between July 2020 and December 2021, patients underwent conservative surgery followed by a regimen of 26 Gy administered in five daily fractions. The median age was 64 years (range: 43-83), with 82 patients (51.3%) treated for left-sided breast cancer, 77 patients (48.1%) for right-sided breast cancer, and 1 instance (0.6%) of bilateral breast cancer. Of these, 66 patients had pT1c (41.3%), 70.6% were infiltrative ductal carcinomas, and 11.3% were ductal carcinoma insitu. Most tumours exhibited intermediate grade (41.9%), were hormone receptor positive (81.3%), had low Ki-67 (Ki-67 < 20%; 51.9%) and were Her 2 negative (85%). The majority of surgical margins were negative (99.4%). Among the patients, 72.5% received hormonotherapy, and 23.8% received chemotherapy. Additionally, 26 patients (16.3%) received an additional tumour boost following whole breast irradiation (WHBI) of 10 Gy administered in five sessions of 2 Gy over a week. The median planning target volume (PTV) was 899 cm3 (range: 110-2509 cm3). Early toxicity was primarily grade I radiodermatitis, affecting 117 patients (73.1%). During a median follow-up of 15 months (range: 3.9-28.77), only one patient experienced a local relapse, which required mastectomy. The implementation of this highly hypofractionated regimen in early-stage breast cancer appears feasible and demonstrates minimal early toxicity. However, a more extended follow-up duration would be required to evaluate long-term toxicity and efficacy accurately.

Outcomes of Stereotactic Radiation Therapy Versus Fractionated Radiation Therapy in 44 Dogs With Pituitary Masses: A Multi-Institutional Retrospective Study (2016-2022).

Although canine pituitary masses (PM) are increasingly treated with stereotactic radiotherapy (SRT), historical literature supports superior outcomes with conventional full-course fractionated radiation therapy (FRT). A multi-institutional retrospective study was performed, including dogs with PM treated from 2016 to 2022 with SRT (total dose 30 or 35 Gy in 5 daily fractions) or FRT (total dose 50-54 Gy in 19-20 daily fractions). The influence of potential prognostic/predictive factors was assessed, including pituitary: brain height, pituitary: brain volume, sex, age and endocrine status (functional [F] vs. nonfunctional [NF] PM). Forty-four dogs with PM were included (26 F, 14 NF, 4 unknown). All patients completed protocols as scheduled (SRT = 27, FRT = 17) and two dogs had suspected Grade 1 acute neurotoxicity. During the first 6 months after RT, 5/27 (19%) dogs treated with SRT (4 F, 1 NF) and 3/17 (18%) dogs treated with FRT (all F) died or were euthanised because of progressive neurologic signs. The overall median survival time was 608 days (95% CI, 375-840 days). Young age at the time of treatment was significant for survival (p = 0.0288); the overall median survival time was 753 days for dogs <9 years of age (95% CI, 614-892 days) and 445 days for dogs ≥9 years of age (95% CI, 183-707 days). Survival time was not associated with treatment type or any other factor assessed herein. A prospective study using standardised protocols would further validate the results of the present study and potentially elucidate the predictors of early death.

A randomized phase II trial of atezolizumab with or without tiragolumab before and after definitive chemoradiation for unresectable stage III non-small cell lung cancer (NSCLC; AFT-57).

TPS8123 Background: A minority of patients with unresectable stage III non-small cell lung cancer (NSCLC) may be cured by chemoradiotherapy (CRT). Adjuvant checkpoint inhibition through PD-L1 blockade after CRT improved survival compared to placebo in the PACIFIC trial (median progression-free survival (mPFS) 16.9 vs 5.6 months (mo), median overall survival (mOS) 47.5 vs 29.1 mo), but overall survival at 5 years remains below 50% (Spigel D, et al J Clin Oncol 2022, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9015199/ . Only patients completing CRT without progression and with good performance status were eligible for this approach. Neoadjuvant checkpoint inhibition would allow more patients the opportunity to benefit from immunotherapy and may attenuate tumor-related immunosuppression via depletion of regulatory T cells and clonal expansion of effector T cells, thereby improving tumor immunogenicity. Neoadjuvant atezolizumab had favorable outcomes compared to historic PACIFIC data in the phase II single arm trial, AFT-16 (mPFS 30 mo and mOS not reached). Whether combination immunotherapy therapy before CRT will improve outcomes in this setting is the question posed in the AFT-57 trial. Methods: This phase II randomized Alliance Foundation Trials study (AFT-57) will evaluate safety and efficacy of atezolizumab with or without the anti-TIGIT monoclonal antibody, tiragolumab, before and after definitive CRT with concurrent atezolizumab. The primary endpoint is PFS in the two experimental arms with a goal to select the most promising regimen for further study. AFT-57 will randomly assign 158 patients with stage III NSCLC (AJCC v8), Eastern Cooperative Oncology Group performance status 0-1, no active autoimmune disease and no underlying organ dysfunction to 2 cycles of neoadjuvant atezolizumab (1200 mg intravenously [IV] every 21 days) with or without tiragolumab (600 mg IV). Non-progressing patients will receive carboplatin and paclitaxel weekly with atezolizumab 1200 mg IV every 21 days concurrent with 60 Gray involved field thoracic radiation in 30 daily fractions (Monday - Friday) followed by atezolizumab with or without tiragolumab on the same schedule as the neoadjuvant doses, with a plan to complete one year of therapy. A pilot cohort of 20 patients for whom tiragolumab will be combined with atezolizumab during chemoradiotherapy is planned toward the end of accrual. Correlative science includes tissue and blood-based immune-related biomarkers at baseline and during therapy. This trial utilizes the Alliance Participant Engagement Portal, a patient-facing site designed to provide information and resources to Alliance clinical trial participants. The trial was activated on 12/7/23 with the first patient screened 1/19/24. Clinical trial information: NCT05798663 .

A preliminary investigation of a novel solar-powered absorption-desiccant-radiant cooling system for thermally active buildings

Desiccant air-conditioning systems are considered a competitive alternative to conventional vapor compression cycles. However, the literature lacks detailed studies of such systems when coupled with thermally active buildings and powered by solar energy due to the complexity of modeling and controlling the system. In the present study, a novel hybrid desiccant-dehumidification-absorption system, driven by external compound parabolic concentrators (DDA-XCPC), is used to serve a typical office space in a hot climate zone. The entire system is modeled and simulated dynamically in the TRNSYS environment. The current study investigates the proposed system performance in terms of the achieved thermal comfort, energy consumption, solar fraction, life cycle costs, and carbon emissions. The results reveal superior thermal comfort levels with percentages of people dissatisfied below 5.6 %. The daily solar fraction ranged between 41 and 90 %, with an average of 49 %, whereas the coefficient of performance varied between 0.46 and 1.38 while having a season average of 0.86. Compared to a conventional system, driven by a gas boiler, the proposed system increased the life cycle costs by 6,824 USD due to the large capital investment of the solar thermal loop. However, each 1,000 USD of additional expenses was accompanied by a cutdown of 4,619 kg of CO2 emissions. Increments in the solar system’s capacity (i.e., solar collector area and storage tank volume) have adverse and favorable impacts on the economic and environmental performances, respectively. Therefore, the system can be a viable option whenever green energy production is prioritized and considerably incentivized.

Intensity-Modulated Reirradiation Therapy With Nivolumab in Recurrent or Second Primary Head and Neck Squamous Cell Carcinoma

Intensity-modulated radiation therapy (IMRT) reirradiation of nonmetastatic recurrent or second primary head and neck squamous cell carcinoma (HNSCC) results in poor progression-free survival (PFS) and overall survival (OS). To investigate the tolerability, PFS, OS, and patient-reported outcomes with nivolumab (approved standard of care for patients with HNSCC) during and after IMRT reirradiation. In this multicenter nonrandomized phase 2 single-arm trial, the treatment outcomes of patients with recurrent or second primary HNSCC who satisfied recursive partitioning analysis class 1 and 2 definitions were evaluated. Between July 11, 2018, and August 12, 2021, 62 patients were consented and screened. Data were evaluated between June and December 2023. Sixty- to 66-Gy IMRT in 30 to 33 daily fractions over 6 to 6.5 weeks with nivolumab, 240 mg, intravenously 2 weeks prior and every 2 weeks for 5 cycles during IMRT, then nivolumab, 480 mg, intravenously every 4 weeks for a total nivolumab duration of 52 weeks. The primary end point was PFS. Secondary end points included OS, incidence, and types of toxic effects, including long-term treatment-related toxic effects, patient-reported outcomes, and correlatives of tissue and blood biomarkers. A total of 62 patients were screened, and 51 were evaluable (median [range] age was 62 [56-67] years; 42 [82%] were male; 6 [12%] had p16+ disease; 38 [75%] had salvage surgery; and 36 [71%.] had neck dissection). With a median follow-up of 24.5 months (95% CI, 19.0-25.0), the estimated 1-year PFS was 61.7% (95% CI, 49.2%-77.4%), rejecting the null hypothesis of 1-year PFS rate of less than 43.8% with 1-arm log-rank test P = .002 within a 1-year timeframe. The most common treatment-related grade 3 or higher adverse event (6 [12%]) was lymphopenia with 2 patients (4%) and 1 patient each (2%) exhibiting colitis, diarrhea, myositis, nausea, mucositis, and myasthenia gravis. Functional Assessment of Cancer Therapy-General and Functional Assessment of Cancer Therapy-Head and Neck Questionnaire quality of life scores remained stable and consistent across all time points. A hypothesis-generating trend favoring worsening PFS and OS in patients with an increase in blood PD1+, KI67+, and CD4+ T cells was observed. This multicenter nonrandomized phase 2 trial of IMRT reirradiation therapy and nivolumab suggested a promising improvement in PFS over historical controls. The treatment was well tolerated and deserves further evaluation. ClinicalTrials.gov Identifier: NCT03521570.

Abstract PO5-22-02: Evaluation of a surface-guided and tattoo-less approach to setup for whole breast radiotherapy

Abstract Background: In preparation for adjuvant breast radiation therapy (RT), several small but permanent skin tattoo marks are often placed to assist with surface alignment for treatment setup and delivery. With advancements in surface-guided technologies, it may be possible to achieve setup accuracy with a “tattoo-less” approach, which can improve cosmetic and quality of life outcomes. This study evaluates the feasibility, accuracy, and potential dosimetric implications of a tattoo-less setup technique. Method: A retrospective analysis of 10 patients diagnosed with right-sided breast cancer who received adjuvant whole breast RT using a tattoo-less approach were included in this study. All patients received an initial whole breast dose of 42.56 Gray (Gy) in 16 daily fractions using a tangential three-dimensional conformal planning technique. This was followed by a 10Gy boost to the lumpectomy site delivered in 4 daily fractions. Daily setup for whole breast treatment was performed by aligning each patient to their individual reference breast surface generated from the planning computed tomography (CT) images via the Vision RT system. Bony landmarks were then verified via daily kV imaging, and translational shifts were recorded for each fraction. The kV imaging was performed to confirm the treatment positioning since the tattoo-less approach was new to the department. For 5 patients, dosimetric differences between initial surface alignment and shifts performed based on bony landmarks were evaluated by recalculating the original clinical plan with a new isocenter position using kV image shifts for each of their 16 treatment fractions. A plan sum of the 16 recalculated plans for each patient was used in further dosimetric analysis. Boost fractions were not included in this study, as setup was verified using surgical clips instead of bony anatomy. Results: Translational shifts for 158 fractions were reviewed as no kV imaging was performed for the other 2 fractions. The mean absolute kV imaging shift was 0.29 cm (CI (95%): 0.25, 0.32; range: 0 to 1.25) in the vertical axis, 0.28 cm (0.23, 0.32; 0 to 1.27) in the longitudinal axis, and 0.24 cm (0.20, 0.28; 0 to 1.98) in the lateral axis. Clinical plans for 5 patients were evaluated with a mean absolute kV shift of 0.27 cm (range: 0.15 to 0.39) in the vertical, 0.32 cm (0.13 to 0.77) in the longitudinal, and 0.29 cm (0.18 to 0.38) in the lateral directions. Dosimetric analysis revealed a slight increase in mean heart dose from the original clinical plan, with an average difference of 4.12 cGy (range: 0.7 to 10.5 cGy). The maximum increase in V20Gy of the ipsilateral lung was 2.7%. Less than 1% of change was observed in the maximum plan dose, as well as in the V95% coverage, expect for one patient, whose V95% was decreased from 99.6% to 94.6%. This difference was caused by a large longitudinal shift which could be attributed to possible patient movement. Conclusions: These findings demonstrate the feasibility and accuracy of a tattoo-less treatment approach in a small cohort of breast cancer patients receiving whole breast RT. Further investigation with larger cohorts is warranted. Citation Format: Xinxin Zhang, Swati Mamidanna, Yin Zhang, Xiao Wang, Ning Yue, Shicha Kumar, Lindsay Potdevin, Maria Kowzun, Mridula George, Lara Hathout, Bruce Haffty, Nisha Ohri. Evaluation of a surface-guided and tattoo-less approach to setup for whole breast radiotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-22-02.

Assessing the Impact of Climate Change on Snowfall Conditions in Poland Based on the Snow Fraction Sensitivity Index

This study focuses on temperature and snowfall conditions in Poland, both of which were analyzed from 1981 to 2020. A 40-year record of daily snow fraction time series values was reconstructed using a unique and global multi-source weighted-ensemble precipitation (MSWEP) product, which provided a spatially and temporally consistent reference for the assessment of meteorological conditions. The average states and trends in snow fraction and temperature were analyzed across several years, focusing on the 6-month cold season (November–April). The impact of temperature on the snow fraction pattern was assessed by introducing a snow fraction sensitivity index. To predict short-term changes in snow conditions, a proxy model was established; it incorporated historical trends in the snow fraction as well as its mean state. This study provides clear evidence that the snow fraction is principally controlled by increases in temperature. A warming climate will thus cause a decline in the snow fraction, as we observed in vast lowland areas. Given the ongoing global warming, by the 2050s, snow-dominated areas may go from covering 86% to only 30% of the country’s surface; they will be converted into transient rain–snow areas. Our results demonstrate that a decline in snow water resources has already occurred, and these resources are expected to diminish further in the near future. New insights into the sensitivity of the snow fraction to climate warming will expand our collective knowledge of the magnitude and spatial extent of snow degradation. Such widespread changes have implications for the timing and availability of soil and groundwater resources as well as the timing and likelihood of floods and droughts. Thus, these findings will provide valuable information that can inform environmental managers of the importance of changing snowfall conditions, guiding them to include this aspect in future climate adaptation strategies.