Abstract: Background: Cancer-associated fibroblasts (CAFs) are a diverse subset of cells, that is recently gaining in popularity and have the potential to become a new target for breast cancer therapy; however, broader research is required to understand their mechanisms and interactions with breast cancer cells. The goal of the study was to isolate CAFs from breast cancer tumour and characterise isolated cell lines. We concentrated on numerous CAF biomarkers that would enable their differentiation. Materials and methods: Flow cytometry, immunofluorescence, and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) were used to phenotype the primary CAFs. Results/Conclusions: According to our findings, there was no significant pattern in the classification of cancer-associated fibroblasts. The results of biomarkers expression were heterogeneous, thus no specific subtypes were identified. Furthermore, a comparison of cancer-associated fibroblasts derived from different BC subtypes (luminal A and B, triple-negative, HER2 positive) did not reveal any clear trend of expression.

Abstract: The focus of this paper was to review and summarise the current issues and recent trends within the framework of locally advanced (LA) non-small cell lung cancer (NSCLC). The recently proposed 8 th tumour–node–metastases (TNM) staging system exhibited significant amendments in the distribution of the T and M descriptors. Every revision to the TNM classification should contribute to clinical improvement. This is particularly necessary regarding LA NSCLC stratification, therapy and outcomes. While several studies reported the superiority of the 8 th TNM edition in comparison to the previous 7 th TNM edition, in terms of both the discrimination ability among the various T subgroups and clinical outcomes, others argued against this interpretation. Synergistic cytotoxic chemotherapy with radiotherapy is most prevalent in treating LA NSCLC. Clinical trial experience from multiple references has reported that the risk of locoregional relapse and distant metastasis was less evident for patients treated with concomitant radiochemotherapy than radiotherapy alone. Nevertheless, concern persists as to whether major incidences of toxicity may occur due to the addition of chemotherapy. Cutting-edge technologies such as four-dimensional computed tomography (4D-CT) and volumetric modulated arc therapy (VMAT) should yield therapeutic gains due to their capability to conform radiation doses to tumours. On the basis of the preceding notion, the optimum radiotherapy technique for LA NSCLC has been a controversial and much-disputed subject within the field of radiation oncology. Notably, no single-perspective research has been undertaken to determine the optimum radiotherapy modality for LA NSCLC. The landscape of immunotherapy in lung cancer is rapidly expanding. Currently, the standard of care for patients with inoperable LA NSCLC is concurrent chemoradiotherapy followed by maintenance durvalumab according to clinical outcomes from the PACIFIC trial. An estimated 42.9% of patients randomly assigned to durvalumab remained alive at five years, and free of disease progression, thereby establishing a new benchmark for the standard of care in this setting.

Abstract: Background: Ovarian cancer is a huge therapeutic and financial problem for which approved treatments have already achieved their limit of efficiency. A cost-effective strategy to extend therapeutic options in this malignancy is drug repurposing aimed at overcoming chemoresistance. Here, angiotensin-converting enzyme inhibitors (ACE-I) are worth considering. Material and methods: We searched literature for publications supporting the idea of adjuvant application of ACE-Is in ovarian malignancy. Then, we searched The Cancer Genome Atlas databases for relevant alternations of gene expression patterns. We also performed in silico structure-activity relationship evaluation for predicting ACE-Is’ cytotoxicity against ovarian cancer cell lines. Finally, we reviewed the potential obstacles in ACE-Is repurposing process. Results: The alternation of angiotensin receptor expression in ovarian cancer translates into poorer patient survival. This confirms the participation of the renin-angiotensin system in ovarian carcinogenesis. In observational studies, ACE-Is were shown synergize with both, platinum-based chemotherapy as well as with antiangiogenic therapy. Consistently, our in silico simulation showed that ACE-Is are probably cytotoxic against ovarian cancer cells. However, the publications on their chemopreventive properties were inconclusive. In addition, some reports correlated ACE-Is use with increased general cancer incidence. We hypothesized that this effect could be associated with mutagenic nitrosamine formation in ACE-Is’ pharmaceutical formulations, as was the case with angiotensin receptor blockers (ARBs) and other well-established pharmaceuticals. Conclusions: Available data warrant further research into repositioning ACE-Is to ovarian cancer as chemosensitizers. Prior to this, however, a special research program is needed to detect possible genotoxic contaminants of ACE-Is.

Abstract: Background: Approximately 40% of patients with metastatic cancer will have spinal metastatic disease. Historically treated with external beam radiation therapy (EBRT) with limited durability in pain control, the increased lifespan of this patient population has necessitated more durable treatment results via spine radiosurgery/stereotactic body radiation therapy (SBRT). The goal of this study is to assess three-month pain freedom rates via the Spine Patient Optimal Radiosurgery Treatment for Symptomatic Metastatic Neoplasms (SPORTSMEN) randomized trial. Materials and methods: This study is a prospective randomized three-arm phase II trial which will recruit patients with symptomatic spine metastases. All patients will be randomized to standard-of care SBRT (24 Gy in 2 fractions), single-fraction SBRT (19 Gy in 1 fraction), or EBRT (8 Gy in 1 fraction), with the primary endpoint of three-month pain freedom (using the Brief Pain Inventory). We expect that SPORTSMEN will help definitively answer the efficacy of spine SBRT versus EBRT for achieving pain freedom, while defining the safety and efficacy of 19 Gy single-fraction spine SBRT. Local control will be defined according to Spine Response Assessment in Neuro-Oncology (SPINO) criteria. Discussion: This is the first phase II trial to objectively assess optimal spine SBRT dosing in the treatment of symptomatic spine metastatic disease, while assessing spine SBRT versus EBRT. Findings should allow for better determination of the efficacy of two-fraction spine SBRT versus EBRT in the United States, as well as for the novel single-fraction 19 Gy spine SBRT regimen in patients with symptomatic spine metastases. Trial Registration: Clinicaltrials.gov identifier: NCT05617716 (registration date: November 14, 2022).

Abstract: Background: The objective was to evaluate the efficacy and toxicity of curative radiotherapy in patients with sinonasal carcinoma and to identify prognostic factors influencing treatment outcomes. Materials and methods: The authors conducted a retrospective study of 61 consecutive patients treated with postoperative or definitive radiotherapy from 2002 to 2018 (median age 59 years, current/former smokers 71%, maxillary sinus 67%, nasal cavity 26%). The majority of patients were diagnosed with locally advanced disease (85% clinical stage ³ III). Regional cervical metastases were initially diagnosed in 23% of patients. The most common histology was squamous cell carcinoma (61%). Radiation therapy was preceded by radical surgery in 64% of patients. 29 patients received chemotherapy (48%). Results: The median follow-up was 53 months. The median total dose of radiotherapy achieved was 70 Gy. The 5- and 10-year locoregional control, distant control, overall survival, and disease-free survival were 74% and 64%, 90% and 90%, 51% and 35%, and 38% and 25%, respectively. Severe acute toxicity occurred in 36%, severe late toxicity in 23% of patients. Severe unilateral visual impairment occurred in 6 patients, temporal lobe necrosis in 1 patient, and osteoradionecrosis requiring surgery in 2 patients. Conclusion: The results of the study demonstrated the high effectiveness of curative treatment in patients with sinonasal carcinoma with long-term locoregional and distant control. The multivariate analysis indicated that N-staging, age, comorbidity score [as assessed by Adult Comorbidity Evaluation 27 (ACE-27)] and initial response to treatment were the strongest prognostic factors.

Abstract: Background: The safety and effectiveness of moderately hypofractionated post-operative radiation therapy for breast cancer were demonstrated by several trials. This study aimed to evaluate the current patterns of practice and prescription preference about moderately hypofractionated post-operative radiation therapy to assess possible aspects that affect the decision-making process regarding the use of fractionation in breast cancer patients in Latin America and the Caribbean (LAC). We also aimed to identify factors that can restrain the utilization of moderately hypofractionated post-operative radiation therapy for breast cancer. Materials an methods: Radiation oncologists from LAC were invited to contribute to this study. A 38-question survey was used to evaluate their opinions. Results: A total of 173 radiation oncologists from 13 countries answered the questionnaire. The majority of respondents (84.9%) preferred moderately hypofractionated post-operative radiation therapy as their first choice in cases of whole breast irradiation. Whole breast plus regional nodal irradiation, post-mastectomy (chest wall and regional nodal irradiation) without reconstruction, and post-mastectomy (chest wall and regional node irradiation) with reconstruction hypofractionated post-operative radiation therapy was preferred by 72.2% 71.1%, and 53.7% of respondents, respectively. Breast cancer stage, and flap-based breast reconstruction were the factors associated with absolute contraindications for the use of hypofractionated schedules. Conclusion: Even though moderately hypofractionated post-operative radiation therapy for breast cancer is considered a new standard to the vast majority of the patients, its unrestricted application in clinical practice across LAC still faces reluctance.

Abstract: Background: Postoperative radiation therapy (RT) is the standard treatment for almost all patients diagnosed with breast cancer. Even with modern RT techniques, parts of the heart may still receive higher doses than those recommended by clinically validated dose limit restrictions, especially when the left breast is irradiated. Deep inspiration breath hold (DIBH) may reduce irradiated cardiac volume compared to free breathing (FB) treatment. This study aimed to evaluate the dosimetric impact on the heart and left anterior descending coronary artery (LAD) in FB and DIBH RT planning in patients with left breast cancer. Materials and methods: A retrospective cohort study of women diagnosed with left-sided breast cancer submitted to breast surgery followed by postoperative RT from 2015 to 2019. All patients were planned with FB and DIBH and hypofractionated dose prescription (40.05 Gy in 15 fractions). Results: 68 patients were included in the study. For the coverage of the planned target volume evaluation [planning target volume (PTV) eval] there was no significant difference between the DIBH versus FB planning. For the heart and LAD parameters, all constraints evaluated favored DIBH planning, with statistical significance. Regarding the heart, median V16.8 Gy was 2.56% in FB vs. 0% in DIBH (p < 0.001); median V8.8 Gy was 3.47% in FB vs. 0% in DIBH (p < 0.001) and the median of mean heart dose was 1.97 Gy in FB vs. 0.92 Gy in DIBH (p < 0.001). For the LAD constraints D2% < 42 Gy, the median dose was 34.87 Gy in FB versus 5.8 Gy in DIBH (p < 0.001); V16.8 Gy < 10%, the median was 15.87% in FB versus 0% in DIBH (p < 0.001) and the median of mean LAD dose was 8.13Gy in FB versus 2.92Gy in DIBH (p < 0.001). Conclusions: The DIBH technique has consistently demonstrated a significant dose reduction in the heart and LAD in all evaluated constraints, while keeping the same dose coverage in the PTV eval.

Abstract: Background: In the treatment of vertebral bone metastases, estimating patient prognosis is important to select the optimal treatment strategy. The purpose of this study was to identify prognostic factors for vertebral bone metastases treated with palliative radiotherapy and to establish a nomogram for predicting patient survival. Materials and methods: We analyzed patients who underwent palliative radiotherapy for vertebral bone metastasis between January 2010 and December 2020 at a single institution. Exclusion criteria were as follows: (1) primary bone malignancy, (2) stereotactic body radiotherapy, (3) concurrent radiotherapy to sites other than the vertebral bone, (4) radiotherapy to other sites within 12 weeks before or after the current radiotherapy, and (5) lack of more than half of blood test data before radiotherapy. Results: A total of 487 patients met the inclusion criteria. Clinical and hematologic data were collected from the patient record system. Patients were divided into training and test groups in a 7:3 ratio. Multivariate Cox regression analysis in the training cohort revealed six significant factors, including a history of chemotherapy, primary

Abstract: Background : Radiotherapy has a significant side effect known as radiation-induced secondary cancer. This study aims to evaluate the dose and secondary cancer risk for women with rectal cancer treated with three-dimensional conformal radiation therapy (3DCRT) to the organs at risk (OARs) and some sensitive organs using different types of radiation-induced cancer risk prediction models, including Biological Effects of Ionizing Radiation (BEIRVII), Environmental Protection Agency (EPA) and International Commission on Radiological Protection (ICRP)

Abstract: Beam matching is widely used to ensure that linear accelerators used in radiotherapy have equal dosimetry characteristics. Small-field output factors (OF) were measured using different detectors infour beam-matched linear accelerators and the measured OFs were compared with existing treatment planning system (TPS) Monte Carlo algorithm calculated OFs.Three Elekta Versa HDTM and one Elekta InfinityTMlinear accelerators with photon energies of 6 MV flattening filter (FF), 10 MVFF, 6 MV flattening filter free (FFF) and 10 MVFFF were used in this study. All the Linac'swere beam-matched, Dosimetry beam data were ± 1% compare with Reference Linac. Ten different type of detectors (four ionizationchambers and six diode detectors) were used for small-field OF measurements. The OFs were measured for field sizes of 1 × 1 to 10 × 10 cm2, and normalized to 10 × 10 cm2 field size. The uncorrected and corrected OFs were calculated from these measurements. The corrected OF was compare with existing treatment planning system (TPS) Monte Carlo algorithm calculated OFs.The small-field corrected and Uncorrected OF variations among the linear accelerators was within 1% for all energies and detectors. An increase in field size led to a reduction in the difference between OFs among the detectors, which was the case for all energies. The RSD values decreased with increasing field size. The TRS 483 provided Detector-specificoutput-correction factor (OCF) reduced uncertainty in small-field measurements.It is necessary to implement the OF-correction of small fields in a TPS. Special care must be taken to incorporate the corrected small-field OF in a TPS.

Abstract: Epidemiologic studies have demonstrated race as a predictor of worse oncological outcomes. To better understand the effect of race on oncological outcomes, we utilized the Surveillance, Epidemiology, and End Results (SEER) database to determine what treatment courses are provided to minority patients and how this impacts survival.A retrospective review of bone and soft tissue sarcoma cases was performed using the SEER database for a minimum 5-year survival rate (SR) using Kaplan-Meier curves. Categorical variables were compared using Pearson's χ2 test and Cramer V. Kaplan-Meier curves were used to determine survival rates (SR) and Cox regression analysis was used to determine hazard ratios (HRs).Races that had an increased risk of death included Native American/Alaska Native (NA/AN) [hazard ratio (HR): 1.36, 95% confidence interval (CI): 1.049-1.761, p = 0.020) and Black (HR = 1.17, 95% CI: 1.091-1.256, p < 0.001). NA/AN individuals had the lowest SR (5-year SR = 70.9%, 95% CI: 63.8-78.0%, p < 0.001). The rate of metastasis at diagnosis for each race was 13.07% - Hispanic, 10.62% - NA/AN, 12.77% - Black, 10.61% - Asian/Pacific Islander (A/PI), and 9.02% - White individuals (p < 0.001). There were increases in the rate of metastasis at diagnosis and decreases in rates of surgical excision for Hispanic and Black patients (p < 0.001).Race is determined to be an independent risk factor for death in NA/AN and Black patients with sarcomas of the extremities. Access to healthcare and delay in seeking treatment may contribute to higher rates of metastasis upon diagnosis for minority patients, and decreased rates of surgical excision could be associated with poor follow up and lack of resources.

Abstract: Clinical audits are an important tool to objectively assess clinical protocols, procedures, and processes and to detect deviations from good clinical practice. The main aim of this project is to determine adherence to a core set of consensus- based quality indicators and then to compare the institutions in order to identify best practices.We conduct a multicentre, international clinical audit of six comprehensive cancer centres in Poland, Spain, Italy, Portugal, France, and Romania as a part of the project, known as IROCATES (Improving Quality in Radiation Oncology through Clinical Audits - Training and Education for Standardization).Radiotherapy practice varies from country to country, in part due to historical, economic, linguistic, and cultural differences. The institutions developed their own processes to suit their existing clinical practice.We believe that this study will contribute to establishing the value of routinely performing multi-institutional clinical audits and will lead to improvement of radiotherapy practice at the participating centres.

Abstract: Background: The aim was perusal of the treatment strategies, clinical outcomes and factors impacting these outcomes in thymoma. Materials and methods: A total of 119 patients diagnosed and treated cases of thymoma, at our hospital, were taken for analysis. Thirty-one patients were excluded due to inadequate medical records. Descriptive statistics were used to report demographic and clinical characteristics. Time period between diagnosis and death was defined as overall survival (OS). Multivariate analysis (MVA), using cox regression modelling, was done by including clinicopathological factors in a bid to identify prognostic factors influencing OS. SPSS version 26 was used for statistical analysis. Results: The mean age of the patients was 52.17 years and 39 (44.3%), 19 (21.6%), 17 (1.3%) and 13 (4.8%) patients presented with Masaoka stage II, IV, III and I, respectively. Surgery was done in 64 (72.7%) of the patients as a part of the treatment strategy. Radiotherapy was administered to a total of 57 patients with a median dose of 50.4 Gy. Early Masaoka stage at presentation and use of surgery in the treatment plan were statistically significant prognostic factors for a better overall survival on multivariate analysis. Conclusion: Judicious use of radiotherapy and chemotherapy in locally advanced cases may render them resectable. In a bid to gain good survival rates, aggressive multimodality treatment should be offered to the patients.

Abstract: Background: The aim of the study was to perform dosimetric comparisons of helical (H) and TomoDirect (TD) plans for whole-breast irradiation (WBI) with simultaneous integrated boost (SIB) in early-stage breast cancer patients undergoing breast conserving surgery. Materials and methods: Fifty patients, 25 with left-side and 25 with right-side tumors, were determined for a treatment planning system for a total dose of 50.4Gy in 1.8Gy per fraction to WBI, with a SIB of 2.3Gy per fraction delivered to the tumor bed. The planning target volume (PTV) doses and the conformity (CI) and homogeneity indices (HI) for PTV breast and PTV boost , as well as organ-at-risk (OAR) doses and treatment times, were compared between the H and TD plans. Results: All plans met the PTV coverage criteria for the H plan, except for mean V107 of PTV breast for TD plan. The H plan yielded better homogeneity and conformity of dose distribution compared to the TD plan. The ipsilateral mean lung doses were not significantly different between the two plans. The TD plans is advantageous for mean doses to the heart, contralateral breast and lung, spinal cord, and esophagus than the H plans. In both the H and TD plans, the right-sided breast patients had lower heart dose parameters than the left-sided breast patients. The TD plan is superior to the H plan in sparing the contralateral breast and lung by decreasing low-dose volumes. Conclusions: While the OAR dose advantages of TD are appealing, shorter treatment times or improved dose homogeneity and conformity for target volume may be advantageous for H plan.

Abstract: Background: Whole-brain radiotherapy is associated with neurocognitive decline and decreased quality-of-life (QOL) among survivors of brain metastasis. Hippocampal-avoidance whole-brain radiotherapy (HA-WBRT) has shown advantage in delaying or preventing the neurocognitive decline while maintaining disease control. This study was done to assess the benefits and feasibility of HA-WBRT in patients with cerebral metastasis in terms of preservation of neurocognitive function and quality of life. Materials and methods: 27 patients with brain metastasis treated by HA-WBRT and having the records of detailed neurocognitive-assessments were analysed from the database of our hospital. The patients were treated with HA-WBRT to a total dose of 30 Gy in 10 fractions with LINAC based IMRT using the VMAT technique. Cognitive function assessment was carried out using “Examination of the Cognitive Functions” scale provided by Bangur-Institute-of-Neurosciences, Kolkata, 2 weeks prior to radiotherapy and post-treatment two-monthly up to 6 months followed by every 3 months till the last follow up. QOL was assessed at the same interval using the Functional Assessment of Cancer Therapy with Brain Subscale (FACT-BR). Follow-up was done till the date of death. Results: Mean relative cognitive decline percentage decreased over subsequent follow-up visits and was 13% (SD ± 6%), 5% (SD ± 5%), 5% (SD ± 9%) and 2% (SD ± 12%) at 2 months, 6 months, 9 months and 12 months, respectively (p ≤ 0.05). Statistically significant improvement was seen in the mean social-wellbeing (SWB) parameter of QOL (8%. ± 13%, 12%. ± 16%, 7%. ± 20%, no change at 2 months, 4 months, 6 months and 9 months, respectively) (p ≤ 0.05). Mean relative decline in the Emotional-Well Being (EWB) parameter was significant only at 12 months and was 20% (SD ± 35%) (p = 0.04). Mean FACT-BR total Score showed a slight decrease till 9 months from baseline, and then showed a slight improvement up to 12 months. Conclusion: HA-WBRT is feasible with LINAC-based IMRT using the VMAT technique and beneficial to the patients in preserving neurocognitive function and quality of life without compromising disease control.

Abstract: Background: This study aimed to evaluate the dosimetric influence of 6-dimensional (6D) interfractional setup error in tongue cancer treated with intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) using daily kilovoltage cone-beam computed tomography (kV-CBCT). Materials and methods: This retrospective study included 20 tongue cancer patients treated with IMRT (10), VMAT (10), and daily kV-CBCT image guidance. Interfraction 6D setup errors along the lateral, longitudinal, vertical, pitch, roll, and yaw axes were evaluated for 600 CBCTs. Structures in the planning CT were deformed to the CBCT using deformable registration. For each fraction, a reference CBCT structure set with no rotation error was created. The treatment plan was recalculated on the CBCTs with the rotation error (R Error ), translation error (T Error ), and translation plus rotation error (T+R Error ). For targets and organs at risk (OARs), the dosimetric impacts of R Error , T Error , and T+R Error were evaluated without and with moderate correction of setup errors. Results: The maximum dose variation ΔD (%) for D 98% in clinical target volumes (CTV): CTV-60, CTV-54, planning target volumes (PTV): PTV-60, and PTV-54 was –1.2%, –1.9%, –12.0%, and –12.3%, respectively, in the T+R Error without setup error correction. The maximum ΔD (%) for D 98% in CTV-60, CTV-54, PTV-60, and PTV-54 was –1.0%, –1.7%, –9.2%, and –9.5%, respectively, in the T+R Error with moderate setup error correction. The dosimetric impact of interfractional 6D setup errors was statistically significant (p < 0.05) for D 98% in CTV-60, CTV-54, PTV-60, and PTV-54. Conclusions: The uncorrected interfractional 6D setup errors could significantly impact the delivered dose to targets and OARs in tongue cancer. That emphasized the importance of daily 6D setup error correction in IMRT and VMAT.