Exploring the Evolving Landscape of Stereotactic Body Radiation Therapy in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) carries significant morbidity and mortality. Management of the HCC requires a multidisciplinary approach. Surgical resection and liver transplantation are the gold standard options for the appropriate settings. Stereotactic body radiation therapy (SBRT) has emerged as a promising treatment modality in managing HCC; its use is more studied and well-established in advanced HCC (aHCC). Current clinical guidelines universally endorse SBRT as a viable alternative to radiofrequency ablation (RFA), transarterial chemoembolisation (TACE), and transarterial radioembolisation (TARE), a recommendation substantiated by literature demonstrating comparable efficacy among these modalities. In early-stage HCC, SBRT primarily manages unresectable tumours unsuitable for ablative procedures such as microwave ablation and RFA. SBRT has been incorporated as a modality to downstage tumours or as a bridge to transplant. In the case of intermediate or advanced HCC, SBRT offers excellent results either as a single modality or adjunct to other locoregional modalities such as TACE/TARE. Recent data from late-stage HCC patients illustrate the effectiveness of SBRT in achieving local tumour control while minimising damage to surrounding healthy liver tissue. It has promising local control of approximately 80-90% in managing HCC. Additional prospective data comparing the efficacy of SBRT with the first-line recommended therapies such as RFA, TACE, and surgery are essential. The standard of care for patients with advanced/metastatic disease is systemic therapy (immunotherapy/tyrosine kinase inhibitors). SBRT, in combination with immune-checkpoint inhibitors, has an immune-modulatory effect that results in a synergistic effect. Recent findings indicate that the combination of immunotherapy and SBRT in HCC is well-tolerated and exhibits synergistic effects. Further exploration of diverse immunotherapy and radiotherapy strategies is essential to identify the appropriate time for combination treatments and to optimise dose and fraction regimens. Prospective, randomised studies are imperative to establish SBRT as the primary treatment for HCC.

What is the Long-term Wear of a 5-Mrad Highly Crosslinked Polyethylene Liner? A 14-year RSA Study.

BACKGROUND: Lower doses of irradiation (≤ 5 Mrad) during the manufacture of highly crosslinked polyethylene acetabular liners may result in less crosslinking and an increased wear rate. Radiostereometric analysis (RSA) studies have found that wear of more highly irradiated highly crosslinked polyethylene liners (7 to 10 Mrad) decreases at longer-term follow-up compared with earlier reports of the same cohorts. Although wear of 5-Mrad irradiated liners appears to increase at midterm follow-up, it is unclear whether that remains true at longer follow-up. QUESTIONS/PURPOSES: We asked: (1) In patients who underwent THA with a 5-Mrad highly crosslinked polyethylene liner, what is the wear rate evaluated with RSA during the first 14 years? (2) Does the wear rate decrease after 6 years in situ? METHODS: This is a brief follow-up of prior RSA studies performed at 2 and 6 years. We prospectively reviewed the longer-term wear rate in 13 patients who underwent primary THAs with the same design of a 5-MRad irradiated crosslinked acetabular liner and a 28-mm cobalt-chromium articulation. Of the initial 30 patients who were enrolled, 13 (43%) were available at the 14-year timepoint; nine patients had died, 1 patient had withdrawn, 1 had an intraoperative fracture, 3 patients were too infirm to have radiographs, 2 had no baseline RSA radiographs, and 1 had poor-quality RSA images. Tantalum markers were inserted during surgery, and all patients had RSA radiographic examinations at 1 week, 6 months, and 1, 2, 6, and 14 years postoperatively. RESULTS: The mean ± standard deviation proximal, 2D, and 3D wear rates calculated between 1 year and 14 years were 0.019 ± 0.013 mm, 0.022 ± 0.015 mm, and 0.025 ± 0.019 mm per year, respectively. No patient had proximal 2D or 3D wear rates exceeding 0.06 mm per year. An increasing wear rate over time was measured for proximal and 2D wear rates between 6 and 14 years (0.024 and 0.030 mm per year) compared with that between 1 and 6 years (0.008 and 0.010 mm per year; p = 0.03). CONCLUSION: The proximal, 2D, and 3D wear of a highly crosslinked polyethylene liner produced using 5-Mrad radiation remains low in the longer-term. With the small numbers available in a long-term RSA study such as this, we confirmed that the wear rate did not decrease at longer-term follow-up, unlike previous RSA studies of more highly irradiated highly crosslinked polyethylene liners. Nevertheless, the wear rate remains very low and below the threshold typically associated with the development of osteolysis (0.1 mm/year of wear). This should provide assurance to orthopaedic surgeons monitoring patients with this 5-Mrad irradiated liner in situ, while providing useful information to manufacturers of future highly crosslinked polyethylene liners. LEVEL OF EVIDENCE: Level IV therapeutic study.

Assessment of symptomatic response to intravesical alkalinized lidocaine, bupivacaine, heparin and steroids in patients with bladder pain syndrome.

Bladder Pain Syndrome (BPS) is a puzzling and complicated disorder. 12 such patients, with a mean age 48.3 years, were treated with weekly intravesical instillation of admixture of alkalinized lidocaine, bupivacaine, heparin and steroids for six weeks. Evaluating the benefits of this therapy, patients experienced 82.2% & 90.9% relief at 3rd & 6th week of instillation. After completion of six cycles of therapy, patients experienced 68.7% & 65.3% relief at 3rd & 6th month follow up, concluding the early and long term relief of BPS.

Double blind randomized controlled trial of efficacy of ormeloxifene for the treatment of fibroadenoma (The FIBROCENT study).

BACKGROUND: We evaluated the effectiveness of Ormeloxifene (Centchroman) on regression of Fibroadenoma in a double-blind randomized controlled trial. METHODS: Patients with biopsy proven Fibroadenoma were enrolled between March 2023 and October 2023 and divided in two arms- Ormeloxifene group and Placebo group. Effectiveness of the treatment was evaluated using USG. No residual mass was defined as complete regression and more than 30% decrease in size was considered as partial regression. RESULTS: A total of 130 consecutive patients with Fibroadenoma were randomized to Ormeloxifene group (n = 65) and Placebo Group (n = 65). Complete regression was observed in 9% (6/65) patients in Ormeloxifene group and 10.8% (7/65) in Placebo Group at the end of 12 weeks (p = 0.49). Twenty one patients taking Ormeloxifene reported adverse events as compared to none in the other group. CONCLUSION: In our study Ormeloxifene was not found to be effective in treatment of fibroadenoma and had concerning side effects.

Patient Perspectives After Surgery-Related Complications Among Breast Cancer Patients from a LMIC.

Long-term quality of life in breast cancer patients has been studied and published regularly. However, the lived experiences of patients who develop complications after surgery are not well understood. Determining this experience of patients is challenging in most low- and middle-income countries where the majority of patients belong to poor strata of society and are uneducated. We aimed to explore the thoughts, feelings, and experiences of patients with surgery-related complications after breast cancer surgery. Purposive sampling was used to identify patients who developed any postoperative complication, and semi-structured interviews were conducted. Common patterns of patient experiences were identified and analyzed using descriptive thematic analysis. Twenty-eight patients out of 210 developing complications postoperatively were identified. The median age was 48 years (range 32-65 years). The majority (n = 26) were housewives, educated below the primary level (n = 11) and below the poverty line (n = 13). Complications included seroma (n = 17), flap necrosis and infection (n = 5), and hematoma (n = 1). Seven domains emerged from the interviews-knowledge of complications, psychological impact, burden, disruptiveness, social impact, relationship with the surgical team, and suggestions to improve the experience. The themes identified in the present study provide insights into the lived experiences and can inform the future development of patient-reported outcome measures and quality improvement programs, including more effective pre-operative counseling and consent. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-023-01721-z.

Prospective randomised phase II trial evaluating adjuvant pelvic radiotherapy using either IMRT or 3-Dimensional planning for endometrial cancer.

OBJECTIVE: To compare the incidence of grade ≥2 gastrointestinal (GI) or genitourinary (GU) toxicity for patients undergoing 3DRT versus IMRT in the postoperative setting for endometrial cancer. METHODS: Eligible patients were post-operatively randomly assigned to one of two parallel groups in a 1:1 ratio, to have their RT delivered using either a 3DRT technique or using IMRT. The prescription dose was 45 Gy in 25 fractions over 5 weeks followed by vaginal vault brachytherapy. Toxicity was graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 3.0. Fisher's exact tests were used to test for associations between toxicity and arm. Differences in dosimetric parameters for patients with or without toxicity were tested using Mann-Whitney U-tests. RESULTS: 84 patients with a median age of 62 were evaluable for primary outcome. The median follow-up was 52 months. 14 (35%) participants from the 3DRT arm and 15 (34%) from the IMRT arm experienced acute grade ≥2 GI toxicity with older patients having a statistically higher risk of grade ≥2 acute GI toxicity. 20 (50%) participants from the 3DRT arm and 25 (57%) from the IMRT arm experienced acute grade ≥2 GI or GU toxicity (p = .662). 12 (30%) patients from the 3DRT arm and 17 (39%) from the IMRT arm experienced acute grade ≥2 GU toxicity (p = .493). CONCLUSION: Although IMRT can reduce dose to normal tissue, in this study no benefit in acute GI or GU toxicity outcome was seen.

Vascular cell-adhesion molecule 1 (VCAM-1) regulates JunB-mediated IL-8/CXCL1 expression and pathological neovascularization.

Vascular adhesion molecules play an important role in various immunological disorders, particularly in cancers. However, little is known regarding the role of these adhesion molecules in proliferative retinopathies. We observed that IL-33 regulates VCAM-1 expression in human retinal endothelial cells and that genetic deletion of IL-33 reduces hypoxia-induced VCAM-1 expression and retinal neovascularization in C57BL/6 mice. We found that VCAM-1 via JunB regulates IL-8 promoter activity and expression in human retinal endothelial cells. In addition, our study outlines the regulatory role of VCAM-1-JunB-IL-8 signaling on retinal endothelial cell sprouting and angiogenesis. Our RNA sequencing results show an induced expression of CXCL1 (a murine functional homolog of IL-8) in the hypoxic retina, and intravitreal injection of VCAM-1 siRNA not only decreases hypoxia-induced VCAM-1-JunB-CXCL1 signaling but also reduces OIR-induced sprouting and retinal neovascularization. These findings suggest that VCAM-1-JunB-IL-8 signaling plays a crucial role in retinal neovascularization, and its antagonism might provide an advanced treatment option for proliferative retinopathies.

Unravelling the role of immunohistochemistry in giant cell lesions of jaws: A systematic review.

Controversies exist in literature regarding nature, pathogenesis, and behaviour of giant cell lesions (GCLs) of jaws. Studies were attempted to solve these mysteries with immunohistochemical analysis, using various biological markers. Thus, the aim of this review is to appraise the role of immunohistochemistry (IHC) in evaluating the pathogenesis, cellular phenotype, nature, and behaviour of GCLs of jaws. PubMed, PubMed Central, and Clinical Key (Medline) databases were searched electronically irrespective of date of publication with assortment of several independent terms. Fifty-five articles that fulfilled the eligibility criteria were included in the review. Out of 55 included articles, 49 were associated with nature, pathogenesis, and behaviour and six articles were associated with treatment and outcome prediction. Although IHC solved some of the controversies associated with GCLs of jaws such as the osteoclastic phenotype of multinucleated giant cells, immunoexpression of proliferative markers does not distinct non-aggressive from aggressive central GCL but the nature, histogenesis, pathogenesis, and exact behaviour still remain debatable. With regard to formulation of treatment plan, immunohistochemical analysis revealed that expression of glucocorticoid and calcitonin receptors could act as a tool to decide the therapeutic strategy and aid in therapeutic adjustments according to evolution of the lesion.

Role of stereotactic body radiotherapy for inferior vena cava tumour thrombus in hepatocellular carcinoma.

INTRODUCTION: To evaluate the role of stereotactic body radiotherapy (SBRT) in hepatocellular carcinoma (HCC) patients with inferior vena cava tumour thrombus (IVCTT) who are not suitable for other loco-regional therapies. METHODS: This is an observational retrospective study done between May 2020 and April 2022. The data of 17 patients who underwent SBRT were collected. Patients of Child-Pugh score (CPS) A5-B7 and along with a liver reserve of ≥700 cc were included. Local control (LC), overall survival (OS) and adverse events including hepatic decompensation were carefully recorded. RESULTS: In the cohort, the tumour thrombus was extended to the right atrium in nine (52.9%) patients, and regional nodal and lung were found in 60% and 31.4% of patients respectively. The median gross tumour volume (GTV) was 745 cc (107-1,650 cc). The median SBRT dose prescription was 35 Gy (25-45 Gy) in 5-10 fractions. At 6 months, LC and OS were 80% and 75% respectively. On multivariate analysis, an ALBI score >-2.36 was found to be the predictor for the poor OS. Post-SBRT, a change in CPs by 2 points was observed in one patient (5.9%) which was managed conservatively. Post-radiation, improvement in pain and discomfort was observed in 92.3% and 87% of patients, respectively and bone metastasis related pain was also resolved. CONCLUSION: Stereotactic body radiotherapy is a safe and feasible option for HCC patients with IVC and right atrium tumour thrombosis. It not only improves the quality of life but also results in good LC and OS with acceptable toxicity. SBRT should be considered in a multidisciplinary fashion for patients presenting with tumour thrombosis extending to IVC and the right atrium.

Role of palliative SBRT in barcelona clinic liver cancer-stage C hepatocellular carcinoma patients.

OBJECTIVE: To evaluate the role of palliative stereotactic body radiation therapy (SBRT) in Barcelona Clinic Liver Cancer stage­C (BCLC-C) hepatocellular carcinoma (HCC) patients who are not suitable for other loco-regional therapies. MATERIALS AND METHODS: It is an observational retrospective study done between May 2020 and September 2021. The data were collected from 35 patients of advanced HCC who underwent SBRT. Patients of Child Pugh status (CPs) A5-B7 and with a liver reserve of ≥ 700cc were included. Local control (LC), overall survival (OS) and adverse events including decompensation were carefully recorded. RESULTS: In the cohort, Portal vein and IVC tumor thrombosis were present in 33 (94.3%) and 8 (22.85%) patients, respectively. Lung and nodal metastasis were found in 11 (31.4%) and 21 (60%) of patients, respectively. The median gross tumor volume (GTV) was 563cc (range 80-1925cc). The median SBRT dose prescription was 35 Gy (range 25-40 Gy) in 5-10 fractions. Post radiation therapy, there was improvement in pain and discomfort in 24 out of 29 (82.75%) and 18 out of 23 (78%) patients respectively. Also bone metastasis related pain was improved in all 3 (100%) patients. One year LC, and OS were 80% and 30% respectively. On multivariate analysis, the GTV volume > 750cc and PIVKA-II > 8000 mAU/ml remained the predictor factor for poor OS. Post SBRT, change in child-pugh score by 1 point was observed in 7 patients (20%) which was managed conservatively. CONCLUSION: SBRT is a safe and feasible option for BCLC­C HCC. It not only improves the quality of life by symptom control but also results in good LC and OS with acceptable toxicity. SBRT should be considered in a multidisciplinary fashion for patients presenting with advanced HCCs.

The Biochemistry and Physiology of A Disintegrin and Metalloproteinases (ADAMs and ADAM-TSs) in Human Pathologies.

Metalloproteinases are a group of proteinases that plays a substantial role in extracellular matrix remodeling and its molecular signaling. Among these metalloproteinases, ADAMs (a disintegrin and metalloproteinases) and ADAM-TSs (ADAMs with thrombospondin domains) have emerged as highly efficient contributors mediating proteolytic processing of various signaling molecules. ADAMs are transmembrane metalloenzymes that facilitate the extracellular domain shedding of membrane-anchored proteins, cytokines, growth factors, ligands, and their receptors and therefore modulate their biological functions. ADAM-TSs are secretory, and soluble extracellular proteinases that mediate the cleavage of non-fibrillar extracellular matrix proteins. ADAMs and ADAM-TSs possess pro-domain, metalloproteinase, disintegrin, and cysteine-rich domains in common, but ADAM-TSs have characteristic thrombospondin motifs instead of the transmembrane domain. Most ADAMs and ADAM-TSs are activated by cleavage of pro-domain via pro-protein convertases at their N-terminus, hence directing them to various signaling pathways. In this article, we are discussing not only the structure and regulation of ADAMs and ADAM-TSs, but also the importance of these metalloproteinases in various human pathophysiological conditions like cardiovascular diseases, colorectal cancer, autoinflammatory diseases (sepsis/rheumatoid arthritis), Alzheimer's disease, proliferative retinopathies, and infectious diseases. Therefore, based on the emerging role of ADAMs and ADAM-TSs in various human pathologies, as summarized in this review, these metalloproteases can be considered as critical therapeutic targets and diagnostic biomarkers.

Low-cost solutions incorporated in a standard surgical pathway for early breast cancer: A pilot study.

We present the results of incorporation of low-cost solutions to provide a standard surgical care for early breast cancer (EBC) patients. This surgical pathway consists of a low-cost vacuum-assisted core needle biopsy, sentinel lymph node biopsy (SLNB) using low-cost methylene blue and fluorescin dyes under local anesthesia and oncoplastic breast surgery. Patients assessed as clinically node-negative axilla underwent such treatment. SLNB using low-cost dyes was performed without any complication. Oncoplastic surgical techniques were opted for in 32 patients, and the lumps were all excised with a ∼1-cm all-around margin on the final histopathological examination. Standard breast cancer surgery can be provided in low-resource settings to eligible EBC patients with low-cost solutions.

Potential implications of mobile applications in oral cancer.

ABSTRACT: The modern era has observed vast technological advancements with a definite impact on the health sector. There has been an upsurge in mobile applications (mApps) used for varied purposes. Many mApps are available that target different arenas in dentistry including a range of oral health issues, the most important being oral cancer. These mApps with specific algorithms have been used for risk assessment, screening and diagnosis of oral potentially malignant and malignant disorders. Other benefits include remote consultation, timely referral, treatment of the disease, self monitoring and adherence to medications. Therefore, this review is designed to appraise the utility of mobile apps in oral cancer. The systematic research of the literature was done to find relevant articles regarding the development and applications of mApps in oral cancer by using specific research engines. PubMed, Cochrane and Clinical Key databases were searched electronically, irrespective of date of publication, with an assortment of several independent terms. A total of 423 articles were accessed, and screened. After applying the definite inclusion and exclusion criteria, 9 articles were finally selected which highlighted the impact of mApps in oral cancer. It was concluded that the potential of mobile applications could be harnessed judiciously to improve the screening, diagnosis and treatment of oral cancer.

Bioengineered 3D microfibrous-matrix modulates osteopontin release from MSCs and facilitates the expansion of hematopoietic stem cells.

The osteopontin (OPN) released from mesenchymal stem cells (MSCs) undergoing lineage differentiation can negatively influence the expansion of hematopoietic stem cells (HSCs) in coculture systems developed for expanding HSCs. Therefore, minimizing the amount of OPN in the coculture system is important for the successful ex vivo expansion of HSCs. Toward this goal, a bioengineered three dimensional (3D) microfibrous-matrix that can maintain MSCs in less OPN-releasing conditions has been developed, and its influence on the expansion of HSCs has been studied. The newly developed 3D matrix significantly decreased the release of OPN, depending on the MSC culture conditions used during the priming period before HSC seeding. The culture system with the lowest amount of OPN facilitated a more than 24-fold increase in HSC number in 1 week time period. Interestingly, the viability of expanded cells and the CD34+   pure population of HSCs were found to be the highest in the low OPN-containing system. Therefore, bioengineered microfibrous 3D matrices seeded with MSCs, primed under suitable culture conditions, can be an improved ex vivo expansion system for HSC culture.

Barriers and challenges in providing standard breast cancer care in low resource settings.

In this study, we investigated the barriers to the delivery of internationally accepted breast cancer care in low resource settings (LRS) as compared to well-endowed resource settings (WRS) via an online survey. The survey was completed by 199 surgeons from eleven countries: 51 from WRS and 148 from LRS, based on our definition. The two most common facilities lacking in LRS were sentinel lymph node biopsy and immune-histochemistry (67% and 60% respectively). Only 22% respondents from LRS confirmed that all their eligible patients received hormonal therapy and only 8% radiotherapy as compared to 98% and 75% from WRS. Widespread limitations exist in most LRS, making internationally accepted breast cancer treatment guidelines impossible to follow, and thus resulting in suboptimal cancer care.

IL-33 enhances Jagged1 mediated NOTCH1 intracellular domain (NICD) deubiquitination and pathological angiogenesis in proliferative retinopathy.

Pathological retinal neovascularization (NV) is a clinical manifestation of various proliferative retinopathies, and treatment of NV using anti-VEGF therapies is not selective, as it also impairs normal retinal vascular growth and function. Here, we show that genetic deletion or siRNA-mediated downregulation of IL-33 reduces pathological NV in a murine model of oxygen-induced retinopathy (OIR) with no effect on the normal retinal repair. Furthermore, our fluorescent activated cell sorting (FACS) data reveals that the increase in IL-33 expression is in endothelial cells (ECs) of the hypoxic retina and conditional genetic deletion of IL-33 in retinal ECs reduces pathological NV. In vitro studies using human retinal microvascular endothelial cells (HRMVECs) show that IL-33 induces sprouting angiogenesis and requires NFkappaB-mediated Jagged1 expression and Notch1 activation. Our data also suggest that IL-33 enhances de-ubiquitination and stabilization of Notch1 intracellular domain via its interaction with BRCA1-associated protein 1 (BAP1) and Numb in HRMVECs and a murine model of OIR.

Assessment of the systemic toxicity of Laghu vishagarbha taila, an Ayurvedic medicated oil formulation after dermal exposure.

Laghu vishagarbha taila (LVT) is a medicated oil preparation used in the Ayurvedic system of medicine and applied topically for the treatment of painful musculoskeletal and inflammatory disorders. It contains some mildly poisonous phytoconstituents which may show untoward effects upon application. The present study evaluated the toxicity of LVT in the acute, subacute, and subchronic dermal toxicity study in Wistar rats. LVT was tested for its compliance using physicochemical and analytical parameters as per standard methods prescribed in Ayurvedic Pharmacopoeia of India, while acute, subacute, and subchronic toxicity studies were carried out as per OECD 402, 410, and 411 guidelines, respectively. In the acute dermal toxicity study, a single dose of LVT (2000 mg/kg) was applied topically to rats, while in subacute and subchronic dermal toxicity study, the rats were topically applied LVT (1000 mg/kg) up to 28 and 90 days, respectively. LVT did not cause any alterations in clinical signs and no mortality or moribund stage was observed. The change in weekly body weight was insignificant compared with the vehicle control group. In subacute and subchronic dermal toxicity study, there were no significant changes in behavior, body weight, feed consumption, biochemical and hematological parameters, organ weight, and histological parameters compared with vehicle control rats. Topical application of single and repeated doses of LVT in rats did not exhibit adverse effects and suggests that the LD50 of LVT is more than 2000 mg/kg in the acute dose and NOAEL is more than 1000 mg/kg/day in repeated dose application.

Validation sentinel lymph node biopsy study in cN0 axilla using low-cost dual dye technique: potential solution for resource poor settings.

BACKGROUND: Sentinel lymph node biopsy (SLNB) using radio-pharmaceutical and a blue dye is gold standard for axillary staging in clinically node-negative breast cancer. High costs and limited availability of radio-pharmaceutical and/or gamma probe are major deterrents in performing SLNB in developing countries. In this study, we evaluated feasibility of SLN identification (SLN-IR) of fluorescein-guided (FG) SLNB in combination with methylene blue dye (MBD). METHODS: This was a prospective cross-sectional non-randomized validation study in patients with clinically node-negative axilla. Patients underwent validation SLNB using fluorescein (and blue LED light) and MBD. Axillary dissection was performed irrespective of SLNB histology. SLIN-IR and False Negative Rate (FNR) were assessed for both groups. RESULTS: The SLNs were identified in 29 (96.6%) pre-chemotherapy patients and 23 (82%) post Neoadjuvant Chemotherapy (NACT) patients. The median number of sentinel lymph nodes identified was 3 (range of 1-5) in pre-chemotherapy patients and 1 (range of 1-3) in post NACT patients. The SLN-IR using MBD was 90%, FD was 86.7% and combined MBD FD was 96.7% in pre-chemotherapy patients. The SLN-IR using MBD was 82%, FD was 71% and combined MBD FD was 82% in in post NACT patients. The false negative rate (FNR) in pre-chemotherapy group was 8.0% (MBD), 8.3% (FD) and 7.4% (MBD + FD). The FNR in post NACT group was 8.7% (MBD), 10% (FD) and 8.7% (MBD + FD). CONCLUSION: This prospective validation study showed adequate SLN-IR and FNR using low-cost dual dyes in early breast cancer patients and can be used in low resource settings. However, SLNB in post NACT axilla though viable along with a satisfactory FNR, is associated with low identification rate and needs further evaluation.

Degree of reduction in normal liver complication probability from free-breathing to breath-hold liver SBRT: a dose-escalation strategy using radiation dose-volume effect.

Introduction. This study aimed to analyze the degree of reduction in normal liver complication probability (NTCP) from free-breathing (FB) to breath-hold (BH) liver SBRT. The effect of the radiation dose-volume on the mean liver dose (MLD) was also analyzed due to dose prescription, normal liver volume (NLV), and PTV.Materials and Methods. Thirty-three stereotactic body radiation therapy (SBRT) cases of hepatocellular carcinoma were selected, retrospectively. For FB, the treatments were planned on average intensity projection scan (CTavg), and patient-specific internal target volume (ITV) margins were applied. To simulate the BH treatment, computed tomography (CT) scan correspond to the 40%-50% of the respiratory cycle (CT40%-50%) was chosen, and an appropriate intrafraction margin of 2 mm, 1.5 mm, and 1.5 mm were given in craniocaudal (CC), superior-inferior (SI), and lateral direction to generate the final iGTV. As per RTOG 1112, all organs at risk (OAR's) were considered during the optimization of treatment plans. NTCP was calculated using LKB fractionated model. Multivariate regression analysis was performed to see the effect of EQD2Gy, NLV, and PTV on MLD2Gy.Results.A significant dosimetric difference was observed in the normal liver (liver-ITV/iGTV). A reduction of 1.7% in NTCP was observed from FB to BH technique. The leverage of dose escalation is more in BH because MLD2Gycorresponds to 5%, 10%, 20%, and 50% NTCP was 0.099 Gy, 0.41 Gy, 1.21 Gy, and 3.432 Gy more in BH as compared to FB technique. In MVRA, the major factor which was attributed to a change in MLD2Gyis EQD2Gy. Conclusion. From FB to BH technique, a significant reduction in NTCP was observed. The dose prescription is a major factor attributed to the change in MLD2Gy. Advances in knowledge: If feasible, prefer BH treatment either for tumor dose escalation or for the reduction in NTCP.