Asymmetrically Coordinated Heterodimetallic Ir-Ru System: Synthesis, Computational, and Anticancer Aspects.

Herein, we present an unprecedented formation of a heterodinuclear complex [{(ppy)2IrIII}(µ-phpy){RuII(tpy)}](ClO4)2 {[1](ClO4)2} using terpyridyl/phenylpyridine as ancillary ligands and asymmetric phpy as a bridging ligand. The asymmetric binding mode (N∧N-∩-N∧N∧C-) of the phpy ligand in {[1](ClO4)2} is confirmed by 1H, 13C, 1H-1H correlated spectroscopy (COSY), high-resolution mass spectrum (HRMS), single-crystal X-ray crystallography techniques, and solution conductivity measurements. Theoretical investigation suggests that the highest occupied molecular orbital (HOMO) and the least unoccupied molecular orbital (LUMO) of [1]2+ are located on iridium/ppy and phpy, respectively. The complex displays a broad low energy charge transfer (CT) band within 450-575 nm. The time-dependent density functional theory (TDDFT) analysis suggests this as a mixture of metal-to-ligand charge transfer (MLCT) and ligand-to-ligand charge transfer (LLCT), where both ruthenium, iridium, and ligands are involved. Complex {[1](ClO4)2} exhibits RuIIIrIII/RuIIIIrIII- and RuIIIIrIII/RuIIIIrIV-based oxidative couples at 0.83 and 1.39 V, respectively. The complex shows anticancer activity and selectivity toward human breast cancer cells (IC50; MCF-7: 9.3 ± 1.2 µM, and MDA-MB-231: 8.6 ± 1.2 µM) over normal breast cells (MCF 10A: IC50 ≈ 21 ± 1.3 µM). The Western blot analysis and fluorescence microscopy images suggest that combined apoptosis and autophagy are responsible for cancer cell death.

Dosimetric Comparison of Robotic and Linear Accelerator Multi-Leaf Collimator-Based Stereotactic Radiosurgery for Arteriovenous Malformation.

PURPOSE: To investigate the dosimetric comparison of different collimators which are used in robotic radiosurgery (cyberknife-CK) and linear accelerator (LINAC) for stereotactic radiosurgery (SRS) in arteriovenous malformation (AVM). MATERIALS AND METHODS: Twenty-five AVM patients were planned in CK using FIXED cone, IRIS collimator, and multi-leaf collimator (MLC) based in LINAC. Dosimetric comparison was performed using Paddick conformity index (CIPaddick) and International Commission on Radiation Units and measurements (ICRU) homogeneity index (HIICRU), gradient score (GS), normal brain dose received by 10cc (D10cc) and critical structure (brain stem, optic chiasma, optic nerves) doses. Paired sample t-test was used for statistical analysis. RESULTS: Mean treatment volume was 3.16cc (standard deviation ± 4.91cc). No significant deviation (P =0.45, 0.237 for FIXED vs. IRIS and FIXED vs. MLC, respectively) was found in target coverage. For CIPaddick, the mean difference (MD) between FIXED- and MLC-based plans was 0.16(P = 0.001); For HIICRU, difference between FIXED and IRIS was insignificant (0.5, P = 0.823); but, when FIXED versus MLC, the deviation was 7.99% (P = 0.002). In FIXED- and MLC-based plans, significant difference was found in GS70 and GS40 (P < 0.041 and 0.005, respectively). MD between FIXED- and MLC-based plans for normal brain for 5Gy, 10Gy, 12Gy, and 20Gy were 36.08cc (P = 0.009), 7.12cc (P = 0.000), 5.84cc (P = 0.000) and 1.56cc (P = 0.000), respectively. AVM volume <0.7cc should be treated with CK FIXED and >0.7cc were treated by using FIXED or IRIS collimators. AVM volume > 1.4cc can be treated by either LINAC MLC-based SRS or CK. CONCLUSION: Our study shows CK collimator (IRIS and FIXED) could be able to treat brain AVMs in any size. Linac MLC-based SRS has some limitations in terms of conformity and low-dose spillage, and advantages like reduced treatment time and MU.

Artificial intelligence in brachytherapy: a summary of recent developments.

Artificial intelligence (AI) applications, in the form of machine learning and deep learning, are being incorporated into practice in various aspects of medicine, including radiation oncology. Ample evidence from recent publications explores its utility and future use in external beam radiotherapy. However, the discussion on its role in brachytherapy is sparse. This article summarizes available current literature and discusses potential uses of AI in brachytherapy, including future directions. AI has been applied for brachytherapy procedures during almost all steps, starting from decision-making till treatment completion. AI use has led to improvement in efficiency and accuracy by reducing the human errors and saving time in certain aspects. Apart from direct use in brachytherapy, AI also contributes to contemporary advancements in radiology and associated sciences that can affect brachytherapy decisions and treatment. There is a renewal of interest in brachytherapy as a technique in recent years, contributed largely by the understanding that contemporary advances such as intensity modulated radiotherapy and stereotactic external beam radiotherapy cannot match the geometric gains and conformality of brachytherapy, and the integrated efforts of international brachytherapy societies to promote brachytherapy training and awareness. Use of AI technologies may consolidate it further by reducing human effort and time. Prospective validation over larger studies and incorporation of AI technologies for a larger patient population would help improve the efficiency and acceptance of brachytherapy. The enthusiasm favoring AI needs to be balanced against the short duration and quantum of experience with AI in limited patient subsets, need for constant learning and re-learning to train the AI algorithms, and the inevitability of humans having to take responsibility for the correctness and safety of treatments.

Phase I/II Study of Extreme Hypofractionated Stereotactic Body Radiation Therapy Boost to Prostate for Locally Advanced, Node-Positive and Oligometastatic Cancer.

INTRODUCTION:  Stereotactic body radiation therapy (SBRT) is increasingly being utilized to deliver escalated radiation doses for improving outcomes in various malignancies. We analyzed our cohort of locally advanced, node-positive, and bone oligometastatic prostate cancer patients, that were treated with a combination of pelvic RT using conventional fractionation (CF) and SBRT boost to prostate using extreme hypofractionation (EH), along with hormone therapy (HT). MATERIALS AND METHODS:  Outcomes of 44 prospectively treated patients were analyzed. Volumetric modulated arc therapy (VMAT) was utilized to deliver a dose of 45 Gy to pelvic nodal region, 50 Gy to prostate, and 54-56 Gy to gross nodes in 25 fractions. EH boost 18 Gy in three fractions was delivered to the prostate using CyberKnife (Accuray, Sunnyvale, CA, USA) SBRT. Bone oligometastasis, if any, were treated to a dose of 16 Gy in two fractions, delivered on weekends. Serum prostate-specific antigen (PSA), multi-parametric magnetic resonance imaging (MRI) of pelvis, and prostate-specific membrane antigen-positron emission tomography (PSMA-PET) were used for response assessment during follow-up. HT was given as per standard guidelines. RESULTS:  There were 33 (75%) locally advanced, nine (20.5%) node-positive, and two (4.5%) oligometastatic cases. At a median follow-up of 63.5 months, the five-year progression-free survival (PFS) was 88.2%, biochemical PFS (bPFS) was 91.4% and overall survival (OS) was 96.9%. Grade III or greater acute genitourinary and gastrointestinal toxicity was 2.3% each, and late toxicity was 4.5% and 0%, respectively. CONCLUSION:  Excellent five-year outcomes can be attained even for locally advanced, node-positive and bone oligometastatic prostate cancer, by means of dose-escalation using EH-SBRT boost to the prostate.

Rare Malignancies in Eastern India, Socio-Economic Impact.

The etiology of cancer is multifactorial. Various factors, including physical carcinogens, chemicals and viral carcinogens affect patients with known predisposing factors who subsequently develop malignancies. Here is a retrospective study of 18 patients who developed rare malignancies in clinical situations like xeroderma pigmentosum, tuberous sclerosis, neurofibromatosis, hereditary multiple exostosis, second malignancies due to radiotherapy and chronic irritation. The predisposing factors like chronic infection in leprosy, filariasis, poverty and ignorance leading to the chronicity of the lesion, lack of available health care facilities and socio-cultural background, i.e. consanguinity marriage in some community are responsible for the development of these rare malignancies. They were treated at A.H Regional Cancer Centre, Cuttack, Odisha, which is located at Eastern part of India for various malignancies, between January 1989 and January 2008. Malignancies that developed in patients with the above predisposing factors are being reported here due to their rarity and to highlight the impact of socio cultural background in developing these malignancies. Patients with above clinical situations should be kept under close observation for early detection of malignancy so their chances of survival can be improved. In addition, those oncogenic stimuli that initiated or propagated the malignancies, due to socio-economic factors, should be addressed promptly to prevent their eventual development.

Mixed Germ Cell Tumor of Testis with Isolated Scapular Metastasis: A Case Report and Review of the Literature.

Bone metastasis is a rare entity in germ cell tumor of testis and is a poor prognostic site. It is usually associated with synchronous metastasis at other sites. Till now very few cases of isolated bone metastasis of germ cell tumor of testis have been reported but none have reported scapular metastasis. We are reporting a case of nonseminomatous germ cell tumor of right testis that was operated eight months ago and now presented with isolated scapular metastasis. Histopathology of the scapular tissue revealed rhabdomyosarcoma or poorly differentiated synovial sarcoma. Immunohistochemistry with serum markers concluded it to be metastatic germ cell tumor. To the best of our knowledge this is the first reported case of scapular metastasis of testicular germ cell tumor. This case is being reported here due to dilemmatic way of presentation and also to emphasize that histopathology may sometimes misguide and immunohistochemistry is necessary in such cases.