Background Sphingosine-1-phosphate (S1P) is a potent oncogenic lipid. Intracellular levels of S1P are tightly regulated by eight S1P-metabolizing enzymes. S1P synthesis is catalyzed by two sphingosine kinases, i.e., sphingosine kinase 1 (SphK1) and sphingosine kinase 2 (SphK2). Five lipid phosphatases (two S1P phosphatases and lipid phosphate phosphatases (LPPs) 1, 2, and 3) reversibly convert S1P back to sphingosine. Previously, we have determined the mRNA expression profile of eight S1P-metabolizing enzymes in tumor tissues and adjacent normal tissues from oral squamous cell carcinoma (OSCC) patients. Except for SphK1, the role of S1P-metabolizing enzymes in OSCC has been poorly studied. Methods We have determined the protein expression of four S1P-metabolizing enzymes (SphK1, SphK2, sphingosine-1-phosphate phosphatase 1 (SGPP1), and lipid phosphate phosphatase 3 (LPP3)) by immunohistochemistry (IHC) in tumor tissues of 46 OSCC patients. Six subjects with non-dysplastic oral mucosa were also included in the study. The immunoreactivity score (IRS) was calculated for each protein in every subject. Further, we determined the associations of expression of S1P-metabolizing enzymes with clinicopathological features of OSCC patients. Results We demonstrate the low IRS for SphK2 and LPP3 in OSCC tumors. Importantly, expression of SphK2 and LPP3 was downregulated in malignant epithelial cells compared to non-malignant mucosa. Further, LPP3 expression negatively correlated with tumor‑node‑metastasis (TNM) staging of patients (r = −0.307, p = 0.043). Importantly, expression of LPP3 in tumors was found to be an independent predictor of perinodal extension (b = −0.440, p = 0.009), lymphovascular invasion (b = −0.614, p < 0.001), lymph node ratio (b = 0.336, p = 0.039), and TNM staging (b = −0.364, p = 0.030). Conclusion Taken together, our data show that expression of SphK2 and LPP3 is decreased compared to normal mucosa. Thus, the S1P signaling pathway could represent a potential therapeutic target.

IntroductionRecently, the one-week hypofractionated radiotherapy regimen (26 Gy in 5 fractions) for adjuvant breast radiotherapy has been shown to be non-inferior to other hypofractionated regimens (15-16 fractions). The aim of the present dosimetric study is to compare Intensity Modulated Radiotherapy (IMRT), Volumetric Modulated Arc Therapy (VMAT) and 3D Conformal Radiotherapy (3D-CRT) for a one-week hypofractionated radiotherapy regimen (26 Gy in 5 fractions) for adjuvant breast radiotherapy. MethodsA total of 30 patients with histologically proven invasive carcinoma of the breast after breast conservation surgery (BCS) or modified radical mastectomy (MRM) were considered for in silico planning study. The dose prescription used was 26 Gy in 5 fractions as used in the FAST Forward protocol. Targets were contoured according to standard guidelines. The heart, ipsilateral lung, and contralateral breast were contoured as organs at risk. ResultsPlanning Target Volume (PTV) coverage: For IMRT, VMAT and 3D-CRT, respectively, the volumes that received at least 95% of the prescription dose (V 95 ) were 95.7 ± 2.12, 92.47 ± 3.83, 90.87 ± 5.13; mean PTV doses (D mean ) were 26.1 ± 0.6, 25.7 ± 0.7, and 28 ± 4.39 (3D-CRT has higher D mean compared to other techniques). Maximum PTV doses (D max ) were 28.23 ± 0.72, 28.73 ± 0.64, and 29.8 ± 1.03. IMRT had a better V 95 coverage and conformity index.Organs At Risk (OARs): The volumes that received at least 25% of the prescription dose (V 25 ) of the heart were 3.41 ± 4.7, 1.8 ± 2.02 and 4.3 ± 6.98 in IMRT, VMAT and 3D-CRT, respectively. The volumetric (V 25 ) comparison of heart dose in left-sided breast cancer was significantly different between VMAT and 3D-CRT (p=0.04, Wilcoxon signed-rank test). The volume that received at least 5% of the prescription dose (V 5 ) was less than 25% in the 3D-CRT plan (12.55).

Introduction: Breast cancer treated with adjuvant hypofractionation radiotherapy with two different techniques, i.e., volumetric-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) and their effects in terms of loco-regional control and adverse effects in terms of cutaneous, pulmonary, and cardiac outcomes are compared. Materials and methods: This is a prospective non-randomized observational study. VMAT and IMRT plan for 30 breast cancer patients who were supposed to receive adjuvant radiotherapy were prepared using a hypofractionation schedule. The plans were dosimetrically evaluated. Objective: Dosimetric comparative analysis of IMRT and VMAT in hypofractionated radiotherapy in breast cancer is done and tested whether VMAT has a dosimetric advantage over IMRT. These patients were recruited for a clinical assessment of toxicities. They were followed up for at least three months. Result: On dosimetric analysis, planning target volume (PTV) coverage (PTV_ V95 ) of both VMAT (96.41 ± 1.31) and IMRT (96.63 ± 1.56) were similar with significantly lower monitor units required with VMAT plans (1,084.36 ± 270.82 vs 1,181.55 ± 244.50, p = 0.043). Clinically, all patients tolerated hypofractionation through VMAT (n = 8) and IMRT (n = 8) satisfactorily in the short term. No cardiotoxicity or appreciable falls in pulmonary function test parameters were observed. Acute radiation dermatitis poses challenges similar to standard fractionation or any other delivery technique. Conclusion: PVT dose, homogeneity, and conformity indices were similar in both VMAT and IMRT groups. In VMAT, there was high-dose sparing of some critical organs like the heart and lungs at the cost of the low-dose baths to these organs. Increased risk of secondary cancer will require a decade-long follow-up study to indict the VMAT technique. As we move toward precision in oncology, “one-size-fits-all” can never be an acceptable dictum. Each patient is unique and therefore we must offer, and the patient must “choose wisely.”