Retrospective study on efficacy and safety of nanoparticle paclitaxel and concurrent radiotherapy in patients with advanced head and neck cancer

Background: Advanced (Stage III and IV) Squamous Cell Carcinomas of the head and neck (SCCHN) produce severe functional impairment, considerable morbidity, and significant mortality. Over the past 2 decades, organ-sparing efforts using either induction chemotherapy or concurrent chemotherapy and radiotherapy (RT) have become popular and have demonstrated equivalent or superior survival rates compared with surgery and/or RT alone, with a survival rate of approximately 40% at 5 years. Although the addition of chemotherapy to RT enhances toxicity, randomized trials and meta analyses have documented improved survival clearly compared with the results from RT alone. Initially, most combinations included once-daily RT combined with cisplatin either alone or with 5-fluorouracil (5-FU). There was number of toxicities of high grades associated with these drugs, and also difficulty in their administration. We have retrospectively studied nanoparticle paclitaxel with RT on concurrent setting as an alternative.Methods: We have retrospectively studied  data of patients of advanced SCCHN treated with nanoparticle paclitaxel along with RT. Nanoparticle paclitaxel was administered at a dose of 80 mg/m2 over one hour infusion once weekly along with RT, 60 Gray (Gy) in 30 fractions, five days per week, over 6 weeks.Results: Total numbers of patient in this study were 28 with median age of 49 years. 78.57% of patient had stage IV disease and 21.43% stage III. Overall response rate was 68% with complete response (CR) in 29% and partial response (PR) in 39%.Conclusions: The use of nanoparticle paclitaxel along with RT is safe, feasible, efficacious and cost effective. Intensive randomized studies with large sample size are required in this direction.

A gravitational constant transition within cepheids as supernovae calibrators can solve the Hubble tension

Local universe measurements of the Hubble constant (H0) using SNe Ia with Cepheids as calibrators yield a value of H0 which is in tension with the value inferred from the CMB and other higher redshift probes. In ref. [1], the authors proposed a rapid transition in the value of the effective Newtonian gravitational constant G in order to alleviate the Hubble tension. The transition point was chosen so as to only affect distance estimates to Hubble flow SNe. However, in this study, the authors made the assumption that SNe Ia peak luminosity $L$ increases with Chandrashekhar mass $M_c$. This hypothesis contradicts a previous semi-analytic study of SN light curves in the presence of G-transition [2] which found that $L\propto M_c^{-0.97}$. Motivated by the results of refs. [1] and [2], we propose a hypothesis of a sudden recent change in the effective G at an epoch which corresponds to a look-back distance between $\sim$ 7 - 80 Mpc. A transition in G at these distances would affect both our estimate of the distances to Cepheids in calibrator galaxies, as well as to the Hubble flow supernovae. Upon fitting the observational data to this hypothesis, we find three interesting results: (i) we find mild evidence for a G-transition at 22.4 Mpc (73 million years ago) which is preferred (using certain estimators) by the calibrator type Ia SNe data over no G-transition, (ii) the H0 parameter inferred under this hypothesis is in good agreement with the value obtained from the CMB for a 4% larger value of G at earlier times, thus potentially resolving the Hubble tension, (iii) we obtain a fit to the scaling relationship between SN peak luminosity $L$ and Chandrasekhar mass $M_c$, as $L\propto M_c^{-1.68 \pm 0.68}$, which is in good agreement with the prediction of the theoretical study of ref. [2]. We also discuss how other probes could be used to verify this transition in the value of G.Comment: 23 pages, 1 figur

Post-operative wound infiltration with dexmedetomidine and magnesium sulphate as adjuvant to levobupivacaine for lumbar laminectomy: a prospective, double blinded, randomized controlled study

Background: Wound infiltration with local anaesthetic is safe and effective technique for providing postoperative analgesia following lumbar laminectomy. The objective of this study was to compare the efficacy of local wound infiltration on postoperative analgesia with levobupivacaine, levobupivacaine plus magnesium sulphate and levobupivacaine plus dexmedetomidine in patient undergoing lumbar laminectomy.Methods: Ninety adult patients were randomly allocated into three groups. After the completion of lumbar laminectomy, the drug was locally infiltrated into the paravertebral muscles on either side. Group L received 10 ml of 0.5% levobupivacaine plus 10 ml normal saline, group LM received 10 ml of 0.5% levobupivacaine plus 500 mg magnesium sulphate (1 ml) plus 9 ml normal saline, group LD received 10 ml of 0.5% levobupivacaine plus 50 µg dexmedetomidine (0.5 ml) plus 9.5 ml normal saline. Postoperative visual analogue scale (VAS) pain score at 0, 1, 2, 4, 6, 8, 12 and 24 hours, time to first rescue analgesic drug and its total dose, quality of recovery score (QoR) and side effects were noted.Results: Postoperative VAS was significantly higher in group L as compared to group LM and LD (p<0.05). The time to first rescue analgesic drug was significantly longer in group LD (11.07±7.20 hr) than group LM (6.20±2.64 hr) and group L (3.93±2.70 hr) (p<0.001). The QoR score was significantly better in group LD as compared to group LM and L postoperatively (<0.01).Conclusions: Addition of magnesium sulphate or dexmedetomidine to levobupivacaine for local wound infiltration demonstrated enhanced postoperative analgesia.

The effect of general anaesthesia versus conscious sedation in dosimetric distribution of intracavitary radiotherapy in cervical cancer patients

Background: Majority of Indian patients presents in locally advanced stage and most of them treated by combination of external teletherapy and intracavitary brachytherapy (ICRT). Because of deficient infrastructure, the waiting period is generally long at existing caner canters. Hence ICRT may be done in conscious sedation to treat more patients by avoiding time consuming general anaesthesia. The aim of this study is to know the effect of general anaesthesia vs. conscious sedation in dosimetric distribution in brachytherapy and its feasibility.Methods: Total 80 ICRT applications were randomized to general anaesthesia (GA) and conscious sedation (CS) groups. Fletcher suit type of applicators was used and dose delivery equipment was cobalt 60 high dose rate remote after loading brachytherapy unit. In CS group, injection midazolam 0.5-8mg (median 2.5mg) in the form of slow i.v. infusion was used along with antiemetic support.Results: Total 6 parameters were analyzed. e.g., Dose to point A1, Dose to point A2, Bladder max dose, Bladder mean dose, Rectal max dose and Rectal mean dose. The dose distribution was found similar both   groups and it did not depend on type of anaesthesia.Conclusions: The high volume centers of developing countries are most suitable candidate to opt conscious sedation to perform ICRT to treat more cancer cervix patients in same time frame

Cancer oesophagus: is sequential chemo radiation better in elderly patients or patients with severe dysphagia?

Background:This study was conducted to analyse the local control, regional control and toxicities of sequential versus concurrent chemo radiation in the patients of oesophageal cancer especially in elderly.Methods: A total of newly diagnosed 50 patients were randomized in concurrent and sequential arm. Two courses of 3 weekly chemotherapy (Cisplatin and 5-FU based) were given concurrently and three courses of same chemotherapy were given neoadjuvantly with EBRT (44 Gys) respectively in randomised arms. HDR-ICBT (2 fractions of 5 Gy) delivered after two weeks of completion of EBRT in both arm.Results: Concurrent arm had higher incidence of grade III+IV overall all toxicity especially in elderly patients or patients that presented with grade IV or higher dysphagia. Other haematological and non-haematological toxicities were equal in both arms. Complete response at both primary and mediastina was higher in concurrent arm but there was no statistically significant difference.Conclusions: Our data suggest that if a patient can tolerate the combination of chemotherapy and radiation, this approach offers superior results but at the cost of higher incidence of severe toxicities especially in patients with grade IV or higher dysphagia or elderly patients. So this group could be treated with sequential chemo radiation

Comparison of two different doses of dexmedetomidine (0.25 mcg/kg and 0.5 mcg/kg) in prolonging duration of spinal anaesthesia and postoperative analgesia in patients undergoing trans urethral resection of prostate: a prospective randomized double blinded study

Background: Trans urethral resection of prostate (TURP) under spinal anaesthesia (SAB) in elderly with associated cardio-pulmonary, endocrine or other co-morbidities induces detrimental physiological and psychological stress response to surgery and anaesthesia. Proper sedation during spinal anaesthesia can reduces this response. Aim of this study was to compare the characteristics of spinal block, hemodynamic changes, and postoperative analgesia, following administration of intravenous DMT (0.25 mcg/kg and 0.5 mcg/kg) in elderly patients undergoing TURP under SAB.Methods: Sixty-eight patients were randomly allocated to two groups of 34 patients each. After giving spinal anaesthesia patients received two different doses of dexmedetomidine intravenously; 0.25 mcg/kg (Group D25) and 0.50 mcg/kg (Group D50) respectively. Drugs were given slowly in dilution of 10ml normal saline. Patients were monitored for intraoperative haemodynamics, sensory and motor block characteristics and postoperative analgesia in terms of VAS (visual analogue scale) and first and total dose of rescue analgesic.Results: Mean value of lowest HR in Group D50 and D 25 was comparable (p=0.11) and time taken to achieve lowest HR was also comparable (p=0.13). Mean value of lowest SBP, DBP and MAP were lower in Group D50 than in Group D25 but the difference did not reach statistical significance (p=0.52,0.95 and 0.41 respectively). Onset of sensory block was comparable between the two groups, p=0.62. Maximum sensory block was achieved significantly earlier in Group D50 (10.64±2.75 min versus 12.94±3.04 min in Group D25), p=0.0012. Group D50 patients achieved Bromage score 3 earlier (10.735±1.797 min) than group D25 (12.794±2.52 min) (p=0.00). Recovery from motor block was found earlier in Group D25 group (141.325±4.97 mins) compared to Group D50 (154.41±8.143 mins). Group D50 reported significantly higher sedation than group D25 (p=0.00). Group D25 reported more pain at 4 hours compared to Group D50 (VAS -4.705±0.462 versus 2.588±1.478). Time of requirement of first rescue analgesia was delayed in Group D50 (270.59±50.78 mins) than in Group D25 (172.50±10.46 mins), p=0.000.Conclusions: Dexmedetomidine is effective in relieving anxiety in elderly patients undergoing TURP under spinal anaesthesia. Dose of 0.50 mcg/kg is more effective than 0.25 mcg/kg without increasing the risk of adverse effect.

Comparison of 2D and 3D gamma evaluation method in patient specific intensity-modulated radiotherapy quality assurance

Background: In this study we have compared 2D and 3D gamma pass percentage for a variety of acceptance criteria for 40 step-and-shoot IMRT (intensity-modulated radiotherapy) plans. Methods: Treatment planning was done for 40 patient including head and neck, abdomen and pelvis simulated on the Siemens Healthcare GmBH CT simulator with images of 3 mm slice thickness using treatment planning system (TPS) (Monaco Version 5.11.03, Elekta medical system) using Monte Carlo algorithm. The gamma evaluation was done using PTW VeriSoft 8.1 which allowed us to perform 2D and 3D gamma index calculation, slice-by-slice comparison of measured and calculated dose distributions, measured dose was compared against the calculated DICOMRT dose on the OCTAVIUS 3D phantom from TPS. Results: The average 3D and 2D gamma passing in coronal planes were 96.61±0.45% and 96.27±0.78% for 5 mm/5% criteria, 93.74±4.17% and 91.9±4.88% for 3 mm/3% criteria, 85.83±7.58% and 82.41±8.06% for 2 mm/2% criteria and 62.8±9.42% and 59.18±9.52% for 1 mm/1% criteria respectively for all cases. The average gamma passing rate for 3D gamma analysis was 0.35%, 1.97 %, 3.97% and 5.78% higher when compared with 2D coronal planar analyses for 5 mm/5%, 3 mm/3%, 2 mm/2% and 1 mm/1% DTA criteria respectively. Conclusions: It is concluded in the study that 3 D gamma passing rate is higher compared to 2D gamma passing for head and neck, abdomen and pelvis cases

ICAR: endoscopic skull‐base surgery

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Segmented HPGe detectors for post-irradiation examination of nuclear fuel : Design and demonstration in gamma emission tomography

Gamma emission tomography (GET) is a proven non-invasive technique for post-irradiation examination of nuclear fuel. In the past, collimated HPGe detectors were used for GET measurements due to their good energy resolution. However, because a large number of projections need to be acquired to achieve high spatial resolution, the use of a single HPGe detector is associated with long measurement times. This thesis investigates the use of an electrically segmented HPGe detector for GET, proposing two conceptual types of segments: 1) scattering segments, each aligned with a collimator slit for localisation, and 2) energy deposition segments for aiding in the full energy deposition. The feasibility of a true coaxial segmented detector for this application was studied using the Monte Carlo particle transport code MCNP. Performance parameters, such as detection efficiency and mislocalisation rate, were obtained using proposed analysis methods. Furthermore, the dimensions of the segmentation pattern of the 18 detection elements were optimised based on the detector's foreseeable use and the performance parameters. For the experimental demonstration, a scaled-down planar prototype detector consisting of 6 scattering segments and 1 energy deposition segment was designed, with a working principle similar to the proposed true coaxial detector. The spatial response of the collimated prototype detector was obtained using MCNP simulations. In the experimental evaluation, energy resolution in different operating modes, count rate capabilities, and mislocalisation rate were obtained. The detector was found 3 times faster than when used in an unsegmented mode upon comparing the simulation and experimental results concerning the relative detection efficiency. An experimental demonstration of the detector in the proposed application was successfully performed at the BETTAN tomography test bench at Uppsala University using three mockup fuel rods (filled with 137Cs source). Images were reconstructed using the filtered back projection algorithm on the projection data. Based on the experimental results, it is recommended to use such detectors for faster data acquisition combined with good energy resolution in GET, which in turn allows for improved spatial resolution in GET examinations of irradiated nuclear fuel