Synthesis of Amino Acid-Based Cationic Lipids and Study of the Role of the Cationic Head Group for Enhanced Drug and Nucleic Acid Delivery.

Leveraging liposomes for drug and nucleic acid delivery, though promising due to reduced toxicity and ease of preparation, faces challenges in stability and efficiency. To address this, we synthesized cationic amphiphiles from amino acids (arginine, lysine, and histidine). Histidine emerged as the superior candidate, leading to the development of three histidine-rich cationic amphiphiles for liposomes. Using the hydration method, we have prepared the liposomes and determined the optimal N/P ratios for lipoplex formation via gel electrophoresis. In vitro transfection assays compared the efficacy of our lipids to Fugene, while MTT assays gauged biocompatibility across cancer cell lines (MDA-MB 231 and MCF-7). The histidine-based lipid demonstrated marked potential in enhancing drug and nucleic acid delivery. This improvement stemmed from increased zeta potential, enhancing electrostatic interactions with nucleic acids and cellular uptake. Our findings underscore histidine's crucial role over lysine and arginine for effective delivery, revealing a significant correlation between histidine abundance and optimal performance. This study paves the way for histidine-enriched lipids as promising candidates for efficient drug and nucleic acid delivery, addressing key challenges in the field.

Validation of a simple technique for accurate treatment delivery for bilateral breast irradiation using the electronic portal imaging device.

Background and Aims: While bilateral breast cancer is rare, the challenge for the radiation oncologist is to limit the dose to multiple important organs-at-risk and reducing the chance of overlapping tangential fields to limit hotspots. In this study, we present a simple technique to verify the setup accuracy of breast tangential fields using the electronic portal imaging device (EPID) for bilateral breast cancer. Patients and Methods: A 74-year-old female, with bilateral breast cancers, right staged as T1N0M0 and the left T2N1M0, received postoperative radiotherapy following bilateral breast conservative surgery. Standard CT-based simulation and target delineation were done, followed by treatment planning using classical field arrangements with two separate isocenters, one for each breast (keeping identical anteroposterior and superior-inferior coordinates). The planned doses were 45 Gy/25 # for whole breasts, plus tumor bed boost of 15 Gy/6 # and 50 Gy/25 # to left supraclavicular fossa. After setting up the patient, two small lead wires were placed at the medial borders of medial tangents (as seen on light fields) of each breast (longer one for left), followed by EPID imaging (dual exposure: One lateral tangent field image and other larger to include lead wires) of respective contralateral lateral tangential fields to verify that there was no actual overlapping with the opposite medial tangential field, as indicated by the lead wires. Conclusion: The study has validated a simple EPID-based technique for routine use in the field matching for radiotherapy of bilateral breast cancer.

Comparative performance analysis of 2D and 3D gamma metrics for patient specific QA in VMAT using Octavius 4D with 2D-Array 1500.

INTRODUCTION: Gamma pass percentage (GPP) is the predominant metric used for Patient Specific Quality Assurance (PSQA) in radiation therapy. The dimensionality of the measurement geometry in PSQA has evolved from 2D planar to 3D planar, and presently to state-of-the-art 3D volumetric geometry. We aim to critically examine the performance of the three-dimensional gammas vis-à-vis the older gamma metrics of lower dimensionality to determine their mutual fungibility in PSQA, using clinically approved Volumetric Arc Therapy (VMAT) plans. METHODS AND MATERIALS: Gamma pass percentages derived from PSQA for VMAT plans using Octavius 4D phantom with 2D-Array 1500 and its proprietary software were recorded. 2D planar, 3D planar, and 3D volumetric gamma pass percentages were retrospectively extracted for multiple treatment plans at three sites, using three acceptance limits, and for two modes of normalization. The differences in mean pass percentages, and the pairwise correlation between geometries were calculated within limits of statistical significance. RESULTS: A significant increase in mean pass rates was observed from 2D planar to 3D planar geometries. The difference was less pronounced from 3D planar to 3D volumetric. 2D planar v/s 3D planar showed a significant degree of correlation among themselves, which was not seen against most of the 3D volumetric pass rates. CONCLUSION: The mean gamma pass rates show conclusive evidence of the benefits of shifting from 2D planar to higher dimensions measurement geometries, but the benefits of using 3D volumetric compared to 3D planar is not always unequivocal. The correlations show mixed results regarding the interdependence of pass percentages at different geometries.

Clinical audit of dose-escalated radical radiotherapy for advanced cervical carcinoma using a pragmatic protocol (3 fractions of 8 Gy HDR brachytherapy).

INTRODUCTION: Recent image-guided brachytherapy data suggests, dose-escalation to a cumulative EQD2 (equivalent dose delivered at 2 Gy/#) of ≥87 Gy is associated with significantly better disease control. We present a clinical audit of a pragmatic radical radiotherapy protocol for advanced cervical cancer, using fewer fractions of brachytherapy than in the presently most popular protocol. MATERIAL & METHODS: Between July 2015 and December 2018, 96 consecutive advanced cervical carcinoma patients were treated by pelvic external beam radiotherapy (EBRT) (50 Gy/25fractions/5 weeks) ± weekly intravenous chemotherapy followed by image guided high dose rate (HDR) brachytherapy, using intracavitary/interstitial/hybrid techniques (intended point A dose: 8 Gy/fractions) × 3 fractions (cumulative target EQD2 ≥ 86 Gy). Insertion was done individually for each fraction of treatment. RESULTS: All patients completed their intended radiation protocol. 93.8% patients achieved complete response, while 6.2% patients achieved only partial response; no patients had stable/progressive disease. Out of the patients with partial response, 4.2% (4 out of 5 cases) cases of central/nodal residual disease underwent salvage surgery. At a median follow up of 21 months, 8.3% (8) patients had local failure, 1.1% (1) had nodal failure and 3.1% (3) had distant failures. Median Failure Free Survival was 29 months (26.5-31.5 months). On follow up, 6.3% and 3.2% patients had grade 2 or worse rectal and bladder morbidities respectively. CONCLUSION: The protocol under study has been safe and effective in achieving dose-escalated radical chemoradiation in advanced cervical carcinoma. The use of fewer insertions of brachytherapy is logistically easier & can also be expected to improve compliance.

Dosimetric analysis of Deep Inspiratory Breath-hold technique (DIBH) in left-sided breast cancer radiotherapy and evaluation of pre-treatment predictors of cardiac doses for guiding patient selection for DIBH.

INTRODUCTION: The risk of radiotherapy-associated cardiovascular disease has been a concern for decades in breast cancer survivors. The objective of our study is to evaluate the dosimetric benefit of Deep Inspiratory Breath-hold technique (DIBH) on organs-at-risk (OAR) sparing in left-sided breast cancer radiotherapy and to find out pre-treatment predictors of cardiac doses for guiding patient selection for DIBH. MATERIAL AND METHODS: Pre-radiotherapy planning CT scans were done in Free Breathing (FB) and in DIBH [using Active Breathing Coordinator system (ABC™)] in 31 left sided breast cancer patients. 3DCRT plans were generated for both scans. Comparison of anatomical and dosimetric variables were done using paired t test and correlation was evaluated using Pearson correlation. Linear regression was used to get independent predictors of cardiac sparing and Receiver Operating Characteristic (ROC) curve analysis was done to find out the specific threshold of the predictors. RESULTS: There was a 39.15% reduction in mean heart dose in DIBH compared to FB (2.4 Gy vs 4.01 Gy) (p < 0.001), 19% reduction in maximum Left Anterior Descending (LAD) dose and a 9.9% reduction in ipsilateral lung mean dose (p = 0.036) with DIBH. A significant correlation was observed between reduction in Heart Volume in Field (HVIF) and Maximum Heart Depth (MHD) with reduction in mean heart dose. Reduction in HVIF (ΔHVIF) independently predicted cardiac sparing. CONCLUSION: DIBH leads to significant reduction in OAR doses and is suggested for all patients of left-sided breast cancer undergoing radiotherapy. However, HVIF and MHD predicted for cardiac sparing and threshold criteria of ΔHVIF and ΔMHD may be used by centres with high workload to select patients for DIBH.

Choosing a career in radiation oncology in India: A survey among young radiation oncologists.

BACKGROUND: Radiation oncology in India is much debated as a career option to take up. This survey among young radiation oncologists (YROs), the first of its kind, attempts to assess the career expectations and concerns that affect most of us. MATERIALS AND METHODS: This survey was conducted using the online survey tool of SurveyMonkey in October 2018. The Association of Radiation Oncologists of India (AROI) members' database was used to send the survey link over E-mail to recipients (AROI life member after 2004). RESULTS: Out of 1685 invitees, 492 (29.19%) recipients took the survey. Most (69.14%) of the respondents were males who worked as senior residents and junior consultants and employed in private hospitals and state-level teaching institutes. Postspecialization (MD/DNB) experience was mostly <3 years (56.52%). Most of YROs worked in Tier-I city (48.9%) mostly in telecobalt-based facilities. Most of our respondents (73.01%) aspired to work in academic teaching hospital/research institute, and the primary concern was academics/research (39.88%) followed by income (23.31%). There was a similar distribution of respondents with respect to their desire to shift to medical oncology. There was marked dissatisfaction over remuneration, job openings, job security, and poor scope of career improvement. 56.50% of respondents believed that they need to move abroad to improve their quality of life. However, 76.69% of respondents still felt very passionate about their professional choice. Finally, 61.97% of professionals believed that this survey will correctly reflect the present scenario among YROs. CONCLUSIONS: The survey portrays a mixed picture as expected. Major policy changes are required to improve the infrastructure and job opportunities of this profession.

Retrospective study on performance of constancy check device in Linac beam monitoring using Statistical Process Control.

AIM: To examine the application of Statistical Process Control (SPC) and Ishikawa diagrams for retrospective evaluation of machine Quality Assurance (QA) performance in radiotherapy. BACKGROUND: SPC is a popular method for supplementing the performance of QA techniques in healthcare. This work investigates the applicability of SPC techniques and Ishikawa charts in machine QA. MATERIALS AND METHODS: SPC has been applied to recommend QA limits on the particular beam parameters using the QUICKCHECK webline QA portable constancy check device for 6 MV and 10 MV flattened photon beams from the Elekta Versa HD linear accelerator (Linac). Four machine QA parameters - beam flatness, beam symmetry along gun target direction and left-right direction, and beam quality factor (BQF) - were selected for retrospective analysis. Shewhart charts, Exponentially Weighted Moving Average (EWMA) charts and Cumulative Sum (CUSUM) charts were obtained for each parameter. The root causes for a failure in machine QA were broken down into an Ishikawa diagram enabling the user to identify the root cause of error and rectify the problem subsequently. RESULTS: Shewhart charts and EWMA charts applied could detect loss in control in one variable in the 6 MV beams and in all four variables in 10 MV beams. CUSUM charts detected offsets in the readings. The Ishikawa chart exhaustively included the possible errors that lead to loss of control. CONCLUSION: SPC is proven to be effective for detection of loss in control in machine QA. The Ishikawa chart provides the set of probable root causes of machine error useful while troubleshooting.

MAP Kinase driven actomyosin rearrangement is a crucial regulator of monocyte to macrophage differentiation.

Rearrangement of actin cytoskeleton correlates significantly with the immune responses as the perturbation of cytoskeletal dynamics leads to many immune deficiencies. Mechanistic insights into this correlation remain unknown. Cellular spreading, the most characteristic phenotype associated with monocyte to macrophage differentiation, led us to investigate the contribution of actomyosin dynamics in monocyte differentiation. Our observation revealed that actomyosin reorganization intrinsically governs the process of monocyte to macrophage differentiation. Further, we established that the MAPK-driven signaling pathways regulate the cellular actomyosin dynamics that direct monocyte to macrophage differentiation. We also identified P42/44 Mitogen-Activated Protein Kinase (P42/44 MAPK), P38 Mitogen-Activated Protein Kinase (P38 MAPK), MAP Kinase Activated Protein Kinase 2 (MK-2), Heat Shock Protein 27 (Hsp-27), Lim Kinase (Lim K), non-muscle cofilin (n-cofilin), Myosin Light Chain Kinase (MLCK) and Myosin Light Chain (MLC) as critical components of the signaling network. Moreover, we have shown the involvement of the same signaling cascade in 3D gel-like microenvironment induced spontaneous monocyte to macrophage differentiation and in human blood-derived PBMC differentiation. Our study reveals new mechanistic insights into the process of monocyte to macrophage differentiation.

Protease-activated receptor 2 promotes actomyosin dependent transforming microvesicles generation from human breast cancer.

Apart from blood coagulation, coagulation proteases are involved inextricably in cancer progression/propagation via intra/inter-cellular signaling, mediated predominantly by protease-activated receptors (PARs). Microvesicles (MVs), a plasma membrane shredded component, has recently been identified as an important contributor to human breast cancer metastasis. However, the role of PAR2 in promoting MVs generation from breast cancer cells remains largely unexplored. The objective of this study is to investigate whether coagulation protease-mediated human breast cancer propagation commences via MVs and also to decipher the underlying signaling mechanism. Here, we elicited that coagulation factor-FVIIa and Trypsin activates PAR2, which governs MVs shedding from MDAMB231 cells by altering actomyosin dynamics. Treatment of cells with PAR2 activators facilitate MVs generation by activating three independent (MAPK, P38, and Rho) signaling cascades. MAPK, signals through activating MLCK followed by MLC phosphorylation to alter myosin organization whereas, P38 reorganizes actin dynamics by the sequential activation of MK2 and HSP27. RhoA-dependent ROCK-II activation again contributes to remodeling myosin II activity. Further, both our in vitro and in vivo analyses showed that these MVs potentiate invasive and migratory property to the recipient cells. Breast cancer patients blood show an elevation of TF-bearing, pro-metastatic MVs than normal. These findings give an insight into the detailed signaling mechanism involved in the production of MVs with transforming ability from PAR2-activated human breast cancer cells. Understanding these mechanistic details will certainly help to identify crucial targets for therapeutic interventions in MVs-associated human breast cancer metastasis.

Synthesis of Phosphatidylserine and Its Stereoisomers: Their Role in Activation of Blood Coagulation.

Natural phosphatidylserine (PS), which contains two chiral centers, enhances blood coagulation. However, the process by which PS enhanced blood coagulation is not completely understood. An efficient and flexible synthetic route has been developed to synthesize all of the possible stereoisomers of PS. In this study, we examined the role of PS chiral centers in modulating the activity of the tissue factor (TF)-factor VIIa coagulation initiation complex. Full length TF was relipidated with phosphatidylcholine, and the synthesized PS isomers were individually used to estimate the procoagulant activity of the TF-FVIIa complex via a FXa generation assay. The results revealed that the initiation complex activity was stereoselective and had increased sensitivity to the configuration of the PS glycerol backbone due to optimal protein-lipid interactions.

Coagulation factor VIIa-mediated protease-activated receptor 2 activation leads to ß-catenin accumulation via the AKT/GSK3ß pathway and contributes to breast cancer progression.

Cell migration and invasion are very characteristic features of cancer cells that promote metastasis, which is one of the most common causes of mortality among cancer patients. Emerging evidence has shown that coagulation factors can directly mediate cancer-associated complications either by enhancing thrombus formation or by initiating various signaling events leading to metastatic cancer progression. It is well established that, apart from its distinct role in blood coagulation, coagulation factor FVIIa enhances aggressive behaviors of breast cancer cells, but the underlying signaling mechanisms still remain elusive. To this end, we investigated FVIIa's role in the migration and invasiveness of the breast cancer cell line MDA-MB-231. Consistent with previous observations, we observed that FVIIa increased the migratory and invasive potential of these cells. We also provide molecular evidence that protease-activated receptor 2 activation followed by PI3K-AKT activation and GSK3ß inactivation is involved in these processes and that ß-catenin, a well known tumor-regulatory protein, contributes to this signaling pathway. The pivotal role of ß-catenin was further indicated by the up-regulation of its downstream targets cyclin D1, c-Myc, COX-2, MMP-7, MMP-14, and Claudin-1. ß-Catenin knockdown almost completely attenuated the FVIIa-induced enhancement of breast cancer migration and invasion. These findings provide a new perspective to counteract the invasive behavior of breast cancer, indicating that blocking PI3K-AKT pathway-dependent ß-catenin accumulation may represent a potential therapeutic approach to control breast cancer.

Living with the Elekta Compact: Limitations and ways around them.

Elekta AB, Sweden has recently propagated the Elekta Compact--a low-cost, small-footprint, single energy (6MV), linear accelerator, in India. The absence of electron beams and the inability to seamlessly deliver inverse planned intensity modulated radiotherapy (IMRT) segments, mean that some out-of-the-box thinking is mandatory for the full range of required treatments in different clinical settings, but is ultimately very rewarding. Our department started off in July 2011, with the Elekta Compact, equipped with MLCi2 and a camera-based electron portal imaging device. For head-neck cancers, we have successfully utilized a 3D conformal class-solution of eight-to-nine oblique beams, with multiple segments, to deliver an adequate dose to the posterior neck, respecting spinal cord tolerance. Parotid gland sparing is possible in selected node-negative hypopharyngeal/laryngeal cancers. For prostate cancers, we have developed a forward-planned IMRT protocol to routinely deliver 76-80 Gy to the prostate, with margins, while conforming to the same rectal dose-volume constraints as in inverse IMRT. Response and tolerance have been excellent so far. In head-neck cancers, the majority (71%) of patients was locally advanced; however, complete response was achieved in 75% of the cases. Grade 3 acute toxicities were seen in only 7% of the cases and compliance overall was excellent, with no patients requiring a gap in treatment. We achieved biochemical control in 100% of the prostate cancer patients; no patients had grade 3 acute toxicities, and with a median follow-up of 12 months, have yet to see any late rectal bleeding. Although engineered for simplicity and versatility, the Compact requires some innovative thinking by clinicians/physicists to optimize the full range of its possibilities. However, upgrades like inverse IMRT delivery, which are in the pipeline, are urgently needed for it to be viable, especially in a single-accelerator department.

Adaptive radiation therapy for pediatric head and neck malignancies: Dosimetric implications.

PURPOSE: This study was designed to evaluate the role of adaptive radiation therapy for children receiving curative radiation therapy to the head and neck region. METHODS AND MATERIALS: Ten children receiving definitive, conformal radiation therapy to the head and neck region were prospectively evaluated for anatomic changes during the course of radiation therapy. Images were acquired midway through the number of planned radiation therapy fractions during the planned course of radiation therapy. Body contours, target volumes, and organs at risk were redrawn on the new set of images. Two sets of additional treatment plans were generated: (1) a nonoptimized plan (plan 2), that is, an overlay of the original plan (plan 1) on the new set of contours, and (2) an optimized plan (plan 3) with the new set of contours. These 3 sets of plans were then compared for dosimetric differences. RESULTS: Five children had nasopharynx carcinoma, whereas the other 5 had embryonal rhabdomyosarcoma. The average reduction in gross tumor volume was 40% (mean volume, 41.87 mL; P = .005). The average changes in right and left parotid volumes were 2.72 and 1.92 mL, respectively. With nonoptimized plans, the average increase in maximum dose to the spinal cord was 15% (79.99%-94.99%; P = .013). With reoptimization, the maximum dose to the spinal cord decreased from 94.99% to 85.26% (mean difference, -9.73%; P = .02). Average D99 for the planning target volume (dose received by 99% of the target volume) was 88.66% and 86.89% with the original and reoptimized plans, respectively (P = .50). For the entire group, the mean conformation number index with nonoptimized plans was reduced from 0.734 to 0.628 (P = .013). This improved with reoptimization (P = .114). The homogeneity index improved with reoptimization from a mean value of 0.113 to 0.098 (P = 0.28). For nonoptimized plans, the average integral dose increased from 74.66 to 76.27 L-Gy (P = .486) compared with the original plans. Reoptimization resulted in a 5% average reduction in the integral dose, from 76.27 to 72.28 L-Gy (P = .007). CONCLUSIONS: This study demonstrates the usefulness of adaptive radiation therapy for children receiving radiation therapy to the head and neck region.

Helical tomotherapy-based hypofractionated radiotherapy for prostate cancer: a report on the procedure, dosimetry and preliminary clinical outcome.

CONTEXT: Hypofractionated intensity-modulated radiotherapy (IMRT) under image guidance using helical tomotherapy for prostate cancer improves therapeutic ratio. AIMS: To report on clinical and dosimetric experience using hypofractionated helical tomotherapy for prostate cancer. SETTINGS AND DESIGN: Prospective consecutive case series as feasibility study approved by Institutional Review Board (IRB) (2007-11). MATERIALS AND METHODS: The staging work-up, risk stratification, simulation, contouring, planning, online matching and treatment delivery methodology are described in detail. The doses to (prostate and nodal) PTV and organs at risk (bladder, rectum, bowel and femoral heads) are described. The audit of online matching was used to determine set-up errors, PTV margins and resultant translational vector. We also report the outcomes in terms of biochemical relapse-free survival and acute toxicity. RESULTS: Fifty-three consecutive patients were included. The baseline PSA was 23 ng/ml (1.60-100.37). The prostate BED3 ranged from 110-129 Gy (α/ß for prostate 1.5-3 Gy) and nodal 72-87.68 Gy. The required PTV margin by van Hark's formula for lateral, longitudinal and vertical axes were 11.30, 9.95 and 13.49 mm, respectively with resultant vectors 3-15 mm. There was 7% to 8% chance of missing part of CTV in absence of image guidance. There was only one patient requiring premature conclusion at 45 Gy due grade 3 genitourinary toxicity. At median follow-up of 23 months, biochemical relapse-free survival rate is 95.2%. CONCLUSIONS: Hypofractionated IMRT under image guidance using helical tomotherapy for prostate cancer is feasible with acceptable acute toxicity and may be advantageous in high throughput centers.

Prognostic factors and outcome in Askin-Rosai tumor: a review of 104 patients.

PURPOSE: To evaluate the prognostic factors and treatment outcome of patients with Askin-Rosai tumor of the chest wall treated at a single institution. METHODS AND MATERIALS: Treatment comprised multiagent chemotherapy and local therapy, which was either in the form of surgery alone, radical external-beam radiotherapy (EBRT) alone, or a combination of surgery and EBRT. Thirty-two patients (40%) were treated with all three modalities, 21 (27%) received chemotherapy and radical EBRT, and 19 (24%) underwent chemotherapy followed by surgery only. RESULTS: One hundred four consecutive patients aged 3-60 years were treated at the Tata Memorial Hospital from January 1995 to October 2003. Most (70%) were male (male/female ratio, 2.3:1). Asymptomatic swelling (43%) was the most common presenting symptom, and 25% of patients presented with distant metastasis. After a median follow-up of 28 months, local control, disease-free survival, and overall survival rates were 67%, 36%, and 45%, respectively. Median time to relapse was 25 months, and the median survival was 76 months. Multivariate analysis revealed age ≥18 years, poor response to induction chemotherapy, and presence of pleural effusion as indicators of inferior survival. Fifty-six percent of patients with metastatic disease at presentation died within 1 month of diagnosis, with 6-month and 5-year actuarial survival of 14% and 4%, respectively. CONCLUSION: Primary tumor size, pleural effusion, response to chemotherapy, and optimal radiotherapy were important prognostic factors influencing outcome. The combination of neoadjuvant chemotherapy, surgery, and radiotherapy resulted in optimal outcome.

Portal dosimetry for pretreatment verification of IMRT plan: a comparison with 2D ion chamber array.

Portal dosimetry (PD) was performed for 181 fields from 14 IMRT plans of various clinical sites at gantry zero and source-to-detector distance (SDD) of 100 cm. PD was realized using aSi1000 electronic portal imaging device (EPID) and portal dose prediction (PDP) algorithm implemented in Eclipse treatment planning system (TPS). Agreement of PDP predicted and EPID measured photon fluence/dose distribution were evaluated using gamma (γ) index set at 3% at 3 mm distance to point agreement (DTA). Three gamma scaling parameters, maximum γ (γ(max)), average γ (γ(avg)) and percentage of points with γ ≤ 1 (γ% ≤ 1) were estimated for each field. An independent measurement was carried out using MatriXX 2D ion chamber array with detector plane at 100 cm and γ(max), γ(avg) and γ% ≤ 1 were estimated using OmniPro IMRT analyzing software. Effect of extended SDD and gantry rotation on portal dosimetry outcome was also investigated for another 45 IMRT fields. PDP predicted and EPID measured photon fluence agrees well with overall mean values of γ(max), γ(avg) and γ% ≤ 1 at 2.02, 0.24 and 99.43%, respectively. γ(max) value was lower in 15 MV compared to 6 MV IMRT plan. Independent verification using MatriXX showed comparable overall mean values of γ(avg) and γ% ≤ 1 at 0.25 and 99.80%. However, in all plans, MatriXX showed significantly lower γ(max) (p < 0.05) with an overall mean value of 1.35. In portal dosimetry, compared to gamma values at 100 cm SDD, γ(max), γ(avg) and γ% ≤ 1 values improve from a mean of 0.16, 0.03 and 0.26 at 110 cm SDD to 0.35, 0.05 and 0.29 at 140 cm SDD. PD outcome was independent of gantry rotation. In conclusion, both MatriXX 2D ion chamber array and portal dosimetry showed comparable results and can be use as an alternative to each other for relative photon fluence verification.

Prognostic factors and outcome analysis of submandibular gland cancer: a clinical audit.

PURPOSE: To retrospectively review a long-term, single-institution experience of subjects with submandibular gland malignancies treated with definitive locoregional therapy with an aim to identify clinicopathologic variables that correlate with outcomes. MATERIALS AND METHODS: A comprehensive chart review of 47 patients presenting to the institute from 1993 to 2005 with a histologic diagnosis of submandibular salivary gland cancer was performed to extract demographic data, clinicopathological characteristics, and treatment details. Clinical and pathologic factors were correlated with locoregional control, distant metastases free survival, and disease-free survival using log-rank test and Cox proportional hazards model for univariate and multivariate analysis, respectively. RESULTS: With a median follow-up of 29 months (interquartile range, 13 to 64 months), the actuarial 5-year locoregional control, distant metastasis-free survival, and disease-free survivals of the entire cohort were 80.5%, 86.1%, and 71.8%, respectively. Overall stage grouping (P = .008), perineural invasion (P = .04), and radiotherapy dose (P = .033) were significant predictors of locoregional control. Overall stage grouping (P = .014) and T stage (P = .05) also affected disease-free survival. Extraglandular involvement showed a trend toward poorer outcome. CONCLUSIONS: Submandibular gland cancer is a rare disease with histologic diversity and variable clinical behavior. Overall stage grouping and perineural invasion remain the most significant predictors of outcome. Adequate doses of adjuvant radiotherapy improve locoregional control in high-risk patients.

Impact of radiation dose on locoregional control and survival on squamous cell carcinoma of anal canal.

PURPOSE: To perform a systematic analysis of clinical data of presentation, treatment, outcome, toxicity, survival and other associated prognostic factors of the patients of anal canal who received treatment at our hospital. METHODS AND MATERIALS: The medical records of 257 patients treated with radiotherapy with or without chemotherapy from the year 1985 to 2005 were studied. RESULTS: Median follow-up was 36months. Complete clinical response after radiotherapy was 74.4% in the whole group. The 5years overall (OAS) and disease-free (DFS) survival for the whole group was 71.5% and 61%, respectively. Patients with T1-2 tumors which received the radiation dose between 55 and 60Gy had superior locoregional control, DFS and OAS. Similarly T3-4 tumors receiving radiation dose more than 60Gy independently improved the locoregional control, DFS and OAS irrespective of the nodal status and addition of chemotherapy. CONCLUSIONS: Radiation dose of 56-60Gy for T1 and T2 and 65Gy for T3 and T4 tumors along with concurrent chemotherapy is required to achieve better local control, disease-free survival and overall survival, with acceptable toxicity.