Human papillomavirus (HPV) genome status & cervical cancer outcome--A retrospective study.

BACKGROUND & OBJECTIVES: Persistent infections with high-risk (HR) human papillomaviruses such as HPV 16, 18, 31, 33 and 45 have been identified as the major aetiological factor for cervical cancer. The clinical outcome of the disease is often determined by viral factors such as viral load, physical status and oncogene expression. The aim of the present study was to evaluate the impact of such factors on clinical outcome in HPV16 positive, locally advanced cervical cancer cases. METHODS: One hundred and thirty two pretreatment cervical tumour biopsies were selected from patients undergoing radiotherapy alone (n=63) or concomitant chemo-radiation (n=69). All the samples were positive for HPV 16. Quantitative real time-PCR was carried out to determine viral load and oncogene expression. Physical status of the virus was determined for all the samples by the ratio of E2 copies /E7 copies ; while in 73 cases, the status was reanalyzed by more sensitive APOT (amplification of papillomavirus oncogene transcripts) assay. Univariate analysis of recurrence free survival was carried out using Kaplan-Meier method and for multivariate analysis the Cox proportional hazard model was used. RESULTS: The median viral load was 19.4 (IQR, 1.9- 69.3), with viral integration observed in 86 per cent cases by combination of the two methodologies. Both univariate and multivariate analyses identified viral physical status as a good predictor of clinical outcome following radiation treatment, with episomal form being associated with increased recurrence free survival. INTERPRETATION & CONCLUSIONS: The present study results showed that viral physical status might act as an important prognostic factor in cervical cancer.

Evaluation of interobserver and interscale agreement in assessing late bowel toxicity after pelvic radiation in patients with carcinoma of the cervix.

BACKGROUND: Lack of agreement and inconsistency in capturing late bowel toxicity may be a source of error while reporting trials with toxicity endpoints. Documenting baseline inconsistency while scoring toxicity questionnaires (RTOG/EORTC and CTCAE) may be worthwhile. The present study was conducted as a quality assurance measure prior to initiating a randomized trial (PARCER; NCT01279135) that evaluates the impact of image-guided radiation on bowel toxicity. METHODS: From August 2010 to July 2011, patients with cervical cancer who underwent pelvic chemoradiation >6 months ago, with controlled disease and any bowel symptom at follow-up, were included. RTOG and CTCAE questionnaires were filled by two blinded observers. Interscale (RTOG vs CTCAE) and interobserver (observer A and B) agreement were evaluated with Spearman's correlation and kappa statistic. RESULTS: Fifty-five patients were included. Twelve patients with symptoms could not be graded by the RTOG scale. Of those graded as asymptomatic on RTOG, distension, vomiting, pain and nausea were identified as the most common symptoms. Amongst these, grade 1, 2 and 3 toxicity was observed in 6, 5 and 1 patient, respectively. The interscale correlation was moderate (Spearman's correlation ρ = 0.56; P = 0.001). High interobserver agreement (92%) was observed within the RTOG scale [kappa (κ) -0.94; 95% CI 0.77-1]. All disagreements were observed while scoring grade 1-2 toxicity. Among CTCAE, agreement was lower with modules such as distension, anorexia, nausea and constipation. CONCLUSIONS: High interobserver agreement was observed for both RTOG and most CTCAE subscales; most disagreements were for grade 1-2. Interscale agreement (RTOG and CTCAE) was moderate. Detailed patient interrogation or use of patient-reported-outcome scores while documenting the aforesaid subscales may be worthwhile.

Late Toxicity After Adjuvant Conventional Radiation Versus Image-Guided Intensity-Modulated Radiotherapy for Cervical Cancer (PARCER): A Randomized Controlled Trial.

PURPOSE: Postoperative Adjuvant Radiation in Cervical Cancer (PARCER), a phase III randomized trial, compared late toxicity after image-guided intensity-modulated radiotherapy (IG-IMRT) with three-dimensional conformal radiation therapy (3D-CRT) in women with cervical cancer undergoing postoperative radiation. METHODS: Patients were randomly assigned to receive either IG-IMRT or 3D-CRT after stratification for the type of hysterectomy and use of concurrent chemotherapy. The primary end point was 3-year grade ≥ 2 late GI toxicity assessed using Common Toxicity Criteria for Adverse Events v 3.0 and estimated using time-to-event, intention-to-treat analysis, with a study level type I error of 0.05 and a nominal α of .047 after accounting for one interim analysis. Secondary end points included acute toxicity, health-related quality of life, and pelvic relapse-free, disease-free, and overall survival. RESULTS: Between 2011 and 2019, 300 patients were randomly assigned (IG-IMRT 151 and 3D-CRT 149). At a median follow-up of 46 (interquartile range, 20-72) months, the 3-year cumulative incidence of grade ≥ 2 late GI toxicity in the IG-IMRT and 3D-CRT arms were 21.1% versus 42.4% (hazard ratio [HR] 0.46; 95% CI, 0.29 to 0.73; P < .001). The cumulative incidence of grade ≥ 2 any late toxicity was 28.1% versus 48.9% (HR 0.50; 95% CI, 0.33 to 0.76; P < .001), respectively. Patients reported reduced diarrhea (P = .04), improved appetite (P = .008), and lesser bowel symptoms (P = .002) with IG-IMRT. However, no difference was observed in the time by treatment interaction. The 3-year pelvic relapse-free survival and disease-free survival in the IG-IMRT versus the 3D-CRT arm were 81.8% versus 84% (HR 1.17; 95% CI, 0.68 to 1.99; P = .55) and 76.9% versus 81.2% (HR 1.03; 95% CI, 0.62 to 1.71; P = .89), respectively. CONCLUSION: IG-IMRT results in reduced toxicity with no difference in disease outcomes.

Factors affecting the quality of voice in the early glottic cancer treated with radiotherapy.

AIMS: To prospectively analyze the objective voice quality before and after radiotherapy (RT) for early glottic cancer and to evaluate the role of different factors that may affect it. METHODS: Patients with T1-T2N0M0 glottic cancer underwent voice quality assessment before treatment and after radical RT. Post-RT voice quality was compared to the voice at diagnosis and the voice of healthy individuals used as controls. A comprehensive set of voice parameters were measured. The effects of age, smoking history, T stage, anterior commissure (AC) involvement, radiation dose, fractionation and volumes on pre-treatment and post-treatment voice quality were analyzed. RESULTS: The voice quality data of 50 patients were analyzed. Following treatment, there was a significant improvement in the majority of measured parameters. However, perturbation and HNR remained inferior compared to controls. A history of smoking, AC involvement and larger RT volumes resulted in poorer voice parameters following RT. There was no significant impact of age alone. T2 tumors had an inferior voice quality before treatment, but did not remain inferior following RT. Hypofractionated RT did not show any negative impact. CONCLUSIONS: There is a considerable improvement of voice quality following RT. Several factors may have specific effects on pre-treatment and post-treatment voice.

Squamous cell carcinoma of the hypopharynx: single-institution outcome analysis of a large cohort of patients treated with primary non-surgical approaches.

INTRODUCTION: Hypopharyngeal cancers have extensive submucosal spread, high risk of nodal involvement and relatively high propensity of distant metastases. Contemporary paradigms for hypopharyngeal cancers aim to maximize loco-regional control while attempting to preserve laryngo-pharyngeal form and function. AIMS: To retrospectively review outcome of large cohort of patients with hypopharyngeal cancers treated with curative intent radiotherapy with or without systemic chemotherapy in an academic tertiary referral centre. MATERIAL AND METHODS: Medical records of patients with hypopharyngeal cancers treated with primary non-surgical approaches over a 15-year period were reviewed retrospectively. Loco-regional control (LRC) and disease-free survival (DFS) were considered as outcome measures. RESULTS: Electronic search of database identified 501 patients with hypopharyngeal cancers treated with definitive radiotherapy. The median age was 55 years (range 20-87 years) and median radiotherapy dose 70 Gy (range 5.4-72 Gy). With a mean follow-up period of 22 months (median 12 months), the 3-year LRC and DFS was 47.1% and 40.9% respectively. Stage (T-stage, N-stage, overall stage grouping), and age influenced outcome significantly. The 3-year LRC for T1-T2 disease was 49.7% versus 43.1% for T3- T4 stage (p0.056). The 3-year DFS was 49.4% and 36.9% respectively (p0.014). The 3-year LRC and DFS for N0; N1; and N2-3 disease was 57.3% & 54.3%; 40.5% & 35.3%; and 33% & 27% respectively with highly significant p-values. CONCLUSION: This is an outcome analysis of the largest cohort of patients with hypopharyngeal cancers managed with primary non-surgical approaches. Stage and age remain the most important determinants of outcome.

Potential role of cancer stem cells as biomarkers and therapeutic targets in cervical cancer.

BACKGROUND: Eradicating cancer stem cells (CSCs) that are termed as the "beating heart" of various malignant tumors, including cervical cancer, holds great importance in cancer therapeutics. CSCs not only confer chemo-radio resistance but also play an important role in tumor metastasis and thereby pose a potential barrier for the cure of cervical cancer. Cervical cancer, a common malignancy among females, is associated with high morbidity and mortality rates, and the study on CSCs residing in the niche is promising. RECENT FINDINGS: Biomarker approach to screen the cervical CSCs has gained impetus since the past decade. Progress in identification and characterization of the stem cell biomarkers has led to many insights. For the diagnostic purpose, several biomarkers like viral (HPV16), stem cell markers, transcription factors (viz, SOX2, OCT 4, and c-Myc), and CSC surface markers (viz, ALDH1 and CD44) have been identified. The research so far has been directed to study the CSC stemness and demonstrates various gene expression signatures in cervical CSCs. Such studies hold a potential to improve diagnostic accuracy and predict therapeutic response and clinical outcome in patients. CONCLUSIONS: Stem cell biomarkers have been validated and their therapeutic targets are being developed as "strategies to improve therapeutic ratio in personalized medicine." This review gives a brief overview of the cervical CSC biomarkers, their current and future diagnostic, prognostic, and therapeutic potential.

Estimation of risk of radiation-induced carcinogenesis in adolescents with nasopharyngeal cancer treated using sliding window IMRT.

PURPOSE: To estimate the risk of radiation-induced carcinogenesis based on whole-body dose measurement on adolescent patients undergoing intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Ten adolescent patients with nasopharyngeal cancer were planed and treated to a dose of 70.2 Gy using sliding window IMRT. Peripheral dose (PD) was measured using thermoluminescent dosimeters kept at anterior, lateral and posterior positions of each axial plane at the level of xiphoid process, umbilicus and gonads of every patient. The associated risk of radiation-induced carcinogenesis was estimated based on the measured whole-body dose and using age- and sex-specific ICRP-60 nominal probability coefficient of 7.5% (boys) and 9.5% (girls) per Sv. RESULTS: In all patients, measured PD per monitor unit (MU) decreases almost exponentially with out-of-field distance and varies with gantry angle. Highest whole-body dose equivalent ranged from 0.5318 to 0.9867 Sv (mean=0.8141 Sv, SD=0.138) which was measured posteriorly at the level of xiphoid process. Whole-body dose was represented by the average dose at xiphoid process and all measurement positions ranged from 0.3661 to 0.8766 Sv (mean=0.658 Sv, SD=0.16) and 0.2267 to 0.5277 Sv (mean=0.3859 Sv, SD=0.09), respectively. The associated mean risk of radiation-induced carcinogenesis estimated based on different representation of mean whole-body dose was 6.57%, 5.3% and 3.11%, respectively. Higher mean risk of 7.32% was estimated among girls as compared to 6.25% for boys. CONCLUSIONS: Knowledge of risk of secondary malignancy is particularly important in adolescents and should be considered when choosing the optimal treatment technique and delivery system.

National Cancer Grid of India Consensus Guidelines on the Management of Cervical Cancer.

Standard guidelines for the management of early and locally advanced cervical cancer are available from various academic consortiums nationally and internationally. However, implementing standard-of-care treatment poses unique challenges within low- and middle-income countries, such as India, where diverse clinical care practices may exist. The National Cancer Grid, a consortium of 108 institutions in India, aims to homogenize care for patients with cervical cancer by achieving consensus on not only imaging and management, but also in addressing potential solutions to prevalent challenges that affect the homogenous implementation of standard-of-care treatment. These guidelines therefore represent a consensus statement of the National Cancer Grid gynecologic cancer expert group and will assist in homogenization of the therapeutic management of patients with cervical cancer in India.

Treatment planning comparison of electron arc therapy and photon intensity modulated radiotherapy for Askin's tumor of chest wall.

BACKGROUND AND PURPOSE: A dosimetric study to quantitatively compare radiotherapy treatment plans for Askin's tumor using Electron Arc (EA) vs. photon Intensity Modulated Radiotherapy (IMRT). MATERIALS AND METHODS: Five patients treated with EA were included in this study. Treatment plans were generated for each patient using EA and IMRT. Plans were compared using dose volume histograms (DVH) of the Planning Target Volume (PTV) and Organs at Risk (OAR). RESULTS: IMRT resulted in superior PTV coverage, and homogeneous dose distribution compared to EA. For EA, 92% of the PTV was covered to 85% of the dose compared to IMRT in which 96% was covered to 95% of the dose. V(107) that represents the hot spot within the PTV was more in IMRT compared to EA: 7.4(+/-2)% vs. 3(+/-0.5)%, respectively. With PTVs located close to the spinal cord (SC), the dose to SC was more with EA, whereas for PTVs located away from the SC, the dose to SC was more with IMRT. The cardiac dose profile was similar to that of SC. Ipsilateral lung received lower doses with IMRT while contralateral lung received higher dose with IMRT compared to EA. For non-OAR normal tissues, IMRT resulted in large volumes of low dose regions. CONCLUSIONS: IMRT resulted in superior PTV coverage and sparing of OAR compared to EA plans. Although IMRT seems to be superior to EA, one needs to keep in mind the volume of low dose regions associated with IMRT, especially while treating young children.

Clinical application of a OneDose MOSFET for skin dose measurements during internal mammary chain irradiation with high dose rate brachytherapy in carcinoma of the breast.

In our earlier study, we experimentally evaluated the characteristics of a newly designed metal oxide semiconductor field effect transistor (MOSFET) OneDose in-vivo dosimetry system for Ir-192 (380 keV) energy and the results were compared with thermoluminescent dosimeters (TLDs). We have now extended the same study to the clinical application of this MOSFET as an in-vivo dosimetry system. The MOSFET was used during high dose rate brachytherapy (HDRBT) of internal mammary chain (IMC) irradiation for a carcinoma of the breast. The aim of this study was to measure the skin dose during IMC irradiation with a MOSFET and a TLD and compare it with the calculated dose with a treatment planning system (TPS). The skin dose was measured for ten patients. All the patients' treatment was planned on a PLATO treatment planning system. TLD measurements were performed to compare the accuracy of the measured results from the MOSFET. The mean doses measured with the MOSFET and the TLD were identical (0.5392 Gy, 15.85% of the prescribed dose). The mean dose was overestimated by the TPS and was 0.5923 Gy (17.42% of the prescribed dose). The TPS overestimated the skin dose by 9% as verified by the MOSFET and TLD. The MOSFET provides adequate in-vivo dosimetry for HDRBT. Immediate readout after irradiation, small size, permanent storage of dose and ease of use make the MOSFET a viable alternative for TLDs.

Somatic Variations in Cervical Cancers in Indian Patients.

There are very few reports that describe the mutational landscape of cervical cancer, one of the leading cancers in Indian women. The aim of the present study was to investigate the somatic mutations that occur in cervical cancer. Whole exome sequencing of 10 treatment naïve tumour biopsies with matched blood samples, from a cohort of Indian patients with locally advanced disease, was performed. The data revealed missense mutations across 1282 genes, out of 1831 genes harbouring somatic mutations. These missense mutations (nonsynonymous + stop-gained) when compared with pre-existing mutations in the COSMIC database showed that 272 mutations in 250 genes were already reported although from cancers other than cervical cancer. More than 1000 novel somatic variations were obtained in matched tumour samples. Pathways / genes that are frequently mutated in various other cancers were found to be mutated in cervical cancers. A significant enrichment of somatic mutations in the MAPK pathway was observed, some of which could be potentially targetable. This is the first report of whole exome sequencing of well annotated cervical cancer samples from Indian women and helps identify trends in mutation profiles that are found in an Indian cohort of cervical cancer.

Internal target volume for post-hysterectomy vaginal recurrences of cervical cancers during image-guided radiotherapy.

OBJECTIVE: The outcome of post-surgical recurrences of cervical cancer may be improved through radiation dose escalation, which hinges on accurate identification and treatment of the target. The present study quantifies target motion during course of image-guided radiotherapy (IGRT) for vault cancers. METHODS: All patients underwent planning CT simulation after bladder-filling protocol. A daily pre-treatment megavoltage CT was performed. All translations and rotations were recorded. Post-registration displacement of gross tumour volume (GTV) and centre of mass (COM) of GTV was independently recorded by two observers for fractions one to seven. Day 1 image sets served as reference images against which the displacements of COM were measured. We calculated the displacements of common volume (CV) and encompassing volume (EV) of GTV for both the observers. RESULTS: A total of 90 image data sets of 15 patients were available for evaluation. Individual patient GTV and average GTV by both the observers were comparable. The average shifts for EV were 2.4 mm [standard deviation (SD) ±1.2] in the mediolateral, 4.2 mm (SD ±2.8) in the anteroposterior and 4.0 mm (SD ±2.1) in superoinferior directions. Similarly, the average shifts for CV were 1.9 mm (SD ±0.6) in the mediolateral, 3.7 mm (SD ±2.7) in the anteroposterior and 4.4 mm (SD ±2.7) in superoinferior directions. Using Stroom's/van Herk's formula, the minimum recommended margins would be 4.5/5.2, 8.2/9.4 and 7.3/8.3 mm, respectively, for lateral, anteroposterior and superoinferior directions. CONCLUSION: Differential directional internal margin is recommended in patients undergoing IGRT for post-surgical recurrence of cervical cancers. ADVANCES IN KNOWLEDGE: Internal organ motion of vault cancers can be accounted for by a directional margin to the gross tumour.

Uncertainties of deformable image registration for dose accumulation of high-dose regions in bladder and rectum in locally advanced cervical cancer.

PURPOSE: To compare the dose accumulation for bladder and rectum by deformable image registration (DIR) and direct addition (DA) of dose volume histogram parameters in magnetic resonance image-guided adaptive brachytherapy (IGABT). Two DIR algorithms, contour- and intensity-based, also have been analyzed. METHODS AND MATERIALS: Patients (n = 21) treated with IGABT for carcinoma cervix under the IntErnational study on MRI-guided BRachytherapy in locally Advanced CErvical cancer protocol were analyzed. Each patient underwent two HDR-BT applications, 1-week apart with two fractions of 7 Gy each delivered per application. For each application, magnetic resonance imaging, volume delineation, reconstruction, treatment planning (BT1 and BT2), and dose evaluation were carried out. BT1 and BT2 images were registered using an intensity-based DIR, followed by deformable dose accumulation (DDA), which was then compared with DA. To compare the intensity-based DIR to other DIR approaches, nine patients were further evaluated using an in-house contour-based DIR algorithm for bladder dose accumulation. RESULTS: Mean (±standard deviation; range) percentage variation between DA and DDA was found to be 2.4% (±3.3;-1.8, 11.5) and 5.2% (±5.1;-1.7, 16.5) for the rectum and bladder, respectively. The differences between the DA and DDA were found to be statistically significant for both rectum (p = 0.008) and bladder (p = 0.0003). Intensity-based DIR algorithm resulted in a larger mean deviation between DDA and DA as compared with contour-based DIR, although statistically insignificant (p = 0.32). The difference between DDA and DA was 2.4 ± 2.0% and 1.3 ± 1.2%, for intensity- and contour-based DIR, respectively. CONCLUSIONS: DA of dose volume histogram parameters provides a good estimate to the dose to the organs at risk; DIR based on image intensities may lead to systematic underestimation of dose due to implausible DIR.

Dosimetric comparison of three-dimensional conformal radiotherapy, intensity modulated radiotherapy, and helical tomotherapy for lung stereotactic body radiotherapy.

To compare the treatment plans generated with three-dimensional conformal radiation therapy (3DCRT), intensity modulated radiotherapy (IMRT), and helical tomotherapy (HT) for stereotactic body radiotherapy of lung, twenty patients with medically inoperable (early nonsmall cell lung cancer) were retrospectively reviewed for dosimetric evaluation of treatment delivery techniques (3DCRT, IMRT, and HT). A dose of 6 Gy per fraction in 8 fractions was prescribed to deliver 95% of the prescription dose to 95% volume of planning target volume (PTV). Plan quality was assessed using conformity index (CI) and homogeneity index (HI). Doses to critical organs were assessed. Mean CI with 3DCRT, IMRT, and HT was 1.19 (standard deviation [SD] 0.13), 1.18 (SD 0.11), and 1.08 (SD 0.04), respectively. Mean HI with 3DCRT, IMRT, and HT was 1.14 (SD 0.05), 1.08 (SD 0.02), and 1.07 (SD 0.04), respectively. Mean R50% values for 3DCRT, IMRT, and HT was 8.5 (SD 0.35), 7.04 (SD 0.45), and 5.43 (SD 0.29), respectively. D2cm was found superior with IMRT and HT. Significant sparing of critical organs can be achieved with highly conformal techniques (IMRT and HT) without compromising the PTV conformity and homogeneity.

Setup error analysis in helical tomotherapy based image-guided radiation therapy treatments.

The adequacy of setup margins for various sites in patients treated with helical tomotherapy was investigated. A total of 102 patients were investigated. The breakdown of the patients were as follows: Twenty-five patients each in brain, head and neck (H and N), and pelvis, while 12 patients in lung and 15 in craniospinal irradiation (CSI). Patients were immobilized on the institutional protocol. Altogether 2686 megavoltage computed tomography images were analyzed with 672, 747, 622, 333, and 312 fractions, respectively, from brain, H and N, pelvis, lung, and CSI. Overall systematic and random errors were calculated in three translational and three rotational directions. Setup margins were evaluated using van Herk formula. The calculated margins were compared with the margins in the clinical use for various directions and sites. We found that the clinical isotropic margin of 3 mm was adequate for brain patients. However, in the longitudinal direction it was found to be out of margin by 0.7 mm. In H and N, the calculated margins were well within the isotropic margin of 5 mm which is in clinical use. In pelvis, the calculated margin was within the limits, 8.3 mm versus 10 mm only in longitudinal direction, however, in vertical and lateral directions the calculated margins were out of clinical margins 11 mm versus 10 mm, and 8.7 mm versus 7.0, mm respectively. In lung, all the calculated margins were well within the margins used clinically. In CSI, the variation was found in the middle spine in the longitudinal direction. The clinical margins used in our hospital are adequate enough for sites H and N, lung, and brain, however, for CSI and pelvis the margins were found to be out of clinical margins.

Positioning high-dose radiation in multidisciplinary management of unresectable cholangiocarcinomas: review of current evidence.

Cholangiocarcinoma is a rare malignancy of the bile ducts. The current standard of care for unresectable nonmetastatic disease is doublet systemic chemotherapy, which provides a median survival of 11.7 months. Although chemoradiation is a therapeutic option that provides almost equivalent or superior survival, the lack of level I evidence presents a major hurdle in routinely recommending it within multidisciplinary clinics. This mini review presents the current evidence on the use of chemoradiation for unresectable nonmetastatic cholangiocarcinoma and rationale for positioning it within multidisciplinary management of unresectable cholangiocarcinomas.

Rapid Arc, helical tomotherapy, sliding window intensity modulated radiotherapy and three dimensional conformal radiation for localized prostate cancer: a dosimetric comparison.

OBJECTIVE: The objective of this study was to investigate the potential role of RapidArc (RA) compared with helical tomotherapy (HT), sliding window intensity modulated radiotherapy (SW IMRT) and three-dimensional conformal radiation therapy (3D CRT) for localized prostate cancer. MATERIALS AND METHODS: Prescription doses ranged from 60 Gy to planning target volume (PTV) and 66.25 Gy for clinical target volume prostate (CTV-P) over 25-30 fractions. PTV and CTV-P coverage were evaluated by conformity index (CI) and homogeneity index (HI). Organ sparing comparison was done with mean doses to rectum and bladder. RESULTS: CI 95 were 1.0 ± 0.01 (RA), 0.99 ± 0.01 (HT), 0.97 ± 0.02 (IMRT), 0.98 ± 0.02 (3D CRT) for PTV and 1.0 ± 0.00 (RA, HT, SW IMRT and 3D CRT) for CTV-P. HI was 0.11 ± 0.03 (RA), 0.16 ± 0.08 (HT), 0.12 ± 0.03 (IMRT), 0.06 ± 0.01 (3D CRT) for PTV and 0.03 ± 0.00 (RA), 0.05 ± 0.01 (HT), 0.03 ± 0.01 (SW IMRT and 3D CRT) for CTV-P. Mean dose to bladder were 23.68 ± 13.23 Gy (RA), 24.55 ± 12.51 Gy (HT), 19.82 ± 11.61 Gy (IMRT) and 23.56 ± 12.81 Gy (3D CRT), whereas mean dose to rectum was 36.85 ± 12.92 Gy (RA), 33.18 ± 11.12 Gy (HT, IMRT) and 38.67 ± 12.84 Gy (3D CRT). CONCLUSION: All studied intensity-modulated techniques yield treatment plans of significantly improved quality when compared with 3D CRT, with HT providing best organs at risk sparing and RA being the most efficient treatment option, reducing treatment time to 1.45-3.7 min and monitor unit to <400 for a 2 Gy fraction.

Inter-application variation of dose and spatial location of D(2cm(3)) volumes of OARs during MR image based cervix brachytherapy.

PURPOSE: Evaluation of Inter-application variation of doses and spatial location of D(2cm(3)) volumes of OARs during MR-image based cervix brachytherapy. MATERIALS AND METHODS: Twenty-seven patients treated with EMBRACE protocol were analyzed. Every patient had two applications, one week apart. For each application patient had undergone MR-imaging (MR-1 and MR-2), volume delineation, reconstruction, treatment planning (plan-1 and plan-2) and dose evaluation. Both the image series were then co-registered with applicator as the reference coordinate system (Eclipse planning system v8.6.14). Inter-application dose, volume and spatial location of D(2cm(3)) variation were evaluated. RESULTS: The largest inter-application systematic and random dose variations were observed for sigmoid as compared to rectum and bladder. The mean (±SD) of the relative D(2cm(3)) variations were 0.6(±15.1)%, 0.9(±13.1)% and 11.9(±37.5)% for rectum, bladder and sigmoid respectively. The overlap of D(2cm(3)) volumes was more than 50% in 16(59%), 8(30%) and 3(11%) patients for rectum, bladder and sigmoid, respectively. CONCLUSION: The 2cm(3) volumes between the applications/fractions are quite stable in topography for bladder and rectum, and hence the current practice of cumulative addition of D(2cm(3)) dose is expected to be valid for bladder and rectum. For sigmoid, significant topographical changes were seen, which need further validation in a larger patient population and in multi-centric settings.

Expression profiling of cervical cancers in Indian women at different stages to identify gene signatures during progression of the disease.

Cervical cancer is the second most common cancer among women worldwide, with developing countries accounting for >80% of the disease burden. Although in the West, active screening has been instrumental in reducing the incidence of cervical cancer, disease management is hampered due to lack of biomarkers for disease progression and defined therapeutic targets. Here we carried out gene expression profiling of 29 cervical cancer tissues from Indian women, spanning International Federation of Gynaecology and Obstetrics (FIGO) stages of the disease from early lesion (IA and IIA) to progressive stages (IIB and IIIA-B), and identified distinct gene expression signatures. Overall, metabolic pathways, pathways in cancer and signaling pathways were found to be significantly upregulated, while focal adhesion, cytokine-cytokine receptor interaction and WNT signaling were downregulated. Additionally, we identified candidate biomarkers of disease progression such as SPP1, proliferating cell nuclear antigen (PCNA), STK17A, and DUSP1 among others that were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in the samples used for microarray studies as well in an independent set of 34 additional samples. Integrative analysis of our results with other cervical cancer profiling studies could facilitate the development of multiplex diagnostic markers of cervical cancer progression.

HPV genotyping and site of viral integration in cervical cancers in Indian women.

Persistent HPV infection plays a major role in cervical cancer. This study was undertaken to identify HPV types in a cohort of Indian women with locally advanced cervical cancer as well as to determine the physical state and/or site of viral integration in the host genome. Pretreatment biopsies (n = 270) from patients were screened for HPV infection by a high throughput HPV genotyping assay based on luminex xMAP technology as well as MY09/11 PCR and SPF1/2 PCR. Overall HPV positivity was observed to be 95%, with HPV16 being most common (63%) followed by infection with HPV18. Integration status of the virus was identified using Amplification of Papillomavirus Oncogene Transcripts (APOT) assay in a subset of samples positive for HPV16 and/or HPV18 (n = 86) and with an adequate follow-up. The data was correlated with clinical outcome of the patients. Integration of the viral genome was observed in 79% of the cases and a preference for integration into the chromosomal loci 1p, 3q, 6q, 11q, 13q and 20q was seen. Clinical data revealed that the physical state of the virus (integrated or episomal) could be an important prognostic marker for cervical cancer.