Head and neck cancer is the sixth most common malignancy worldwide. Tobacco smoking and alcohol consumption are two well known behavioral risk factors associated with head and neck cancer. Recently, evidence is mounting that infection with human papilloma virus, most commonly human papilloma virus-16 is responsible for a subset of head and neck squamous cell carcinoma especially tumors of tonsillar origin. The molecular pathway used by human papilloma virus to trigger malignant transformation of tissue is different from that of other well known risk factors, i.e. smoking and alcohol, associated with squamous cell carcinoma. Apparently, these subsets of patients with human papilloma virus positive tumor are more likely to have a better prognosis than human papilloma virus negative tumor. Considering this fact, the human papilloma virus infection should be determined in all oropharyngeal cancers since it can have a major impact on the decision making process of the treatment.

The objective of this paper is to carry out a systemic review of the literature investigating issues related to bone health in survivors of breast cancer. Given the fact that only a fraction of women with breast cancer receive appropriate assessment of their bone health, it is hoped that this review will help raise awareness of bone health concerns in this patient population. Articles published in the English language addressing issues related to bone health in breast cancer were accessed using Pubmed database. Studies were searched using keywords like: "Osteoporosis", "osteopenia", "bone health", "breast cancer", "denosumab" and "bisphosphonates". Current evidence suggests that women who survive their breast cancer are at high risk for significant bone loss. Recent clinical guidelines recommend assessment of bone mineral density (BMD) in high-risk patients. Nonpharmacologic interventions including lifestyle changes, vitamin D and calcium supplements are extremely important. Bisphosphonates, in both oral and parenteral formulations, are increasingly used while new agents, like denosumab, have recently been approved. Due to the widespread use of screening mammography and early detection programs leading to breast cancer diagnosis at a much earlier stage and the recent introduction of more effective anticancer therapy, more women are surviving their breast cancer, which highlights the need for survivorship programs that address issues like bone health. Many recent professional societies are addressing these issues and updating their recommendations and guidelines.

Chemotherapy-induced cognitive changes have come under immense speculation in recent years. This mild cognitive impairment evinced in the form of short-term memory loss, and attention and concentration problems, finds itself unavoidably attached to the terms 'chemobrain' or 'chemofog'. The predicament between chemotherapy (CT) and neurotoxicity has been considerably examined and most of its attributes have been documented through neuropsychological studies. Although a sizeable portion of literature now covers this phenomenon, certain methodological reservations come in the way of its full appreciation, limited mostly by standardization issues in neuropsychological studies. The current review discusses some of these issues, with emphasis on the underlying mechanisms of progressing cognitive dysfunction in the breast cancer population, accentuating a frontosubcortical involvement and the use of competent neuropsychological batteries and structural and functional imaging techniques, to analyze the changes associated with chemotherapy. The relevance of prospective longitudinal studies with culture-centric norms has been emphasized, with the need for clinical guidelines, to assess and follow the course of neurotoxicity. Keeping track of the patient's own perceptive cognitive loss will help harmonize the decision-making process during chemotherapy.

Purpose: The aim of our retrospective analysis was to study and report the clinical outcome of patients with uterine sarcoma (US) treated at our center; and to share our experience with literature. Materials and Methods: We retrieved the information regarding the patient's demography, clinico-pathological details, treatment given, survival, and complications of all the US patients treated at our center between the years 2000-2008. The three-year overall survival (OS) was determined with respect to various prognostic factors like age, stage of disease, histopathological type, adjuvant RT etc. Results: A total of 50 case records were retrieved for this retrospective analysis. Age ranged from 24 to 75 years with a median of 50 years. Carcinosarcoma was the commonest histopathological type (23/50 patients). FIGO stage distribution was: stage I, 27; stage II, 7; stage III, 12; stage IV, 2; and unknown stage, two patients. Forty-eight patients underwent surgery; 31 received postoperative radiation therapy (PORT) and 16 received chemotherapy therapy. Median follow-up period was 34 months (range 2-69 months). The three-year OS for the entire group of patients was 42%. Stage of the disease, histopathological type, and use of PORT were found significant prognostic factors for survival. Conclusion: Although limited by small sample size and retrospective nature, ours is the only study on US being reported from India. Our results have demonstrated FIGO stage of the disease, histopathology and use of PORT to be the significant prognostic factor for survival. Use of chemotherapy in future trials is warranted.

Background: Quality of Life (QOL) measures have now become a vital part of health outcome appraisal and an effective way of capturing the personal and social context of patients. Aim: To assess the QOL of cancer patients by using a validated questionnaire. Settings and Design: A prospective study in the medical oncology clinic of a tertiary care hospital of South India. Materials and Methods: Patients receiving chemotherapy for different types of cancer were subjected to a validated questionnaire and their responses to the factors of the questionnaire were scored and analyzed. A Chi-square test was performed to assess the effect of age and type of cancer on the QOL of patients. Pearson's correlation was done to assess the factors that had greater influence on the QOL. Results: A total of 32 (15 males; 17 females) patients were included and majority were in the age range of 61-80 years. Eleven types of cancer were identified. About 56% of the patients were assessed to have average QOL and 28% had below average QOL, 9% had above average, and 2 (6.25%) had significantly high QOL. The overall mean QOL score of the study population was 122.38 ± 13.86. Factors 1 (psychological well-being), 2 (self-adequacy), 3 (physical wellbeing), 4 (confidence in self-ability), 6 (pain), 7 (mobility), and 8 (optimism and belief) had significant influence on the QOL, while factors 5 (external support), 9 (interpersonal relationship), and 10 (self-sufficiency and independence) did not have a significant effect on QOL. Age (P=0.396) and type of cancer (P=0.371) did not have a significant effect on the QOL. Conclusion: The study showed that 80% of the total study population reported to have average and below average QOL, suggesting that an increasing importance is given to the incorporation of Quality of Life as an outcome, in addition to other clinical endpoints.

Background: Multicystic ameloblastoma is a benign odontogenic tumor that exhibits a more aggressive behavior than keratocystic odontogenic tumor (KCOT) and follicular cyst. Aim: The purpose of the study was to evaluate the proliferation index nuclear organizer regions (NORs) and their distribution among the four odontogenic lesions with known different clinical invasive behavior. Study and Design: In a descriptive-analytical cross-sectional study, 60 paraffin blocks of odontogenic lesions were prepared for silver nitrate staining. Materials and Methods: For the quantitative analysis, 100 cells were counted at ×100 and the mean value was calculated. The morphometric analysis of NORs showed that they can be distributed into normal (round to oval-shaped) and abnormal (large, bean-shaped and cluster-shaped) groups. One-way analysis of variance (ANOVA) and multiple comparison with Tukey test were used for the statistical analysis of the results. Results: The argyrophilic NOR (AgNOR) numbers in multicystic ameloblastoma, unicystic ameloblastoma, KCOT, and follicular cyst were 7.4 ± 2.7, 6.1 ± 2.56, 4.7 ± 1.84, and 2.82 ± 1.052, respectively. The difference between ameloblastoma (unicystic and multicystic types) and either_KCOT, or follicular cyst was statistically significant (P<0.001) and, (P=0.001), respectively. In follicular cysts, normal AgNOR dots were not detected outside the nuclei. NOR histological patterns of KCOT were large, bean shaped and rarely cluster shaped and it was cluster-shaped in multicystic and unicystic ameloblastoma. Conclusion: The current study suggests that determination of clinical behavior of ameloblastoma in comparison with KCOT and follicular cyst in silver nitrate staining is related to higher proliferation activity and different NORs' distribution pattern. However, further clinical follow-up studies must be performed to prove this.

Aim: The present study was aimed to analyze the chromosomal changes and also to work out the association of some of the non-cytogenetic factors in the confirmed cases of cervical carcinoma. Materials and Methods: Slides for the chromosome study were prepared from the tumor growths of 78 patients as the diagnosed cases of cervical carcinoma. The slides so prepared were then subjected to G-banding to rule the involvement of different chromosomes in the progression of cervical cancer. Non-cytogenetic factors that are considered to be the risk factors for CaCx were also taken up during the present study to study the etiology of cervical cancer. Results: Both the numerical and the structural chromosomal changes have been recorded in a majority of these growths. In most of the cases, numerical chromosomal changes (95%) outnumbered the structural aberrations. Discussion: Aneuploidy was the most common numerical chromosomal aberration recorded in the majority of the tumor growths. Structural aberrations included translocations and deletions. Non-cytogenetic factors like multiparity, early marriage, poor genital hygiene and rural background were highly prevalent in the present study.

Purpose: This study was designed to evaluate inter and intraobserver concordance in gross tumor volume (GTV) delineation on megavoltage CT (MVCT) images in patients with postoperative vault recurrences. Materials and Methods: Three observers delineated GTV on MVCT and CECT and two observers recontoured on MVCT images. Tumor volumes were calculated and correlated using Spearman correlation. The standard deviation of centre of mass was averaged on per patient basis. The ratio of common volume and encompassing volume was used to determine intra and interobserver spatial concordance. Lack of difference in spatial concordance ratio between MVCT and CECT images was used as an index of usability of MVCT images. Results: Thirty six datasets were available for seven patients. High intraobserver GTV correlation was recorded for observer 1 and 2 (r = 0.93 and r = 0.98; P=0.03 and 0.0001). The average intraobserver spatial concordance ratio was 0.57 and 0.62 respectively. The mean GTV of observers 1, 2 and 3 were 31.6 (18.7-52.2); 28.2 (16.7-51.8) and 46.3 cc (29.1-90.5) respectively. Average standard deviation of centre of mass of all observers was less than 5 mm in either direction. Largest interobserver discordance was observed in anterior, inferior and lateral direction. The interobserver spatial concordance of GTV on MVCT and CECT images was 0.34 and 0.36 (P=0.24) respectively. Conclusion: Moderate to good inter and intraobserver GTV correlation was observed on MVCT images, however, was associated with low interobserver spatial concordance on both MVCT and CECT images. Strategies to improve contouring reproducibility on MVCT and KVCT images are desirable.

Background: Late rectal and sigmoid toxicities seen in cervical cancer patients are attributed to brachytherapy despite rectal doses within tolerance limits. The purpose of this study was to identify additional dosimetric points which may better forecast rectal complications. Materials and Methods: Fifteen high dose rate intracavitary brachytherapy (ICA-HDR) applications with conventional X-ray and computed tomography (CT) based planning were studied. In addition to International Commission on Radiation Units and Measurement (ICRU) rectal and bladder points, proximal and distal rectal and sigmoid points were digitized on CT scans and dose volume histograms' (DVHs') parameters were computed and correlated. Results: The mean ICRU, additional distal, proximal and sigmoid point doses were 486 ± 152 cGy, 527 ± 156 cGy, 401 ± 149 cGy and 838 ± 254 cGy, respectively, for a prescription of 700 cGy to point A. The mean sigmoid point dose was significantly higher than the ICRU rectal point doses (P=0.001). The high-dose sigmoid points were situated at a mean -8 mm (range -22.95 to 10.43 mm) lateral, 10 mm posterior (range -15.87 to 27.82 mm) and 31 mm (range 8.08-62.91 mm) cranial to the intracavitary applicator flange of central tandem. Conclusions: Our dosimetric study suggests that sigmoid points and 0.1 cm ³ receive significantly higher doses than rectal points during ICA-HDR in carcinoma of the uterine cervix. No definite conclusion on reproducible spatial distribution on orthogonal X-rays could be achieved. To document and reduce sigmoid doses, some form of 3D image-based planning is necessary.

Background: Stereotactic body radiation therapy is an advanced technique, which delivers ablative doses to lung lesions. Target verification is done either by orthogonal x-rays or cone beam CT. This study was undertaken to compare these two verification methods. Aim: To evaluate the efficacy of ExacTrac and Cone Beam Computed Tomography (CBCT) for target repositioning while delivering Stereotactic Body Radiation Therapy (SBRT) for lung lesions and derive the population-based margin. Materials and Methods: All patients who had undergone SBRT for lung lesions from February to September 2009 were involved. Patients were immobilized using the BodyFix double vacuum immobilization system, indexed to the computed tomography (CT) simulator and treatment machine. Four-dimensional (3-D) scan was done to generate internal target volume (ITV) and a free breathing CT scan for planning was done on the BrainLab iPlan 4.1 software. During treatment, patient's position was verified using ExacTrac and CBCT. The resulting vertical, lateral, and longitudinal shifts were noted. The random and systematic error were calculated and the margin recipe derived using the Van Herk formula. Results: Sixteen patients had undergone SBRT for lung tumors from February to September 2009. Data from eight patients who had undergone 34 sessions of SBRT was analyzed. The systematic error for lateral, longitudinal, and vertical shifts for ExacTrac and CBCT were 3.68, 4.27, 3.5 mm and 0.53, 0.38, 0.70 mm, respectively. The random error were 1.10, 1.51, 1.96 mm and 0.32, 0.81, 0.59 mm. The lateral, longitudinal and vertical Van Herk margin recipe for ExacTrac were 9.98, 11.72, 10.18 mm, respectively, and for CBCT was 2.17, 1.53,1.55 mm. Conclusions: The systematic and random errors for CBCT were significantly lesser as compared to the errors with Exactrac.

Aim: The aim was to obtain inhomogenity correction factors (ICFs) for lung tissue inhomogenity for a Co-60 teletherapy beam using Monte Carlo simulation and to compare them with factors obtained from a commercially available treatment planning system. Materials and Methods: The Monte Carlo simulation code of EGSnrc is used for the depth dose calculations. Two clinical like situations were simulated-dose calculation point beyond the lung tissue volume and dose calculation point within the lung tissue volume. The variation of ICF with lung thicknesses and positions was studied. ICF values were obtained for the similar situations from a commercially available treatment planning system, Theraplan Plus. Results: Percentage depth dose data obtained from Monte Carlo simulation is well matching with the published measurement data. ICFs for lung tissue inhomogenity calculated using the Monte Carlo code are in good agreement with Theraplan Plus TPS values for small inhomogenity thicknesses. Conclusion: These results can be used for the verification of TPS calculation or manual treatment time calculation.

Background: Efficacy of photodynamic therapy can be enhanced by improving uptake, localization, and sub-cellular localization of sensitizers at the sensitive targets. Materials and Methods: Uptake, localization, and photodynamic effects of hematoporphyrin derivative (HpD, Photosan-3; PS-3) and disulfonated aluminum phthalocyanine (AlPcS ₂ ) were studied either encapsulated in liposomes or conjugated to a monoclonal antibody to carcinoembryonic antigen (anti-CEA) in a brain glioma cell line, BMG-1. Results: Although the total uptake with encapsulated or conjugated sensitizers was less than the free sensitizers, photodynamic efficiency was higher due to the localization of the sensitizer at the sensitive targets. Biodistribution of intravenously administered technetium ( ^99m Tc)-labeled PS-3 analyzed by gamma camera imaging showed maximum accumulation in the liver followed by tumor. Tumor/muscle (T/N) ratio of free PS-3 was higher compared to encapsulated or conjugated PS-3 but the accumulation of PS-3 significantly reduced in brain and cutaneous tissue following modulated delivery. Pharmacokinetics suggested faster accumulation of encapsulated and conjugated PS-3 in the tumor. Conclusion: Localization of sensitizers at sensitive targets and reduced accumulation in normal tissues with liposome encapsulation and antibody conjugation suggest that these two delivery systems can potentially enhance the efficacy of photodynamic treatment.

Context: The most important problem in the case of thyroid nodules is the lack of suitable criteria for detecting malignant thyroid tumors from other nodules in the early stage. Variable expressions level of survivin, an inhibitory protein in apoptotic pathway, and its splice variants in malignant carcinoma versus well-differentiated normal tissues candidate them as reliable biomarkers in cancers. Aim: To semi-quantitative detection of survivin and its splice variant, survivin-deltaEx3, in thyroid nodules. Setting and Design: We evaluated the expression level of mentioned biomarkers in thyroid nodules including carcinoma. Materials and Methods: Samples were collected from 61 thyroid nodules including malignant, adenoma, non-tumoral (goiter and thyroidities) as well as non-neoplastic normal tissues. Transcriptional levels were measured using semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and the results were normalized to b2microglubin (b2m) gene. Statistical Analysis Used: Independent sample t-test was used to assess the significant variation of expression between different groups. Result: Our data for a first time revealed that survivin-deltaEx3 is significantly up-regulated from normal to malignant thyroid carcinoma tissues (approximately ten fold). Conclusion: High expression level of survivin and survivin-deltaEx3 in malignant papillary thyroid carcinoma suggested survivin gene expression and its splice variant, survivin-deltaEx3, can be potential new markers in diagnosis of human papillary thyroid carcinoma.

Purpose: The role of invasion as a prognostic factor in high-grade gliomas (HGG) remains controversial. An apparent increase in invasiveness following anti-angiogenic therapy makes this question clinically relevant. The goal of this study is to assess survival differences in patients with newly diagnosed HGG who present with diffuse invasive disease compared to those who did not, but went on to develop diffuse invasive disease following bevacizumab therapy. Materials and Methods: Twenty-three patients presented as newly diagnosed diffuse invasive HGG. All patients underwent surgical resection with radiation therapy and temozolomide for one year. Progression-free survival (PFS) and overall survival (OS) were compared to a control of 58 patients with focal high-grade glioma who received similar therapy, but that included bevacizumab at 10 mg/kg given every two weeks. Results: The patient characteristics were similar in each group. The median PFS and OS for invasive HGG patients were 6 and 13 months and for the focal HGG patients, 11 and 24 months, respectively (P=0.092 and P=0.071). In the subgroup of invasive HGG that showed significant angiogenesis, the median PFS and OS were 3 and 9 months, respectively. 56% of the focal HGG patients recurred as diffuse invasive relapse. For patients with focal HGG who recurred as invasive disease, the median PFS and OS were 9 and 21 months respectively. Conclusions: Presence of diffuse invasive disease not accompanied by angiogenesis either prior to therapy or subsequent to anti-angiogenic therapy does not seem to have prognostic significance. However, invasion accompanied by angiogenesis in newly diagnosed HGG may confer a poor prognosis.