Rural-urban disparity in cancer burden and care: findings from an Indian cancer registry.

BACKGROUND: Cancer incidence and mortality vary across the globe, with nearly two-thirds of cancer-related deaths occurring in low- and middle-income countries. The rural-urban disparity in socio-demographic, behavioural, and lifestyle-related factors, as well as in access to cancer care, is one of the contributing factors. Population-based cancer registries serve as a measure for understanding the burden of cancer. We aimed to evaluate the rural-urban disparity in cancer burden and care of patients registered by an Indian population-based cancer registry. METHODS: This study collected data from Varanasi, Uttar Pradesh, India, between 2017 and 2019. Sex and site-specific age-standardised rates for incidence and mortality per 100,000 population were calculated. Rural-urban disparities in cancer incidence and mortality were estimated through rate differences and standardised rate ratios (with 95% confidence intervals). Univariable and multivariable regressions were applied to determine any significant differences in socio-demographic and cancer-related variables according to place of residence (rural/urban). Crude and adjusted odds ratios with 95% confidence intervals were calculated. RESULTS: 6721 cancer patients were registered during the study duration. Urban patients were older and had better literacy and socioeconomic levels, while rural patients had higher odds of having unskilled or semi-skilled professions. Diagnostic and clinical confirmation for cancer was significantly higher in urban patients, while verbal autopsy-based confirmation was higher in rural patients. Rural patients were more likely to receive palliative or alternative systems of medicine, and urban patients had higher chances of treatment completion. Significantly higher incidence and mortality were observed for oral cancer among urban men and for cervical cancer among rural women. Despite the higher incidence of breast cancer in urban women, significantly higher mortality was observed in rural women. CONCLUSIONS: Low- and middle-income countries are facing dual challenges for cancer control and prevention. Their urban populations experience unhealthy lifestyles, while their rural populations lack healthcare accessibility. The distinctness in cancer burden and pattern calls for a re-evaluation of cancer control strategies that are tailor-made with an understanding of urban-rural disparities. Context-specific interventional programmes targeting risk-factor modifications, cancer awareness, early detection, and accessibility to diagnosis and care are essential.

Microbiome and Abdominopelvic Radiotherapy Related Chronic Enteritis: A Microbiome-based Mechanistic Role of Probiotics and Antibiotics.

Chronic diarrhea and abdominal pain after radiotherapy continue to be a problem in cancer survivors. Gut microbiomes are essential for preventing intestinal inflammation, maintaining intestinal integrity, maintaining enterohepatic circulation, regulating bile acid metabolism, and absorption of nutrients, including fat-soluble vitamins. Gut microbiome dysbiosis is expected to cause inflammation, bile acid malabsorption, malnutrition, and associated symptoms. Postradiotherapy, Firmicutes and Bacteroidetes phylum are significantly decreased while Fusobacteria and other unclassified bacteria are increased. Available evidence suggests harmful bacteria Veillonella, Erysipelotrichaceae, and Ruminococcus are sensitive to Metronidazole or Ciprofloxacin. Beneficial bacteria lactobacillus and Bifidobacterium are relatively resistant to metronidazole. We hypothesize and provide an evidence-based review that short-course targeted antibiotics followed by specific probiotics may lead to alleviation of radiation enteritis.

Is FAST FORWARD the Way Forward in Radiotherapy for Locally Advanced Breast Cancer - Learnings From the COVID Pandemic.

INTRODUCTION: Low middle-income countries (LMICs), including India, have paucity of external beam radiotherapy (RT) machines leading to prolonged wait times for RT. Delay in delivery of RT has been shown to adversely affect outcomes in locally advanced breast cancer (LABC). With the availability of results of multiple randomized controlled trials, hypofractionated RT delivered over 3 to 4 weeks became the standard of care in breast cancer RT. METHODS: We conducted a retrospective audit of 172 LABC patients treated with ultrahypofractionated adjuvant RT (radiotherapy completed in 1 week) during the COVID pandemic. Log rank and Cox-regression model used for univariate and multi-variate analyses. RESULTS: No patient developed grade 3 esophagitis. Grade 2 esophagitis requiring short term narcotic analgesics was seen in 12 (6.9%) patients. Grade 2 or higher toxicity peaked between 2 and 3 weeks after RT. The estimated 2 and 3- year recurrence free survival (RFS) for the cohort is 87.1 % and 81.4 %, respectively. The estimated 2 and 3-year overall survival for the cohort is 95% and 91.3%. On multivariate analysis, presence of extra-nodal extension was found to be an independent factor associated with worse RFS (P = .028). CONCLUSIONS: FAST FORWARD protocol RT in LABC appears well tolerated.

Community cancer screening at primary care level in Northern India: determinants and policy implications for cancer prevention.

OBJECTIVE: Despite the established cancer screening programme for oral, breast and cervical cancer by the Government of India, the screening coverage remains inadequate. This study aimed to describe the determinants for oral, breast and cervical cancer prevention in a rural community at the primary care level of Northern India and its policy implications. DESIGN: This was a camp-based project conducted for 1 year, using oral visual examination, clinical breast examination and visual inspection of cervix by application of 5% acetic acid according to primary healthcare operational guidelines. During the project, screen-positive participants were followed through reverse navigation. Information about socio-demographic profile, clinical and behavioural history and screening were collected. Predictors for screen-positivity and follow-up compliance were identified through multivariable analysis. SETTINGS: Based on the aim of project, one of the remotely located and low socioeconomic rural blocks, having 148 villages (estimated population of 254 285) in Varanasi district, India was selected as the service site. There is an established healthcare delivery and referral system as per the National Health Mission of Government of India. Oral, breast, gallbladder and cervical cancers are the leading cancers in the district. PARTICIPANTS: We invited all men and women aged 30-65 years residing in the selected block for the last 6 months for the screening camps. Unmarried women, women with active vaginal bleeding, those currently pregnant and those who have undergone hysterectomy were excluded from cervical cancer screening. RESULTS: A total of 14 338 participants were screened through 190 camps and the majority (61.9%) were women. Hindu religion, tobacco use, intention to quit tobacco and presence of symptoms were significantly associated with screen-positivity. Nearly one-third (220; 30.1%) of the screened-positives complied with follow-up. Young age and illiteracy were significantly associated with lower compliance. CONCLUSION: Poor follow-up compliance, despite the availability of tertiary cancer care, patient navigation, free transportation and diagnostic services, calls for research to explore the role of contextual factors and develop pragmatic interventions to justify 'close the care gap'. Community cancer screening needs strengthening through cancer awareness, establishing referral system and integration with the National Tobacco Control and Cancer Registry Programmes.

Role of verbal autopsy in cancer registration: A mixed-methods study from the population-based cancer registry of Northern India.

OBJECTIVES: To describe utilisation of verbal autopsy as one of the data collection approaches in cancer registration in an Indian setting. We aimed to estimate the proportion and epidemiological characteristics of malignancies identified by the Varanasi population-based cancer registry (PBCR) using verbal autopsy between 2017 and 2019 and to develop a thematic network for implementing verbal autopsy. METHODS: This was a cross-sectional mixed-methods study. Quantitative methods were applied to analyse information from PBCR proforma of the verbal autopsy-confirmed cancers; qualitative methods were applied to evaluate verbal autopsy conducted by field staff from key informants. In-depth interviews of field staff for the challenges and potential solutions during verbal autopsy were assessed. RESULTS: Of 6466 registered cancers, 1103 (17.1%) were verbal autopsy-confirmed cancers, which had no other source of information. The majority of verbal autopsy cases were from vulnerable populations who were aged >50 years (721, 65.4%), female (607, 55.1%), from rural backgrounds (853, 77.3%), illiterate or just able to read and write (636, 57.7%), and from lower and middle-income groups (823, 74.6%). Verbal autopsy helped provide information about symptoms and site of disease, diagnostic and treatment details, and disease status. Major challenges during verbal autopsy described by field staff were incomplete cancer treatment, destruction of medical records and non-cooperation by the community and lack of support from the local workforce as cancer is not notifiable. CONCLUSION: Verbal autopsy helped identify cancers that would have been missed during active case finding from available resources. The majority of verbal autopsy-confirmed patients belonged to vulnerable populations. Non-cooperation from community and local health systems was major challenge during verbal autopsy. Developing robust cancer awareness, patient navigation, and social support programmes will strengthen verbal autopsy. Integration of standardised and reproducible methods of verbal autopsy in cancer registry and digitalization of health information, especially in limited-resource settings with weak vital registration, will facilitate completeness in cancer registration.

Brachytherapy training in India: Results from the GEC-ESTRO-India survey.

INTRODUCTION: Brachytherapy (BT) is integral in treatment of gynecological malignancies and is also an option for many other cancers. Data on training and proficiency levels of early career oncologists is limited. Like other continents a survey was conducted for early career oncologists in India. METHODS AND MATERIALS: An online survey was conducted from November 2019 to February 2020, through Association of Radiation Oncologists of India (AROI) for early career radiation oncologists expected to be within 6 years of training. The survey used a 22 item questionnaire that was also used for European survey. Responses to individual statements were recorded on a 1-5 Likert-type scale. Descriptive statistics were used to describe proportions. RESULTS: One-hundred twenty-four (17%) of 700 recipients responded to the survey. Majority of the respondents (88%) stated that being able to perform BT at the end of their training was important. Two-thirds of the respondents (81/124) had performed >10 intracavitary procedure and 22.5% had performed >10 intracavitary-interstitial implants. Many respondents had not performed nongynecological procedure- breast (64%), prostate(82%), gastro-intestinal (47%). Respondents predicted that in next 10 years, the role of BT is likely to increase. Lack of dedicated curriculum and training was perceived as the greatest barriers to achieving independence in BT (58%). Respondents suggested that BT training should be prioritized during conferences (73%) and online teaching modules (56%), along with development of BT skills labs (65%). CONCLUSION: This survey identified a lack of proficiency in gynecological intracavitary-interstitial brachytherapy and non-gynecological brachytherapy, despite BT training being regarded as highly important. Dedicated programs, including standardized curriculum and assessment need to be developed for training early- career radiation oncologists in BT.

Cancer pattern in Varanasi district from Uttar Pradesh state of India, a foundation for cancer control based on the first report of the population-based cancer registry.

Background: The cancer registry provides reliable data from the population. In this article, we provide cancer burden and its patterns from the Varanasi district. Methods: The method adopted by the Varanasi cancer registry is community interaction along with regular visits to more than 60 sources to collect data on cancer patients. The cancer registry was established by the Tata Memorial Centre, Mumbai, in 2017 covering 4 million population (57% rural and 43% urban population). Results: The registry has recorded 1,907 incidence cases (1,058 male and 849 female). The age-adjusted incidence rate per 100,000 population in male and female of Varanasi district is 59.2 and 52.1, respectively. One in 15 male and one in 17 female are at risk of developing the disease. Mouth and tongue cancers are the predominant cancers in male, whereas breast, cervix uteri, and gallbladder are the leading cancer sites among the female. In female, cervix uteri cancer is significantly higher (double) in rural areas when compared with urban areas (rate ratio [RR] 0.5, 95% confidence interval [CI; 0.36, 0.72]), whereas in male, mouth cancer is higher in urban areas when compared with rural areas (RR 1.4, 95% CI [1.11, 1.72]). More than 50% of cancer cases in male are due to tobacco consumption. There may be underreporting of the cases. Conclusion: The results of the registry warrant policies and activities related to early detection services for the mouth, cervix uteri, and breast cancers. The Varanasi cancer registry is the foundation for cancer control and will play an important role in the evaluation of the interventions.

Evaluation of Medical Certification of Cause of Death in Tertiary Cancer Hospitals in Northern India.

BACKGROUND: Medical certification of cause of death (MCCD) provides valuable data regarding disease burden in a community and for formulating health policy. Inaccurate MCCDs can significantly impair the precision of national health information. OBJECTIVE: To evaluate the accuracy of cause of death certificates prepared at two tertiary cancer care hospitals in Northern India during the study period (May 2018 to December 2020). METHOD: A retrospective observational study at two tertiary cancer care hospitals in Varanasi, India, over a period of two and a half years. Medical records and cause of death certificates of all decedents were examined. Demographic characteristics, administrative details and cause of death data were collected using the WHO recommended death certificates. Accuracy of death certification was validated by electronic medical records and errors were graded. RESULTS: A total of 778 deaths occurred in the two centres during the study period. Of these, only 30 (3.9%) certificates were error-free; 591 (75.9%) certificates had an inappropriate immediate cause of death; 231 (29.7%) certificates had incorrectly labelled modes of death as the immediate cause of death; and 585 (75.2%) certificates had an incorrect underlying cause of death. The majority of certificates were prepared by junior doctors and were significantly associated with higher certification errors. CONCLUSION: A high rate of errors was identified in death certification at the cancer care hospitals during the study period. Inaccurate MCCDs related to cancers can potentially influence cancer statistics and thereby affect policy making for cancer control. IMPLICATIONS: This study has identified the pressing need for appropriate interventions to improve quality of certification through training of doctors.

A study for evaluating clinical relevance of circulating cell-free DNA in cervical cancer.

Introduction: Recent techniques available for the detection of cervical cancer (CC) are highly invasive and costly, which makes it a rate-limiting step toward early diagnosis of this fatal disease. Evaluation of circulating cell-free DNA (ccfDNA) through liquid biopsy is a minimally invasive and cost-effective method that may serve as a unique tumor marker for early detection, treatment monitoring, the status of residual disease, and distant tumor metastasis in CC patients. Materials and Methods: In this study, initially, ccfDNA was measured in serum samples from 11 histopathologically proven cervix carcinoma patients and 8 controls. On successful screening, it was further extended to 2 more patients with a series of serum samples extracted at 3 different phases of the concurrent chemoradiotherapy (i.e., before, during, and after 6 months of follow-up). Results: Agarose gel electrophoresis profile for ccfDNA of CC patients showed that of 11 patients, 4 patients had a comparatively higher tumor burden (ccfDNA) than the other 7 patients. Notably, during concurrent chemoradiotherapy, ccfDNA load disappeared and, after 6 months of follow-up, appeared back due to distant metastasis. Conclusion: Hence, we propose that this method could be an affordable and reliable way to diagnose/screen CC.

Lymphocyte sparing normal tissue effects in the clinic (LymphoTEC): A systematic review of dose constraint considerations to mitigate radiation-related lymphopenia in the era of immunotherapy.

BACKGROUND: Radiation-related lymphopenia has been associated with suboptimal tumor control rates leading to inferior survival outcomes. To date, no standardized dose constraints are available to limit radiation dose to resident and circulating lymphocyte populations. We undertook this systemic review of the literature to provide a synopsis of the dosimetric predictors of radiation-related lymphopenia in solid malignancies. METHODOLOGY: A systematic literature review of PubMed (National Institutes of Health), Cochrane Central (Cochrane collaboration), and Google Scholar was conducted with the following keywords: "radiation", "lymphopenia", "cancer", "dosimetric predictors" with an inclusion deadline of May 31, 2022. Studies that met prespecified inclusion criteria were designated either Good, Fair, or Poor Quality based on the Newcastle-Ottawa quality assessment. The dosimetric parameters derived from Good Quality studies were tabulated as LymphoTEC dose constraints. Dosimetric parameters derived from Fair and Poor-quality studies were grouped as optional. RESULTS: An initial systematic search of the literature yielded 1,632 articles. After screening, a total of 48 studies met inclusion criteria and were divided into the following categories: central nervous system (CNS, 6), thoracic (11), gastrointestinal (26), gynecologic (2), head and neck, breast, and genitourinary (one each) cancers. Lung mean dose, heart mean dose, brain V25, spleen mean dose, estimated dose to immune cells, and bone marrow V10 were among the strongest predictors for severe lymphopenia related to radiotherapy. CONCLUSION: Optimizing the delivery of radiation therapy to limit dose to lymphocyte-rich structures may curb the negative oncologic impact of lymphocyte depletion. The dose constraints described herein may be considered for prospective validation and future use in clinical trials to limit risk of radiation-related lymphopenia and possibly improve cancer-associated outcomes.

A mathematical model to predict the different isodose volumes using TRAK value in HDR intracavitary brachytherapy for revised Manchester and ICRU-89 based Point A plans using computer tomography images.

Purpose: To find out the simple relationship between Total Reference Air Kerma (TRAK) and various isodose volumes. Calculated isodose volumes were compared with experimental data for revised Manchester and International Commission on Radiation Units and measurements (ICRU)-89 Point A-based treatment plans. The accuracy of the formula was compared with the results of other relationships available in the literature. Materials and Methods: Dosimetric data from 62 intracavitary brachytherapy (ICBT) treatment plans of 31 patients with cervical cancer were studied. Each patient had treatment plans normalized to revised Manchester and ICRU-89 Points A (Aflange and Aicru89). For each treatment plan, TRAK values, V350, V700, V1050, and V1400 were obtained. The modeling curve was plotted between Isodose volume (Vd) and the ratio of d/TRAK obtained from Aflange plans to get a mathematical relation. The results of this formula were compared with the experimental data and outcomes of other formulas available in the literature. A paired-sample t-test was performed to assess the statistical significance. Results: In the case of revised Manchester-based Aflange normalization plans, the mean isodose volume of V350, V700, V1050, and V1400 were 285.98 ± 32.3 cm3, 101.96 ± 10.63 cm3, 52.71 ± 4.72 cm3, and 31.44 ± 2.33 cm3 respectively. Likewise, for ICRU-89 based Aicru89 normalization plans, the mean isodose volumes of V350, V700, V1050, and V1400 were 304.11 ± 26.17 cm3, 108.88 ± 8.29 cm3, 56.62 ± 3.69 cm3 and 34 ± 2.23 cm3 respectively. The mean difference was significant. The Mathematical relationship developed was [INLINE:1]. No correlation was found between TRAK and D0.1cm3,D2cm3 for organs at risk. Conclusions: The developed formula calculated isodose volumes within the accuracy of ± 3% in ICBT plans.

A Cross Sectional Assessment of the Profile of Risk Factors of Non-Communicable Diseases Among Health Care Staff of a Tertiary Cancer Hospital.

Background: Non-communicable disease (NCD) is the leading cause of death, accounting for 70% of total death globally, and posing a major public health challenge. In India, nearly 5.8 million people (WHO report, 2015) die from NCDs every year. The basic element of NCD prevention is the identification of the associated risk factors and risk modification. The objective of the current study was conducted to assess the prevalence of risk factors for NCDs among healthcare staff of the two units of a Tertiary Cancer Hospital in Varanasi, India, using WHO STEPS approach. Methods: This cross sectional study was conducted among 528 participants who were willing to participate in the study, from among 967 healthcare staffs of the two units of the Tertiary Cancer Hospital. The participants were interviewed and the anthropometric and biochemical parameters were measured. Results: The prevalence of risk factors, associated with NCD, tobacco use, alcohol use, extra salt in diet, less than 5 servings of fruits/vegetables, physical inactivity and self-perceived high stress score was found in 34 (6.43%), 90 (17.04%), 461 (87.3%), 412 (78.03%), 409 (77.4%) and 159 (30.11%) respondents, respectively. Multiple logistic regression revealed that Diabetes was significantly associated with male sex, high BMI and physical inactivity. Hypertension was found significantly associated with male sex, increasing age, tobacco and or alcohol consumption, high BMI and high stress. Dyslipidemia was also found significantly associated with high BMI, male sex, physical inactivity and high stress levels. Conclusion: A high prevalence of risk factors for NCDs was found among the healthcare staff and it is the need of the hour to take preventive measures to reduce the prevailing burden of NCD.

VEGFa/VEGFR2 autocrine and paracrine signaling promotes cervical carcinogenesis via ß-catenin and snail.

VEGF secretion into the tumor microenvironment by cancer cells regulates several oncogenic signaling pathways and cancer-regulated angiogenesis. VEGFR receptors are exclusively present on endothelial cells to maintain their biological homeostasis. The acquisition of unique VEGFR2 receptor and VEGFa in cervical cancer (CC) cells reflects VEGFa/VEGFR2 autocrine machinery. Given the critical role of VEGFR2 in endothelial cell proliferation, migration, and angiogenesis, we explored its function in CC epithelial-mesenchymal transition (EMT) and stemness. Here we report that VEGFR2 regulates cancer-induced angiogenesis and EMT-linked stemness in CC cells via AKT/GSK3ß/ß-catenin and Snail pathway. Receptor tyrosine kinase inhibitor (RTKi) of VEGFR, Pazopanib (PAZ), shows potential anti-VEGFR2 activity and inhibits VEGFa induced metastatic events such as migration, invasion, and anoikis resistance in CC cells. Similarly, PAZ also attenuates cancer-regulated angiogenesis by inhibiting VE-cadherin internalization in endothelial cells followed by inhibition of endothelial cell migration. Selective depletion of VEGFR2 ligand VEGFa in CC cells also attenuates EMT, metastatic events, and inhibition of cancer-induced angiogenesis. In addition, blocking of VEGFR2 signaling in CC cells via PAZ or shRNA alters the formation of cervical tumorspheres (TS) and their successive generation. Collectively, inhibition of functional VEGFa/VEGFR2 autocrine and paracrine axis ceases the cancer-promoting events in cervical cancer cells. Based on the finding in this study, this oncogenic pathways could be used as a potential therapeutic target in a clinical setting with conventional radio-chemotherapy to achieve synergistic killing of CC cells.

Impact of COVID-19 on cancer care in India: a cohort study.

BACKGROUND: The COVID-19 pandemic has disrupted health-care systems, leading to concerns about its subsequent impact on non-COVID disease conditions. The diagnosis and management of cancer is time sensitive and is likely to be substantially affected by these disruptions. We aimed to assess the impact of the COVID-19 pandemic on cancer care in India. METHODS: We did an ambidirectional cohort study at 41 cancer centres across India that were members of the National Cancer Grid of India to compare provision of oncology services between March 1 and May 31, 2020, with the same time period in 2019. We collected data on new patient registrations, number of patients visiting outpatient clinics, hospital admissions, day care admissions for chemotherapy, minor and major surgeries, patients accessing radiotherapy, diagnostic tests done (pathology reports, CT scans, MRI scans), and palliative care referrals. We also obtained estimates from participating centres on cancer screening, research, and educational activities (teaching of postgraduate students and trainees). We calculated proportional reductions in the provision of oncology services in 2020, compared with 2019. FINDINGS: Between March 1 and May 31, 2020, the number of new patients registered decreased from 112 270 to 51 760 (54% reduction), patients who had follow-up visits decreased from 634 745 to 340 984 (46% reduction), hospital admissions decreased from 88 801 to 56 885 (36% reduction), outpatient chemotherapy decreased from 173634 to 109 107 (37% reduction), the number of major surgeries decreased from 17 120 to 8677 (49% reduction), minor surgeries from 18 004 to 8630 (52% reduction), patients accessing radiotherapy from 51 142 to 39 365 (23% reduction), pathological diagnostic tests from 398 373 to 246 616 (38% reduction), number of radiological diagnostic tests from 93 449 to 53 560 (43% reduction), and palliative care referrals from 19 474 to 13 890 (29% reduction). These reductions were even more marked between April and May, 2020. Cancer screening was stopped completely or was functioning at less than 25% of usual capacity at more than 70% of centres during these months. Reductions in the provision of oncology services were higher for centres in tier 1 cities (larger cities) than tier 2 and 3 cities (smaller cities). INTERPRETATION: The COVID-19 pandemic has had considerable impact on the delivery of oncology services in India. The long-term impact of cessation of cancer screening and delayed hospital visits on cancer stage migration and outcomes are likely to be substantial. FUNDING: None. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

Multinational Study to Assess Stress Levels Among the Health Care Workers of Radiation Oncology Community at the Outset of the COVID-19 Pandemic.

PURPOSE: To evaluate stress levels among the health care workers (HCWs) of the radiation oncology community in Asian countries. METHODS: HCWs of the radiation oncology departments from 29 tertiary cancer care centers of Bangladesh, India, Indonesia and Nepal were studied from May 2020 to July 2020. A total of 758 eligible HCWs were identified. The 7-Item Generalized Anxiety Disorder, 9-Item Patient Health Questionnaire, and 22-Item Impact of Events Scale-Revised were used for assessing anxiety, depression, and post-traumatic stress disorder. Univariate and multivariate analysis was done to identify the causative factors affecting mental health. RESULTS: A total of 758 participants from 794 HCWs were analyzed. The median age was 31 years (IQR, 27-28). The incidence of moderate to severe levels of anxiety, depression, and stress was 34.8%, 31.2%, and 18.2%, respectively. Severe personal concerns were noticed by 60.9% of the staff. On multivariate analysis, the presence of commonly reported symptoms of COVID-19 during the previous 2 weeks, contact history (harzard ratio [HR], 2.04; CI, 1.15 to 3.63), and compliance with precautionary measures (HR, 1.69; CI, 1.19 to 2.45) for COVID-19 significantly predicted for increasing anxiety (HR, 2.67; CI, 1.93 to 3.70), depression (HR, 3.38; CI 2.36 to 4.84), and stress (HR, 2.89; CI, 1.88 to 4.43) (P < .001). A significant regional variation was also noticed for anxiety, stress, and personal concerns. CONCLUSION: This survey conducted during the COVID-19 pandemic revealed that a significant proportion of HCWs in the radiation oncology community experiences moderate to severe levels of anxiety, depression, and stress. This trend is alarming and it is important to identify and intervene at the right time to improve the mental health of HCWs to avoid any long-term impacts.

An assessment of serum oxidative stress and antioxidant parameters in patients undergoing treatment for cervical cancer.

OBJECTIVES: Oxidative stress and antioxidants are involved in all aspects of cervical cancer. The present study evaluated serum levels of oxidative stress and antioxidant biomarkers in cervical cancer patients and healthy controls. Moreover, the effect of Concurrent chemoradiotherapy (CCRT) on these biomarkers and their association with treatment outcome was investigated. DESIGN: This study included ninety-seven cervical cancer patients and thirty controls. Three oxidative stress parameters (8-hydroxy-2-deoxyguanosine, Protein Carbonyl, and Malondialdehyde) and four antioxidant parameters (Superoxide Dismutase, Catalase, Glutathione Peroxidase, and Total Antioxidant Status) were measured. The analysis was conducted using repeated measures ANOVA for comparing among the phases (before, during, and follow-up) of treatment. The control group was compared using the Dunnet test. Logistic regression analysis was also conducted between oxidative stress and antioxidant parameters to study their association. RESULTS: Significant rises in oxidative damage markers were observed in cervical cancer patients of all stages, compared to controls. There was a further increase in oxidative stress markers during CCRT among complete responders. However, among non-responders, the oxidative stress biomarkers like Protein Carbonyl and Malondialdehyde were unaltered during CCRT. Simultaneously, there was a significant decrease in antioxidant parameters in cervical cancer patients of all stages compared to controls. During CCRT, antioxidant levels continuously depleted among complete responders. Nevertheless, in non-responders, antioxidant parameters like Superoxide Dismutase and Total Antioxidant Status were consistent. The oxidative stress markers and antioxidant parameters normalized among complete responders at six months follow up. While in non-responders, the normalization of these parameters was not observed. CONCLUSION: Our results indicate that increased oxidative stress and diminished antioxidants among patients were associated with carcinoma cervix. Induced oxidative stress and decreased antioxidant parameters during CCRT among the complete responders show the treatment's efficacy. Oxidant-antioxidant profile merits investigation as markers of diagnosis, treatment response, survival, and recurrence in extensive prospective studies.

Diagnostic and prognostic application of Raman spectroscopy in carcinoma cervix: A biomolecular approach.

Blood serum samples from 63 cervical cancer patients and 30 controls were collected at three different phases of the treatment (i.e. before, during, and at follow up). The spectra of serum samples from control as well as patients were classified into different groups using principal component analysis (PCA) and linear discriminant analysis (LDA) based on different phases of treatment using R software. The spectra of blood serum samples have shown the distinct changes and differences compared with each other in the profile of various biochemical parameters. The sensitivity (92.5%) and specificity (85%) were observed maximum between control and cervical cancer patients (before treatment). Between different phases of treatment, the sensitivity and specificity were less but, all accuracies of detection and classification reached above 50%. This method can be considered as a screening method for detection and treatment monitoring.

A comparison between revised Manchester Point A and ICRU-89-recommended Point A definition absorbed-dose reporting using CT images in intracavitary brachytherapy for patients with cervical carcinoma.

PURPOSE: This study is a comparison between revised Manchester Point A and International Commission on Radiation Units and measurements (ICRU) 89 report-recommended Point A absorbed-dose reporting in intracavitary brachytherapy for patients with cervical carcinoma. METHODS AND MATERIALS: The retrospective dosimetric study is based on the data of 32 patients with cervical carcinoma treated with high-dose-rate brachytherapy. Patients received 21 Gy in three fractions (7.0 Gy X three fractions) to Point A (Aflange, revised Manchester definition). All the patients were replanned with a new Point A (Aicru89) defined on CT images as per the American Brachytherapy Society/ICRU-89. The data collected were compared with the data obtained from Point A (Aflange). RESULTS: When using the Aflange plan normalization method, the mean dose of 0.1 cc, 1 cc, and 2 cc bladder volumes was 820.79 ± 207.47 cGy, 654.66 ± 152.69 cGy, and 588.91 ± 136.35 cGy, respectively. Likewise, when using the ICRU-89 Point Aicru89 normalization method, the mean dose of 0.1 cc, 1 cc, and 2 cc bladder volumes was 869.30 ± 224.67 cGy, 693.24 ± 166.20 cGy, and 616.61 ± 150.32 cGy, respectively. For the rectum, Point Aflange normalization plans, the mean dose of 0.1 cc, 1 cc, and 2 cc volumes was 589.37 ± 163.26 cGy, 487.51 ± 126.03 cGy, and 442.70 ± 111.43 cGy, respectively. Likewise, using the Aicru89 plan, the mean 0.1 cc, 1 cc, and 2 cc rectum volume was 625.07 ± 171.31 cGy, 517.50 ± 131.05 cGy, 464.94 ± 121.81 cGy, respectively. The statistical mean difference of Total Reference Air Kerma rate, V100 (cc), bladder, rectum and sigmoid, was found significant. CONCLUSIONS: It has been found that the position of revised Manchester (Aflange) and ICRU-89 Point A does not match on CT images/radiograph, which resulted in variation in doses to the tumor, V100 (cc), organ at risk, and Total Reference Air Kerma.

Benzothiazole derivative bearing amide moiety induces p53-mediated apoptosis in HPV16 positive cervical cancer cells.

In our previous study, we screened the anti-cancer properties of 10 benzothiazole derivatives in cervical cancer cell lines. In the present study, we aimed to delineate the mechanism of the apoptotic pathway (whether intrinsic or extrinsic) following the treatment of N-(4-(benzo[d]thiazol-2-yl)phenyl)-5-chloro-2-methoxybenzamide (named as A-07) on cervical cancer cell lines. Cellular stress by reactive oxygen species was measured using DCFDA dye by flowcytometry. Protein expression and localization was checked by immunofluorescence for γH2A.X, TP53, and CASP-3. Expression profiles of BAX and BCL-2 was done by semi-quantitative RT-PCR and PARP-1 (Poly(ADP-ribose) polymerase-1) by Western blot analysis. Bioinformatic studies were done using PDB websites, metaPocket 2.0 server, YASARA software and Discovery Studio 3.5 Visualizer. We demonstrate that the compound A-07 leads to ROS generation and double strand breaks in SiHa and C-33A cells. The induction of apoptosis in SiHa cells is associated with increased nuclear expression of the tumor suppressor protein, TP53. The shift in BAX/BCL-2 ratio, increased expression of Caspase-3 and cleaved Poly(ADP-ribose) polymerase-1 favour apoptotic signal in SiHa. In silico studies revealed that A-07 has inhibiting capabilities to the E6/E6AP/P53 complex. Our data suggest that treatment of A-07 causes p53 and caspase dependent apoptosis in HPV 16 infected SiHa cells.

Search of an ideal location of isocenter in intensity-modulated radiotherapy treatment plans: A dosimetrical approach.

AIM: The aim of this study is to identify an ideal location of isocenter in intensity-modulated radiotherapy (IMRT) treatment plans. MATERIALS AND METHODS: A total of 28 clinical target volumes and 4 English capital letters (C, L, T, and H) target volumes were considered in this study. Two IMRT treatment plans were generated for each target volume in the ECLIPSETM treatment planning system (TPS), first one with isocenter automatically placed (ISOAUTO) by TPS and the second one with geometric center-based isocenter (ISOGEOM). The geometric center of a cuboid volume, which was formed encompassing around the target volume in sagittal, transverse, and frontal planes, is considered as the geometric center of the target volume as well as the isocenter (ISOGEOM) of the IMRT plans. While performing the IMRT treatment plans using the beam angle optimization and dose volume optimization, the normal tissue objectives and target volume objectives were kept similar in both the plans. The dosimetrical parameters between the two groups of plans were compared. RESULTS: The distance between ISOGEOM and ISOAUTO ranged from 0.16 cm to 3.04 cm with a mean and median of 0.85 cm and 0.69 cm, respectively. The ISOGEOM-based IMRT plans exhibited statistically significant advantages in total monitor units reduction (100% of cases, P ≤ 0.001), total number of field reduction (66% of cases, P ≤ 0.001), and reduction of patient mean dose (69% of cases, P ≤ 0.001) over ISOAUTO-based IMRT plans. The conformity index, homogeneity index and target mean dose were comparable between both group of plans. CONCLUSION: Significant dosimetrical advantages may be observed, when the geometric centroid of target volume is considered as isocenter of IMRT treatment plan.