A Prospective Questionnaire-Based Study Evaluating Genetic Literacy and Impact of Brief Educational Intervention Among Breast Cancer Patients in a Low- to Middle-Income Country.

INTRODUCTION: A significant proportion of breast cancer cases are hereditary and are potentially preventable. However, adoption of the preventive measures remains a significant challenge, particularly because of to lack of knowledge and awareness in low- to middle-income countries. METHODS: This prospective study conducted at a high-volume tertiary care cancer center in North India to assess the knowledge, awareness, and attitudes of female breast cancer patients and impact of a brief educational intervention. The study involved three phases: pre-interventional assessment, educational intervention, and post-interventional assessment utilizing a structured questionnaire. RESULTS: The study involved 300 newly diagnosed breast cancer patients; 16.7% were familial. At the outset, 87.0% patients had low knowledge of risk factors, 90.3% about screening, and 32.7% about treatment. Awareness levels were low: 13.7% aware of familial risk and 2.7% of breast cancer genes. Affordability of genetic testing was low (15.2%), and interest in testing for self and family members was limited (32.0% and 26.3%). Following educational intervention, a significant positive percentage change was noticed in knowledge (risk factors: 12.8%, screening: 36.2%, treatment: 82%), awareness (familial risk: 66.7%, BRCA gene: 12.3%), and attitude (testing for self: 17.8%, family: 19.5%). CONCLUSIONS: This study highlights the significant knowledge gaps among breast cancer patients regarding genetics. The educational intervention led to notable improvements in knowledge, awareness, and attitudes, underscoring the importance of tailored patient education in breast cancer care.

Combination of 3PO analog PFK15 and siPFKL efficiently suppresses the migration, colony formation ability, and PFK-1 activity of triple-negative breast cancers by reducing the glycolysis.

Among all the subtypes of breast cancer, triple-negative breast cancer (TNBC) has been associated with the worst prognosis. Recently, for many solid tumors (including breast cancer) metabolic reprogramming has appeared as a cancer cell hallmark, and the elevated glycolytic pathway has been linked to their aggressive phenotype. In the present study, we evaluated the prognostic and therapeutic relevance of PFKFB3 (6-phosphofructo-2- kinase/fructose-2,6-bisphosphatase) in TNBCs. Prognostic significance of PFKFB3 expression was evaluated in overall breast cancers as well as in TNBCs. PFKFB3 inhibitor (3PO potent analogue i.e., PFK15) cytotoxicity in TNBC cell lines (MDA-MB-231 and MDA-MB-468) was analyzed using an MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Cancer cell physiological characteristics like clonogenicity and migration were also investigated after PFK15 treatment. As fructose-2,6-bisphosphate (F-2,6-BP), has been associated with increased PFK-1 activity, the effect of PFKFB3 inhibition by PFK15 was investigated on two major isoforms of phosphofructokinase-1 (PFK-1) in breast cancer, that is, phosphofructokinase-platelet type (PFKP) and phosphofructokinase-liver type (PFKL) (relevant to breast cancer). For PFKL inhibition, the siRNA approach was used. PFKFB3 expression was significantly correlated with inferior overall survival in breast cancer patients including TNBCs. PFK15 treatment in TNBC cells (i.e., MDA-MB-231 and MDA-MB-468) resulted in a decreased PFKP expression, thereby leading to reduced colony formation ability, migration rate, and extracellular lactate levels. However, to our surprise PFK15 treatment in both TNBC cells also resulted in elevated PFKL levels. Our results demonstrated that the combinatorial inhibition of PFK15 with siPFKL was more effective in TNBC cells, as it led to a decrease in colony formation ability, migration rate, extracellular lactate levels, and PFK-1 activity when compared with individual treatments. Using bona fide PFKFB3 inhibitor, that is, AZ67, we further show that AZ67 treatment to TNBC cells has no effect either on the expression of PFKP and PFKL, or on the lactate production. In summary, our present in vitro study demonstrated that 3PO derived PFK15 mechanism of action is totally different from AZ67 in TNBC cells. However, we advocate that the PFK15-mediated inhibition (along with PFKL) on the TNBCs migration, colony formation, and PFK-1 activity can be further explored for the therapeutic advantage of TNBC patients.

Ubiquitin specific peptidase 37 and PCNA interaction promotes osteosarcoma pathogenesis by modulating replication fork progression.

BACKGROUND: Osteosarcoma is a type of bone cancer that predominantly affects young individuals, including children and adolescents. The disease progresses through heterogeneous genetic alterations, and patients often develop pulmonary metastases even after the primary tumors have been surgically removed. Ubiquitin-specific peptidases (USPs) regulate several critical cellular processes, such as cell cycle progression, transcriptional activation, and signal transduction. Various studies have revealed the significance of USP37 in the regulation of replication stress and oncogenesis. METHODS: In this study, the Cancer Genome Atlas (TCGA) database was analyzed to investigate USP37 expression. RNA sequencing was utilized to assess the impact of USP37 overexpression and depletion on gene expression in osteosarcoma cells. Various molecular assays, including colony formation, immunofluorescence, immunoprecipitation, and DNA replication restart, were employed to examine the physical interaction between USP37 and PCNA, as well as its physiological effects in osteosarcoma cells. Additionally, molecular docking studies were conducted to gain insight into the nature of the interaction between USP37 and PCNA. Furthermore, immunohistochemistry was performed on archived tissue blocks from osteosarcoma patients to establish a correlation between USP37 and PCNA expression. RESULTS: Analysis of the TCGA database revealed that increased expression of USP37 was linked to decreased progression-free survival (PFS) in osteosarcoma patients. Next-generation sequencing analysis of osteosarcoma cells demonstrated that overexpression or knockdown of USP37 led to the expression of different sets of genes. USP37 overexpression provided a survival advantage, while its depletion heightened sensitivity to replication stress in osteosarcoma cells. USP37 was found to physically interact with PCNA, and molecular docking studies indicated that the interaction occurs through unique residues. In response to genotoxic stress, cells that overexpressed USP37 resolved DNA damage foci more quickly than control cells or cells in which USP37 was depleted. The expression of USP37 varied in archived osteosarcoma tissues, with intermediate expression seen in 52% of cases in the cohort examined. CONCLUSION: The results of this investigation propose that USP37 plays a vital role in promoting replication stress tolerance in osteosarcoma cells. The interaction between USP37 and PCNA is involved in the regulation of replication stress, and disrupting it could potentially trigger synthetic lethality in osteosarcoma. This study has expanded our knowledge of the mechanism through which USP37 regulates replication stress, and its potential as a therapeutic target in osteosarcoma merits additional exploration.

Primary Mediastinal Germ Cell Tumors (PMGCT): A Real-world Analysis From A Tertiary Cancer Care Center in India.

BACKGROUND: Primary mediastinal GCT (PMGCT) is a rare entity and comprises 10-15% of all mediastinal tumors. We present our institutional experience of MGCT treated with multimodality management. MATERIALS AND METHODS: We conducted a retrospective analysis between 2010 to 2020 of all mediastinal germ cell tumors registered at our center. Data on patient demographics, treatments received, treatment toxicities and response were recorded. Overall survival and relapse free survival were estimated using Kaplan-Meier methods. RESULTS: A total of 30 patients were identified. The median age was 25.5 (range, 18-45) years. Common presenting features included cough (70%) and shortness of breath (70%). Histology wise, 60% patients were non seminomatous histology, whereas 33.3% patients were Seminoma. Twenty-seven (90%) patients received chemotherapy as the first-line treatment, of whom five patients (16.6%) underwent surgery and radiation therapy subsequently. Median follow-up was 26.9 months. Thirteen patients (43.3%) had complete response (43.3%) and eight patients had partial response (26.7%), while three patients (5.5%) had progressive disease. Three-year relapse-free survival rate was 69.6% (95% confidence interval [CI], 42.8-85.6%). Overall survival (OS) at 3 years was 73.4% (95% CI, 49.4-87.3%). Patients with seminoma had a 3 year OS of 90.0% (95% CI, 47.3-98.5%) compared to those with non-seminoma (63.53% [95% CI, 32.3-83.3%]). CONCLUSIONS: Multiagent chemotherapy is the backbone of treatment in PMGCT. Seminomatous PMGCT have excellent prognosis, while further improvement is needed in those with nonseminomatous tumor.

Whole exome sequencing identifies novel variants of PIK3CA and validation of hotspot mutation by droplet digital PCR in breast cancer among Indian population.

BACKGROUND: Breast cancer (BC) is the most common malignancy with very high incidence and relatively high mortality in women. The PIK3CA gene plays a pivotal role in the pathogenicity of breast cancer. Despite this, the mutational status of all exons except exons 9 and 20 still remains unknown. METHODS: This study uses the whole exome sequencing (WES) based approach to identify somatic PIK3CA mutations in Indian BC cohorts. The resultant hotspot mutations were validated by droplet digital PCR (ddPCR). Further, molecular dynamics (MD) simulation was applied to elucidate the conformational and functional effects of hotspot position on PIK3CA protein. RESULTS: In our cohort, PIK3CA showed a 44.4% somatic mutation rate and was among the top mutated genes. The mutations of PIK3CA were confined in Exons 5, 9, 11, 18, and 20, whereas the maximum number of mutations lies within exons 9 and 20. A total of 9 variants were found in our study, of which 2 were novel mutations observed on exons 9 (p.H554L) and 11 (p.S629P). However, H1047R was the hotspot mutation at exon 20 (20%). In tumor tissues, there was a considerable difference between copy number of wild-type and H1047R mutant was detected by ddPCR. Significant structural and conformational changes were observed during MD simulation, induced due to point mutation at H1047R/L position. CONCLUSIONS: The current study provides a comprehensive view of novel as well as reported single nucleotide variants (SNVs) in PIK3CA gene associated with Indian breast cancer cases. The mutation status of H1047R/L could serve as a prognostic value in terms of selecting targeted therapy in BC.

No Doppler Single Position-Lateral Intercostal Artery Perforator Flap (NDSP-LICAP): a Safe and Versatile Flap for Breast Oncoplasty in Resource-Limited Setting.

INTRODUCTION: The lateral intercostal artery perforator flap (LICAP) has emerged as one of the safest and less morbid flaps for lateral and central breast defects. We hereby describe a reproducible no Doppler single position (NDSP) technique to harvest it in single position without handheld Doppler, making it a versatile flap for lateral breast defects in resource-limited setting also. MATERIALS AND METHODS: With this technique, we performed a total of 22 LICAP turnover flaps over a period of 18 months from January 2020 to June 2021. In all 22 cases, the indication of flap was to fill the post-breast conservation surgery (BCS) defects in outer quadrant of breast. All LICAP flaps were harvested by surface marking of anatomical landmarks and without handheld Doppler. RESULTS: Out of 22 LICAP turnover flaps, thirteen were harvested for left breast and nine for right breast. The median width and length of the flap were 12.2 cm and 19.6 cm, respectively. The additional mean operative time was 41 min. All LICAP flaps survived well, and grade 1 Clavien-Dindo morbidity was documented in four cases. Mean hospital stay was 2.6 days. All patients received radiotherapy on their stipulated schedule. Early cosmetic outcome was good, and long-term outcomes are awaited. CONCLUSION: NDSP-LICAP flap is a workhorse for lateral breast defects. Precise knowledge of perforators and anatomical landmarks can be used for harvesting these flaps, thus avoiding ultrasound Doppler and dedicated training for perforator localization. This technique has short learning curve without the need for any plastic surgery training. The early cosmetic outcomes are good.

Profile of Pathogenic Mutations and Evaluation of Germline Genetic Testing Criteria in Consecutive Breast Cancer Patients Treated at a North Indian Tertiary Care Center.

BACKGROUND: The burden of hereditary breast cancer in India is not well defined. Moreover, genetic testing criteria (National Comprehensive Cancer Network [NCCN] and Mainstreaming Cancer Genetics [MCG] Plus) have never been validated in the Indian population. METHODS: All new female breast cancer patients from 1st March 2019 to 28th February 2020 were screened. Those providing informed consent and without previous genetic testing were recruited. Multigene panel testing (107 genes) by next-generation sequencing was performed for all patients. The frequency of pathogenic/likely pathogenic (P/LP) mutations between patients qualifying and not qualifying the testing criteria was compared and their sensitivity was computed. RESULTS: Overall, 275 breast cancer patients were screened and 236 patients were included (median age 45 years); 30 patients did not consent and 9 patients previously underwent genetic testing. Thirty-four (14%) women had a positive family history and 35% had triple-negative breast cancer. P/LP mutations were found in 44/236 (18.64%) women; mutations in BRCA1 (22/47, 46.8%) and BRCA2 (9/47, 19.1%) were the most common, with 34% of mutations present in non-BRCA genes. Patients qualifying the testing criteria had a higher risk of having a P/LP mutation (NCCN: 23.6% vs. 7.04%, p = 0.03; MCG plus: 24.8% vs. 7.2%, p = 0.01). The sensitivity of the NCCN criteria was 88.6% (75.4-96.2) and 86.36% (72.65-94.83) for MCG plus. More than 95% sensitivity was achieved if all women up to 60 years of age were tested. Cascade testing was performed in 31 previous (16/44 families), with 23 testing positive. CONCLUSIONS: The frequency of P/LP mutations in India is high, with significant contribution of non-BRCA genes. Testing criteria need modification to expand access to testing.

Characteristics & outcomes of cancer patients with COVID-19: A multicentre retrospective study from India.

Background & objectives: High mortality has been observed in the cancer population affected with COVID-19 during this pandemic. We undertook this study to determine the characteristics and outcomes of cancer patients with COVID-19 and assessed the factors predicting outcome. Methods: Patients of all age groups with a proven history of malignancy and a recent diagnosis of SARS-CoV-2 infection based on nasal/nasopharyngeal reverse transcriptase (RT)-PCR tests were included. Demographic, clinical and laboratory variables were compared between survivors and non-survivors groups, with respect to observed mortality. Results: Between May 11 and August 10, 2020, 134 patients were included from the three centres and observed mortality was 17.1 per cent. The median age was 53 yr (interquartile range 39-61 yr) and thirty four patients (25%) were asymptomatic. Solid tumours accounted for 69.1 per cent and breast cancer was the most common tumour type (20%). One hundred and five patients (70.5%) had received chemotherapy within the past four weeks and 25 patients (19.3%) had neutropenia at presentation. On multivariate analysis, age [odds ratio (OR) 7.99 (95% confidence interval [CI] 1.18-54.00); P=0.033], haemoglobin [OR 6.28 (95% CI 1.07-37.04); P=0.042] neutrophil-lymphocyte ratio [OR 12.02 (95% CI 2.08-69.51); P=0.005] and baseline serum albumin [OR 18.52 (95% CI 2.80-122.27); P=0.002], were associated with higher mortality. Recent chemotherapy, haematological tumours type and baseline neutropenia did not affect the outcome. Interpretation & conclusions: Higher mortality in moderate and severe infections was associated with baseline organ dysfunction and elderly age. Significant proportion of patients were asymptomatic and might remain undetected.

Factors associated with the initiation of chemotherapy within 90 days of death in metastatic colorectal cancer patients: a population-based study.

INTRODUCTION: Initiation of chemotherapy in patients with cancer near end-of-life (EOL) has become more frequent due to an increasing number of treatment options. We aimed to analyze the proportion of metastatic colorectal cancer patients (mCRC) in Alberta, Canada, who were started on a new chemotherapy regimen within 90 days of death. METHODS: This was a retrospective, population-based study using data from the cancer measurement outcomes and evaluation (C-MORE) database. All patients who received chemotherapy for mCRC in a large Canadian province from January 1, 2011, to December 31, 2016, were included in the current analysis. We identified the proportion of patients who initiated chemotherapy near EOL. Further, we analyzed the associations of baseline factors with initiation of chemotherapy near EOL. RESULTS: We identified 511 patients with mCRC who received chemotherapy. Of these, 132 (25.8%) initiated chemotherapy near EOL. Charlson's comorbidity index (CCI) score (score 1: OR, 0.524; 95% CI, 0.279-0.985; P = 0.045; CCI score > 1: OR, 0.366; 95% CI, 0.180-0.746; P = 0.006) and Eastern cooperative oncology group performance status (ECOG PS) (ECOG PS 2: OR, 4.457; 95% CI 2.518-7.890; P < 0.0001; ECOG PS > 2: OR 7.725; 95% CI 3.465-17.222; P < 0.0001) were predictive of initiation of chemotherapy near EOL. The most frequent chemotherapy regimens initiated were FOLFIRI (17%), capecitabine (15%), and panitumumab (15%), respectively. CONCLUSIONS: Chemotherapy is frequently initiated near EOL in patients with mCRC. Routine clinical assessments including ECOG PS and comorbid medical conditions can help select patients with mCRC who are unlikely to benefit from palliative chemotherapy and prevent the adverse events and healthcare costs associated with such interventions near EOL.

Associations between baseline symptom burden as assessed by patient-reported outcomes and overall survival of patients with metastatic cancer.

BACKGROUND: Serial symptom assessments using patient-reported outcomes may be challenging to implement in routine clinical practices. We aimed to determine if a single measurement of symptom burden at the time of metastatic diagnosis is associated with survival. METHODS: We examined baseline patient-reported outcomes (within 90 days of diagnosis) of patients newly diagnosed with metastatic breast, lung, colorectal, or prostate cancer using the revised Edmonton Symptom Assessment System (ESASr) questionnaire. The ESASr was categorized into physical, psychological, and total symptom domains whereby scores were classified as none to mild (0-3) or moderate to severe (4-10). Multivariable Cox proportional hazards models were constructed to evaluate the effect of baseline symptom scores on overall survival. RESULTS: We identified 1316 patients eligible for analysis. There were 181, 601, 240, and 294 patients with breast, lung, colorectal, and prostate cancer, respectively. Approximately one-quarter of all patients reported moderate to severe physical, psychological, and total symptom subscores. On multivariable Cox regression analysis, older age (P < 0.001), male sex (P = 0.002), primary lung cancer (P < 0.001), and smoking in the previous month (P = 0.007) were predictive of inferior overall survival as were baseline moderate to severe physical (hazard ratio, 1.49; 95% confidence interval, 1.16-1.90; P = 0.002) and total symptom subscores (hazard ratio, 1.38; 95% confidence interval, 1.06-1.81; P = 0.017). CONCLUSIONS: A single assessment of baseline symptom burden using the ESASr in patients with metastatic cancer has significant prognostic value. This may represent a feasible first step towards routine collection of patient-reported outcomes in real-world settings where serial symptom measurements can be challenging to implement.

Symptom burden in patients with common cancers near end-of-life and its associations with clinical characteristics: a real-world study.

BACKGROUND: Patients dying with cancer can experience various physical and psychological symptoms. We aimed to determine the type and severity of symptoms within the last 6 months of life in a large real-world cohort of patients with cancer. METHODS: We examined prospectively collected patient-reported outcomes of patients with lung, colorectal, breast, prostate or pancreatic cancer using the revised Edmonton Symptom Assessment System (ESASr) questionnaire from a large province in Canada from 2016 to 2017. The ESASr was categorized into physical and psychological symptom subscores and total symptom score, and each was classified as none to mild (0-3) or moderate to severe (4-10) based on intensity. Multivariable logistic regression analyses were performed to evaluate the relationship between clinical characteristics and symptom scores. RESULTS: We identified 1159 patients eligible for analysis, of whom 52.2% were men and median age was 68 years. There were 613, 192, 149, 111 and 94 patients with lung, colorectal, breast, prostate and pancreatic cancer, respectively. While approximately half of patients reported moderate to severe physical symptom subscores and total symptom scores, only one-third reported moderate to severe psychological subscores. On multivariable logistic regression analyses, women were more likely to report moderate to severe physical (odds ratio [OR], 1.52; 95% confidence interval [CI], 1.08-2.12; P = 0.016), psychological (OR, 1.60; 95% CI, 1.14-2.26; P = 0.006) and total symptom scores (OR, 1.80; 95% CI, 1.28-2.51; P = 0.001). Patients with lung cancer were also more likely to report moderate to severe physical and psychological subscores (OR, 1.95; 95% CI, 1.28-2.96; P = 0.002 and OR, 1.78; 95% CI, 1.13-2.81; P = 0.013) and total symptom scores (OR, 1.83; 95% CI, 1.20-2.81; P = 0.005). Finally, those closer to death were more likely to report moderate to severe physical symptom subscores (OR, 2.07; 95% CI, 1.33-3.23; P = 0.001) and total symptom scores (OR, 2.29; 95% CI, 1.46-3.60; P < 0.001), but not psychological symptom scores (OR, 1.34; 95% CI, 0.84-2.14; P = 0.210). CONCLUSIONS: There is significant symptom burden in patients with cancer near the end-of-life. Further, physical symptoms appear to be more intense than psychological symptoms. Symptom-directed care is still needed to improve the quality of end-of-life.

Patient-Reported Symptom Burden Near the End of Life in Patients With Gynaecologic Cancers.

OBJECTIVE: There are limited data on patient-reported outcomes near the end of life in patients with gynaecologic cancers. This study aimed to assess the symptom burden in the last 6 months of life in a real-world cohort. METHODS: Patients diagnosed with metastatic gynaecologic malignancies from 2016 to 2019 who completed the revised Edmonton Symptom Assessment System (ESASr) questionnaire within 6 months of death in a large Canadian province were identified. Patient-reported symptom scores were categorized as none to mild (0-3) and moderate to severe (4-10). Individual symptoms were subsequently grouped into physical, psychological, and total subscores. The severity of symptoms was further analyzed for any associations with age, time to death, and primary tumour site (ovarian vs. uterocervical and vulvovaginal). RESULTS: We identified 107 patients with gynaecologic malignancies including 59 ovarian, 29 uterocervical, and 19 vulvovaginal cancers. The median ages at diagnosis and questionnaire completion were 64 and 65 years, respectively. The median time from completing the ESASr questionnaire to death was 65 days. Overall, physical and psychological symptoms were moderate to severe in 57.9% and 40.2% of patients, respectively. Among the individual symptoms, tiredness was the most commonly reported moderate to severe symptom (74.9%), while shortness of breath was least commonly reported (31.6%). While physical (P < 0.001) and total symptom (P = 0.009) subscores were more likely to be moderate to severe in intensity as death approached, the psychological subscore (P = 0.744) had no relationship with time to death. Longer time to death was predictive of lower physical (P = 0.002) and total symptom (P = 0.002) subscores, while a primary uterocervical cancer site was associated with a lower psychological symptom subscore (P = 0.042). CONCLUSIONS: In the real-world setting, unique symptom trajectories can emerge for patients with gynaecologic cancer near the end of life. Knowledge of these specific symptom patterns can help inform the development and delivery of targeted palliative interventions to improve quality of life for these patients.

Prognostic Value of Serum Procalcitonin Levels in Patients With Febrile Neutropenia Presenting to the Emergency Department.

BACKGROUND: Various risk-stratification scores have been developed to identify low-risk febrile neutropenia (FN). The Multinational Association of Supportive Care in Cancer (MASCC) score is a commonly used validated scoring system, although its performance varies due to its subjectivity. Biomarkers like procalcitonin (PCT) are being used in patients with FN to detect bacteremia and additional complications. OBJECTIVE: Our objective was to compare the performance of MASCC score with PCT in predicting adverse outcomes in patients with FN. METHODS: This was a prospective observational study that included chemotherapy-induced FN in hematologic or solid malignancy. The MASCC score, PCT levels, and blood cultures were taken at the first point of contact, and patient treatment was managed according to routine institutional protocol. The primary outcome was mortality at 30 days. RESULTS: A total of 100 patients were recruited, of which 92 had hematologic malignancy and 8 had solid malignancy. Forty-six patients were classified as low risk by MASCC score (≥21). The PCT threshold, 1.42 ng/mL, was taken as a cutoff value, with area under the receiver operating characteristic curve (AUROC) of 0.664 (95% confidence interval [CI] -0.55 to 0.77) for predicting mortality. AUROC for MASCC was 0.586 (95% CI 0.462 to 0.711). CONCLUSIONS: PCT is a useful marker with better prognostic efficacy than MASCC score in patients with FN and can be used as an adjunct to the score in risk-stratifying patients with FN.

Impact of pre-existing cardiovascular disease on treatment patterns and survival outcomes in patients with lung cancer.

BACKGROUND: Baseline cardiovascular disease (CVD) can impact the patterns of treatment and hence the outcomes of patients with lung cancer. This study aimed to characterize treatment trends and survival outcomes of patients with pre-existing CVD prior to their diagnosis of lung cancer. METHODS: We conducted a retrospective, population-based cohort study of patients with lung cancer diagnosed from 2004 to 2015 in a large Canadian province. Multivariable logistic regression and Cox regression models were constructed to determine the associations between CVD and treatment patterns, and its impact on overall (OS) and cancer-specific survival (CSS), respectively. A competing risk multistate model was developed to determine the excess mortality risk of patients with pre-existing CVD. RESULTS: A total of 20,689 patients with lung cancer were eligible for the current analysis. Men comprised 55%, and the median age at diagnosis was 70 years. One-third had at least one CVD, with the most common being congestive heart failure in 15% of patients. Pre-existing CVD was associated with a lower likelihood of receiving chemotherapy (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.48-0.58; P < .0001), radiotherapy (OR, 0.76; 95% CI, 0.7-0.82; P < .0001), and surgery (OR, 0.56; 95% CI, 0.44-0.7; P < .0001). Adjusting for measured confounders, the presence of pre-existing CVD predicted for inferior OS (hazard ratio [HR], 1.1; 95% CI, 1.1-1.2; P < .0001) and CSS (HR, 1.1; 95% CI, 1.1-1.1; P < .0001). However, in the competing risk multistate model that adjusted for baseline characteristics, prior CVD was associated with increased risk of non-cancer related death (HR, 1.48; 95% CI, 1.33-1.64; P < 0.0001) but not cancer related death (HR, 0.98; 95% CI, 0.94-1.03; P = 0.460). CONCLUSIONS: Patients with lung cancer and pre-existing CVD are less likely to receive any modality of cancer treatment and are at a higher risk of non-cancer related deaths. As effective therapies such as immuno-oncology drugs are introduced, early cardio-oncology consultation may optimize management of lung cancer.

Factors Affecting Overall Survival in Premenopausal Women With Uterine Leiomyosarcoma: A Retrospective Analysis With Long-Term Follow-Up.

OBJECTIVE: Premenopausal women with uterine leiomyosarcoma experience different issues than menopausal women with this malignancy. This study evaluated the clinical profile and factors affecting survival outcomes in premenopausal women with uterine leiomyosarcoma. METHODS: We conducted a retrospective analysis of patients with uterine leiomyosarcoma, diagnosed between January 2008 and December 2016. Data were collected from the Alberta Cancer Registry, which reflects all patients in the province. Thirty-eight patients were included in the study, of whom 21 were alive on the last date of review (31 December, 2019). RESULTS: The median follow-up period was 86 months. Mean patient age was 44.6 ± 5.7 years. The 5-year survival rate was 34.2%; 45% of patients presented with stage I or II disease and 55%, with stage III or IV. There was no clinical suspicion of malignancy prior to surgery in about 60% of cases. Ovarian preservation was performed in about 34% of cases. Forty-five percent of patients had received chemotherapy and 26%, radiotherapy. Almost 90% had unspecified leiomyosarcoma. Univariate analysis of factors likely to affect overall survival showed that older age at diagnosis (HR 1.19; 95% CI 1.05-1.34, P = 0.005), lymphovascular invasion (HR 9.81; 95% CI 2.88-33.51, P = 0.00), and no radiation therapy (HR 2.60; 95% CI 0.99-6.87, P = 0.05) were associated with worse overall survival. A multivariate analysis of these risk factors showed only lymphovascular invasion of the tumour to be a significant risk factor affecting overall survival. (HR 18.07; 95% CI 4.23-77.15, P =0.00). CONCLUSION: Multivariate analysis showed lymphovascular invasion of tumour to be a significant risk factor affecting overall survival in premenopausal women with uterine leiomyosarcoma. Ovarian preservation, lymph node positivity, age, treatment strategy, hormone receptor status, and grade of tumour were not found out to be significant prognostic variables.

Association of energy intake and expenditure with obesity: A cross-sectional study of 150 pediatric patients following treatment for leukemia.

Increased obesity in leukemia survivors has been attributed to chemotherapy and radiation. Data on total energy intake (TEI) and total energy expenditure (TEE) are lacking in obese childhood leukemia patients after completion of therapy from India. We conducted a cross-sectional study in pediatric acute leukemia patients after completion of therapy wherein energy intake was assessed by 24-hour recall method. TEE was calculated using Harris-Benedict equation, by assessing the physical activity level using Physical Activity Questionnaire for children and basal metabolic rate by World Health Organization equation. Indian Academy of Pediatrics 2015 guidelines for BMI were used for defining overweight and obesity. Nutritional status was assessed in 150 leukemia patients after completion of therapy. Twenty-five percent of leukemia patients after completion of therapy were overweight and obese versus 11% of healthy controls (p = 0.042). The mean ratio of TEI/required energy intake (REI), TEE/required energy expenditure (REE), and (TEI:REI)/(TEE:REE) were significantly higher in overweight and obese group versus nonobese survivors (p < 0.001, p = 0.091, p < 0.001, respectively). Multivariate analysis showed higher income (HR-2.3, p = 0.04), increased TEI/REI (HR-4, p = 0.049) and higher (TEI:REI)/(TEE:REE) (HR-3.1, p = 0.039) to be significant factors predicting obesity. Obesity in leukemia patients after completion of therapy is associated with increased energy intake, causing imbalance between energy intake and TEE in these patients.

Parents' Perspective of Quality of Life of Retinoblastoma Survivors.

Health-related quality of life (HRQOL) in retinoblastoma survivors was assessed using parent proxy report of PedsQL(TM) 4.0 generic core scale. One hundred twenty-two parents of retinoblastoma survivors filled the questionnaire satisfactorily. This was compared with parent-reported HRQOL of 50 siblings. The median age of survivors was 98 (range, 60-247) months and male:female ratio was 2:1. The overall parent-reported HRQOL was significantly worse in survivors as compared to controls (74.4 ± 8.5 vs. 85.1 ± 4.6, P < 0.001). All health domains were significantly affected when compared with controls. None of the baseline and treatment-related factors predicted HRQOL.