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Background: Carcinoma penis is a rare neoplasm, and the literature is scarce on long-term survival and its predictors. The aim of the study was to determine the clinical profile and management patterns, identify predictors of survival, and the impact of education and rural/urban dwelling on survival. Methods: Patients with a histological diagnosis of carcinoma penis from January 2015 to December 2019 were included in the study. Demographics, clinical profile, education status, primary residence address, and outcomes were obtained from the case records. Distance from the treatment centre was obtained from the postal code. The primary objectives were to assess relapse-free survival (RFS) and overall survival (OS). The secondary objectives were to identify the predictors of RFS and OS and to determine the clinical profile and treatment patterns in patients with carcinoma penis in India. Time-to-event was calculated by Kaplan–Meir analysis and survival was compared by the log-rank test. Univariate and multivariable Cox regression analyses were used to find independent predictors of relapse and mortality. Logistic regression analyses to examine the associations of rural residence, education status, and distance from the treatment centre with the relapse adjusting for measured confounding variables. Results: Case records of 102 patients treated during the above period were retrieved. The median age was 55.5 (interquartile range [IQR] 42–65 years). Ulcero-proliferative growth (65%), pain (57%), and dysuria (36%) were the most common presenting features. Clinical examination or imaging revealed inguinal lymphadenopathy in 70.6% of patients, however, only 42% of these lesions were pathologically involved. A total of 58.8% of patients were from rural areas, 46.9% had no formal education, and 50.9% had a primary residence ≥100 km from the hospital. Patients with lower education and rural households had higher TNM stages and nodal involvement. Median RFS and OS were 57.6 months (15.8 months to not reached) and 83.9 months (32.5 months to not reached), respectively. On univariate analysis tumor stage, involvement of lymph nodes, T stage, performance status, and albumin was predictive for relapse and survival. However, on multivariate analysis, the stage remained the only predictor of RFS and nodal involvement, and metastatic disease was a predictor of OS. Education status, rural habitation, and distance from the treatment centre were not predictors for relapse or survival. Conclusions: Patients with carcinoma have locally advanced disease at presentation. Rural dwellings and lower education were associated with the advanced stage but did not have a significant bearing on the survival outcomes. The stage at diagnosis and nodal involvement is the most important predictor of RFS and OS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Peripheral neuropathy is a common dose-limiting side effect of paclitaxel. To date, there is no effective strategy to prevent paclitaxel-induced peripheral neuropathy. A recent small phase II study demonstrated the potential role of oral gabapentin in this setting. This phase III study is aimed to assess the efficacy of oral gabapentin in preventing paclitaxel-induced neuropathy. Objective: To compare the efficacy of oral gabapentin with placebo in preventing clinically significant peripheral neuropathy (NCI CTCAEv5.0 grade 2 or higher) in patients receiving paclitaxel. Methods: This is a randomized, placebo-controlled, double-blind, parallel-group superiority trial. The primary outcome is the development of grade 2 or higher chemotherapy-induced peripheral neuropathy. Secondary outcomes include any grade neuropathy, the percentage change in sensory nerve conduction velocities in peripheral nerves, time to development of any grade neuropathy, paclitaxel dose reductions and delays due to peripheral neuropathy, patient-reported outcomes, adverse events, and adherence to oral therapy. A total of 136 patients receiving paclitaxel will be randomly allocated (stratified by weekly vs. non-weekly administration) to receive either oral gabapentin or placebo till three weeks after the last dose of chemotherapy or occurrence of the primary outcome. Conclusion: This study aims to find if oral gabapentin reduces the incidence of grade 2 or higher chemotherapy-induced peripheral neuropathy in patients receiving paclitaxel. Trial registration: The trial is registered prospectively with the Clinical Trials Registry of India (CTRI/2022/02/040030) on April 4, 2022. [ABSTRACT FROM AUTHOR]

Renal cell carcinomas accounts for 2% of all the cancers globally. Most of the renal tumors are detected incidentally. Ultrasound remains the main screening modality to evaluate the renal masses. A multi -phase contrast enhanced computer tomography is must for characterizing the renal lesions. Imaging plays an important role in staging, treatment planning and follow up of renal cancers. In this review , we discuss the imaging guidelines for the management of renal tumors. [ABSTRACT FROM AUTHOR]

Background: The spectrum and significance of Variants of Uncertain Significance (VUS) mutations in breast cancer predisposition genes is poorly defined in the Indian population. Methods: All new female breast cancer patients from 1 March 2019 to 28 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. Descriptive statistics was used to describe the spectrum of VUS mutations. Results: Out of 236 patients recruited in the study, a VUS was detected in 89 patients (37.71%). VUS pathogenic ratio was 2.02. A total of 121 different VUS mutations in 40 different genes were detected. Fourteen patients (15.7%) had a VUS in high penetrance genes and 36 VUS mutations (29.8%) were detected in one of the genes involved in homologous recombination repair pathway. No therapeutic interventions were done based on VUS. Conclusions: In this large prospective study of genetic determinants of breast cancer from India, a high prevalence of VUS (37.71%) was detected with 15.7% patients having a VUS in high penetrance genes. More evidence needs to be generated from larger multicentric studies to better understand the implications of these genetic variants and enable their reclassification. [ABSTRACT FROM AUTHOR]

Introduction: Hand-foot syndrome (HFS) is a common cutaneous side effect of capecitabine therapy. Apart from oral cyclooxygenase-2 (COX-2) inhibitor (celecoxib), there are no proven strategies for the prevention of HFS. However, celecoxib is associated with significant cardiotoxicity. To date, no study has evaluated the role of topical COX inhibitor, diclofenac. In this study, we aim to compare topical 1% diclofenac gel with placebo in the prevention of capecitabine-induced HFS.Methods: This is a randomized, placebo-controlled, double-blind, parallel-group superiority trial: the Diclofenac Topical in Reducing Capecitabine induced HFS (D-TORCH) study. A total of 264 patients with breast and gastrointestinal malignancies will be randomly allocated (stratified by sex and type of therapy [monotherapy or combination regimen with capecitabine]) to receive either 1% topical diclofenac or placebo that will be applied over the palmar and dorsal surface of the hands twice daily whilst taking capecitabine for 12 weeks. The patients will be followed up until the end of four cycles. The primary objective of this study is to compare the effect of topical diclofenac with placebo in preventing HFS (incidence of NCI CTCAEv5.0 grade 2 or higher HFS). The secondary objective is to compare the effect of topical diclofenac with placebo on preventing all grades of HFS (incidence of NCI CTCv5.0 all grade HFS), time to develop HFS (from the start of capecitabine), patient-reported outcomes (PROs) (HF-HRQoL questionnaire), adherence with the application (self-reported), capecitabine dose changes (number of patients with dose modifications due to HFS) and safety profile (NCICTCv5.0 all grade HFS) DISCUSSION: The D-TORCH study aims to determine if 1% topical diclofenac reduces the incidence of grade 2 or higher HFS in patients receiving capecitabine. To date, there have been a lot of trials for hand-foot syndrome prevention using agents like pyridoxine, vitamin E, carvedilol, and various polyherbal formulations, but none has been found successful. If the trial meets the primary end point, 1% topical diclofenac will be the new standard of care for HFS prevention.Trial Registration: Clinical Trials Registry of India  CTRI/2021/01/030592 . Prospectively registered on January 19, 2021. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Hand foot skin reaction (HFSR) is a common dose-limiting adverse effect of multi kinase inhibitors (MKI) whose mechanism is not fully understood, and the prophylaxis is inadequate. In this pilot study, a double-blind, randomized placebo-controlled trial was conducted to evaluate the effect of topical urea in secondary prevention of sunitinib-induced HFSR in renal cell cancer patients. Out of 55 screened patients, 14 were randomized to receive topical urea or placebo for four weeks. The association of HFSR with drug levels of sunitinib and its metabolite (n-desethyl sunitinib), genetic polymorphism of VEGFR2 gene, quality of life (QOL) and biochemical markers was also assessed. The results showed that urea-based cream was not superior to placebo (P =.075). There was no change in the QOL in both the groups. Single nucleotide polymorphism was checked for two nucleotides rs1870377 and rs2305948 located in VEGFR2 gene on chromosome 4. SNP (variant T > A) at rs1870377 was associated with appearance of new HFSR as compared to the wild type, although the association was not statistically significant (OR 0.714). There was no statistically significant difference between mean plasma levels of sunitinib and N-desethyl sunitinib in urea arm as compared to placebo arm as compared to placebo. The best fit population pharmacokinetic model for sunitinib was one compartment model with first order absorption and linear elimination. The median (IQR) of population parameters calculated from the population pharmacokinetics model for Ka, V and Cl was 0.22 (0.21-0.24) h-1, 4.4 (4.09-4.47) L, 0.049 (0.042-0.12) L/hr, respectively. The study suggested that the urea-based cream was not superior to placebo in decreasing the appearance of new HFSR in renal cancer patients receiving 4:2 regimen of sunitinib. In this randomized, placebo-controlled trial, urea cream was found to be non-superior to placebo in prevention of hand-foot skin reaction with no change in QoL. SNP at rs1870377 was associated with appearance of new HFSR. There was no difference between the plasma levels of sunitinib and n-desethyl sunitinib. The best-fit popPK model was one-compartment with first-order absorption and linear elimination. [ABSTRACT FROM AUTHOR]

Background: Nasotracheal intubation (NTI) is commonly performed in oromaxillofacial surgeries. We did this meta-analysis to ascertain whether use of video laryngoscopy (VL) provided better NTI characteristics as compared to direct laryngoscopy (DL) in patients undergoing oromaxillofacial surgeries. Methods: We performed a systematic search to identify randomized controlled trials comparing VL with DL for NTI in adults undergoing elective oromaxillofacial surgery. The primary outcome was time to intubation. Secondary outcomes included the first attempt success, overall success, incidence of nasal bleeding, Cormack and Lehane grade, and maneuvers required. Results: Of the 456 studies identified following a systematic search, 10 were included. Meta-analysis showed a significantly lower time to tracheal intubation favoring VL (mean difference: -9.04, 95% CI [-12.71, -5.36], P < 0.001; I2 = 59%). VL was also associated with a greater first attempt success (relative risk [RR]: 1.10, 95% CI [1.04, 1.16], P = 0.001). Maneuvers to facilitate intubation were less with VL (RR: 0.22, 95% CI [0.10, 0.51], P < 0.001). There was no difference in overall intubation success (RR: 1.04, 95% CI [0.98, 1.10], P = 0.17). The incidence of bleeding did not differ between the DL and VL groups (RR: 0.59, 95% CI [0.32, 1.08], P = 0.09). Conclusions: Evidence as per this meta-analysis suggests VL leads to a shorter time to NTI, a greater first attempt success rate, and reduced need for maneuvers when compared to DL. The present study supports use of VL as a first line device for NTI in oral-maxillofacial surgeries in experienced hands. [ABSTRACT FROM AUTHOR]

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., (© 2024. Society of Surgical Oncology.)

Breast cancer (BC) has emerged as the most common malignancy among females. The genomic profile of BC is diverse in nature and complex due to heterogeneity among various geographically different ethnic groups. The primary objective of this study was to carry out a comprehensive mutational analysis of Indian BC cases by performing whole exome sequencing. The cohort included patients with a median age of 48 years. TTN, TP53, MUC16, SYNE1, and OBSCN were the frequently altered genes found in our cohort. The PIK3CA and KLC3 genes are driver genes implicated in various cellular functions and cargo transportation through microtubules, respectively. Except for CCDC168 and PIK3CA, several gene pairings were found to be significantly linked with co-occurrence. Irrespective of their hormonal receptor status, RTK/RAS was observed with frequently altered signaling pathways. Further analysis of the mutational signature revealed that SBS13, SBS6, and SBS29 were mainly observed in our cohort. This study supplements the discovery of diagnostic biomarkers and provides new therapeutic options for the improved management of BC., (© 2024. The Author(s).)

Purpose: Incorporating adjuvant cyclin-dependent kinase (CDK) 4/6 inhibitors abemaciclib and ribociclib along with endocrine therapy has been shown to improve invasive disease-free survival (iDFS) for hormone receptor-positive (HR+) human epidermal receptor 2-negative (HER2-) early breast cancer (EBC). This study assesses the cost-effectiveness of this strategy, along with adjuvant aromatase inhibitors from an Indian perspective., Methods: A Markov chain model evaluated the cost-effectiveness of abemaciclib and ribociclib with letrozole compared with letrozole alone for HR+/HER2- EBC from a payer perspective in India. Key measures included lifetime quality-adjusted life-years (QALY), life-years (LY), and total costs. This study explores two scenarios for effectiveness: a best-case (BC) scenario, where the benefit of CDK4/6 inhibitors in improving iDFS lasts a lifetime, and a worst-case (WC) scenario, where benefits disappear after 5 years. Probabilistic sensitivity analyses (PSA) were used to account for simulation uncertainty., Results: In the BC scenario, abemaciclib added 2.17 QALY and 4.96 LY, incurring ₹2,317,957.7 ($27,756.65 in US dollars [USD]) in additional costs. However, the incremental cost-effectiveness ratio (ICER) for abemaciclib exceeded India's willingness-to-pay threshold in the BC and WC scenarios. In the BC scenario, ribociclib added 0.98 QALY and 2.58 LY with added costs of ₹1,711,504.32 ($20,494.6 USD). The ICER for ribociclib also surpassed India's threshold in both scenarios. PSA showed that neither drug was cost-effective at the current market prices in either BC/WC scenario. The cost of abemaciclib and ribociclib needs to be reduced by at least 78.61% and 87.19%, respectively, to be cost-effective in the BC scenario., Conclusion: The combination of adjuvant abemaciclib or ribociclib with letrozole is not cost-effective for HR+/HER2- EBC in India in either the BC or WC scenario.

Purpose: Hand-foot syndrome (HFS) is a dose-limiting side effect of capecitabine. Celecoxib prevents HFS by inhibiting cyclooxygenase-2 (COX-2) that is upregulated because of the underlying associated inflammation. However, systemic side effects of celecoxib have limited routine prescription. Topical diclofenac inhibits COX-2 locally with minimal risk of systemic adverse events. Therefore, we conducted this study to assess the efficacy of topical diclofenac in the prevention of capecitabine-induced HFS., Methods: In this single-site phase III randomized double-blind trial, we enrolled patients with breast or GI cancer who were planned to receive capecitabine-based treatment. Participants were randomly assigned in a 1:1 ratio to receive topical diclofenac or placebo gel for 12 weeks or until the development of HFS, whichever occurred earlier. The primary end point was the incidence of grade 2 or 3 HFS (Common Terminology Criteria for Adverse Events version 5), which was compared between the two groups using simple logistic regression., Results: In total, 264 patients were randomly assigned to receive topical diclofenac gel (n = 131) or placebo (n = 133). Grade 2 or 3 HFS was observed in 3.8% of participants in the diclofenac group compared with 15.0% in the placebo group (absolute difference, 11.2%; 95% CI, 4.3 to 18.1; P = .003). Grade 1-3 HFS was lower in the diclofenac group than in the placebo group (6.1% v 18.1%; absolute risk difference, 11.9%; 95% CI, 4.1 to 19.6). Capecitabine dose reductions because of HFS were less frequent in the diclofenac group (3.8%) than in the placebo group (13.5%; absolute risk difference, 9.7%; 95% CI, 3.0 to 16.4)., Conclusion: Topical diclofenac prevented HFS in patients receiving capecitabine. This trial supports the use of topical diclofenac to prevent capecitabine-associated HFS.

Background: Approximately 20%-25% of patients with metastatic castration-resistant prostate cancer (mCRPC) harbor a deleterious germline or somatic mutation in the homologous recombination repair (HRR) pathway genes, which is involved in the repair of double-stranded DNA damage. Half of these mutations are germline, while the remaining are exclusively somatic. While polyadenosine 5'diphosphoribose [poly (ADP-ribose)] polymerase inhibitors, such as olaparib and rucaparib, are effective in this subgroup, their widespread use is limited due to the associated high cost, especially in resource-constrained settings. Notably, platinum agents like carboplatin have exquisite sensitivity to cells with defective DNA repair machinery. Carboplatin, a conventional, inexpensive chemotherapeutic agent, offers a potential alternative treatment in such patients. Several retrospective small case series support this hypothesis. However, there are no prospective clinical trials of carboplatin in patients with mCRPC with HRR mutations., Objective: The primary objective is to assess the objective response rate of 3 weekly carboplatin treatments in patients with mCRPC harboring deleterious mutations in the HRR pathway genes and previously treated with a taxane or a novel antiandrogen agent. The secondary objectives include progression-free survival, health-related quality of life, and safety profile of carboplatin., Methods: Patients diagnosed with mCRPC harboring HRR pathway mutations previously treated with docetaxel or novel antiandrogen agents (abiraterone, enzalutamide, apalutamide, or darolutamide) or both will be eligible. Genes involved directly or indirectly in the HRR pathway will be tested. In this single-arm phase II study, we will screen approximately 200 patients to enroll 49 patients, and carboplatin (dosing at the area under curve=5) will be administered every 3 weeks until progression or intolerable side effects. The primary end point will be assessed as the proportion of patients with a reduction of serum prostate-specific antigen by more than 50% from enrollment. Secondary outcomes include progression-free survival-soft-tissue disease progression (by response evaluation criteria in solid tumors, version 1.1, and bone lesion progression using Prostate Cancer Clinical Trials Working Group 3 criteria), health-related quality of life during carboplatin treatment using the Functional Assessment of Cancer Therapy-Prostate questionnaire and the European Organisation for Research and Treatment of Cancer questionnaire and safety profile of carboplatin (National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0)., Results: The trial started enrollment in September 2023. This trial is ongoing, and 12 patients have been recruited to date. All 49 participants will be enrolled according to plan., Conclusions: This prospective phase II trial represents a critical step toward addressing the therapeutic gap in patients with mCRPC harboring HRR pathway mutations, particularly in demographic regions with limited access to poly (ADP-ribose) polymerase inhibitors. Outcomes from this study will inform clinical practice and guide future phase III randomized trials, ultimately improving patient outcomes globally., Trial Registration: Clinical Trials Registry of India CTRI/2023/04/051507; https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=Njc0NjU=&Enc=&userName=., International Registered Report Identifier (irrid): DERR1-10.2196/54086., (©Rishabh Jain, Akash Kumar, Atul Sharma, Ranjit Kumar Sahoo, Aparna Sharma, Amlesh Seth, Brusabhanu Nayak, Shamim A Shamim, Seema Kaushal, Haresh KP, Chandan J Das, Atul Batra. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 18.04.2024.)

Purpose: Serial patient-reported outcome (PRO) measurements in clinical practice are associated with a better quality of life and survival. Recording electronic PROs using smartphones is an efficient way to implement this. We aimed to assess the feasibility of the electronically filled Edmonton Symptom Assessment System (e-ESAS) scale in the lower-middle-income country (LMIC) setting., Methods: Baseline clinical features and conventional paper-based ESAS (p-ESAS) were collected in newly diagnosed patients with solid organ tumors. Text message link was sent to these patients for filling e-ESAS. ESAS was categorized into physical, psychological, and total symptom domains. Scores were divided into none to mild (0-3) and moderate to severe (4-10). Intraclass correlation coefficients (ICCs) were used to determine the correlation between p-ESAS and e-ESAS. Multivariable logistic regression was used to identify independent factors affecting symptom burden., Results: Of 1,160 participants who filled out p-ESAS, 595 completed both e-ESAS and p-ESAS questionnaires and were included in the final analysis. Moderate to severe physical, psychological, and total symptom scores were seen in 39.8%, 40%, and 39% of participants. Tiredness and anxiety were the most common physical and psychological symptoms, respectively. ICCs between the p-ESAS and e-ESAS varied between 0.75 and 0.9. Total symptom scores were independently predicted by metastatic disease (odds ratio [OR], 1.83; 95% CI, 1.26 to 2.67; P = .001) and a higher level of education (OR, 0.42; 95% CI, 0.25 to 0.72; P = .001)., Conclusion: Paper-based and electronically filled ESASs have good intraobserver reliability across individual symptoms and domain scores in a representative cohort at a tertiary care institute in the LMIC. This may help us incorporate e-ESAS in routine clinical care in the real-world setting with financial, infrastructural, and manpower limitations.

Objectives: Dexamethasone sparing strategies have shown success. The feasibility of a dexamethasone-free antiemetic strategy remains undetermined. A prospective, single-arm, pilot study was planned to determine the efficacy of an olanzapine-based, dexamethasone-free, three-drug antiemetic regimen., Methods: Chemotherapy naïve, adult patients (≥18 years) who received ondansetron, aprepitant and olanzapine during the first cycle of highly emetogenic chemotherapy were enrolled. The primary endpoint was the rate of complete response (CR: no vomiting and no use of rescue medications) during the overall period (0-120 hours)., Results: Out of the total of 101 patients enrolled, most were women (82%) and received anthracycline cyclophosphamide (73%) combination therapy. The rate of CR for the overall period was 65% (95% CI 55.2% to 74.5%). The rate of CR for the acute and delayed period was 79% (95% CI 70% to 86.7%) and 76% (95% CI 66.7% to 84.1%). The rate of nausea control rates for the acute, delayed and overall periods were 34%, 29% and 24%, respectively. The grade I, II and III sedation rates over the 5 days were 8%, 5% and 1%, respectively., Conclusions: The dexamethasone-free antiemetic strategy showed modest efficacy with low incidence of clinically significant somnolence. There is a need to prospectively investigate the role of dexamethasone in the era of newer potent antiemetics in a randomised fashion., Trial Registration Number: CTRI/2021/07/034813., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2023 Wiley Periodicals LLC.)

Purpose: Patients with Germ cell tumours (GCT) are at risk of long-term toxicities due to multimodality therapy. It is debatable whether there is an impact on the quality of life(QoL) of GCT survivors., Methods: A case-control study was conducted at a tertiary care centre in India, using the EORTC QLQ C30 questionnaire, to compare the QoL between GCT survivors(disease free > 2 years) and healthy matched controls. A multivariate regression model was used to identify factors affecting QoL., Results: A total of 55 cases and 100 controls were recruited. Cases had a median age of 32 years (interquartile range, IQR 28-40 years), ECOG PS of 0-1(75%), advanced stage III (58%), chemotherapy (94%) and 66% were > 5 years from diagnosis. The median age of controls: 35 years (IQR 28-43 years). A statistically significant difference was seen for emotional (85.8 ± 14.2 vs 91.7 ± 10.4, p 0.005), social(83.0 ± 22.0 vs 95.2 ± 9.6, p < 0.001) and global scales (80.4 ± 21.1 vs 91.3 ± 9.7, p < 0.001). Cases had more nausea and vomiting(3.3 ± 7.4 vs 1.0 ± 3.9, p 0.015), pain(13.9 ± 13.9 vs 4.8 ± 9.8, p < 0.001), dyspnea(7.9 + 14.3 vs 2.7 ± 9.1, p 0.007), and appetite loss(6.7 ± 14.9 vs 1.9 ± 7.9, p 0.016) and greater financial toxicity(31.5 ± 32.3 vs 9.0 ± 16.3, p < 0.001). Adjusting for age, performance status, BMI, stage, chemotherapy, RPLND, recurrent disease, and time since diagnosis, no predictive variables were significant., Conclusion: There is a detrimental impact of history of GCT in long term survivors of GCT., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A woman in her 20s presented with headache and back pain and was found to have a left renal mass with bony metastases. She underwent nephrectomy, and on histopathology was initially diagnosed with stage 4 clear cell sarcoma of the kidney. She underwent palliative radiation and chemotherapy; however, the disease progressed and she came to our centre. We started her on second-line chemotherapy and submitted her tissue blocks for review. Due to her age and lack of sclerotic stroma in the tissue, we had our doubts about the diagnosis and hence, tissue sample was submitted for next-generation sequencing (NGS). NGS detected an EWSR1::CREBL1 fusion, clinching the final diagnosis of sclerosing epithelioid fibrosarcoma of the kidney, a singular diagnosis rarely reported in the literature. Currently, the patient is post her third line of chemotherapy, is on maintenance, and is doing well and has resumed her daily activities., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Abstract: Renal cell carcinoma (RCC) accounts for ~2% of global cancers and deaths. Survival depends on initial staging and shows poor survival rate in metastatic disease. CT and MRI are used for evaluating RCC, and PET/CT is used for metastatic disease assessment. We report a case of RCC, where both 18F-FDG and 68Ga-PSMA PET/CT showed increased uptake in liver metastatic lesions; however, a subhepatic peritoneal deposit showed uptake only in PSMA. Also, liver lesions were seen better in PSMA owing to lesser background uptake, suggesting a possibility of 68Ga-PSMA being a potential tracer for RCC evaluation., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Epithelial-to-mesenchymal transition (EMT) confers the most lethal characteristics to cancer cells i.e., metastasis and resistance to chemo-and-radio-therapy, and therefore exhibit an appealing target in the field of oncology. Research in the past decade has demonstrated the crucial role of aerobic glycolysis in EMT, which is generally credited as the glucose metabolism for the creation of biomass such as fatty acids, amino acids, and nucleotides thereby providing building blocks for limitless proliferation. In the present review, apart from discussing EMT's evident role in the metastatic process and cancer stemness, we also talked about the vital role of glycolytic enzymes viz. GLUTs, HKs, PGI, PFK-1, aldolase, enolase, PK, LDHA, etc. in the induction of the EMT process in cancerous cells., (© 2022. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Importance: Carboplatin increases the pathological complete remission (pCR) rate in triple negative breast cancer (TNBC) when added to neoadjuvant chemotherapy, however, evidence on its effect on survival outcomes is controversial., Methods: The study was prospectively registered at PROSPERO (CRD42021228386). We systematically searched PubMed, Embase, Cochrane Central Register of Clinical Trials, and conference proceedings from January 1, 2004 to January 30, 2022 for relevant randomized clinical trials (RCTs) of (neo)adjuvant chemotherapy in TNBC patients, with carboplatin in the intervention arm and standard anthracycline taxane (AT) in the control arm. PRISMA guidelines were used for this review. Data were pooled using fixed and random effects models as appropriate on extracted hazard ratios (HR). Individual patient data (IPD)for disease free survival (DFS) and overall survival (OS) were extracted from published survival curves of included RCTs; DFS and OS curves for each trial and the combined population were reconstructed, and HR estimated. The primary outcome was DFS; OS, pCR, and toxicity were secondary outcomes., Results: Eight trials with 2425 patients were included. Carboplatin improved DFS (HR 0.60; 95% CI 0.47 to 0.78; I 2 45%, p < 0.001) compared with AT at trial level and IPD level (HR 0.66; 95%CI, 0.55 to 0.80, p < 0.001) analysis. The OS also improved with carboplatin at both trial level (HR 0.69, 95%CI 0.50 to 0.95, I 2 41%, p = 0.02) and IPD level (HR 0.68; 95%CI, 0.54 to 0.87, p = 0.002) analysis. The pCR as expected, was better in the carboplatin arm (OR 2.11; 95% CI = 1.44-3.08; I 2 67%, p = 0.009). Anaemia and thrombocytopaenia were higher in the carboplatin arm., Conclusion: and relevance: Carboplatin added to (neo)adjuvant chemotherapy in TNBC improves survival, as shown in both trial level and IPD analysis., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Early detection of metastatic breast cancer (MBC) is a serious issue for the healthcare system. It is essential to develop potential non-invasive, low-cost molecular biomarkers. The present study explored specific serum proteins of inflammatory, MAPK, and cytoskeletal signaling pathways involved in the progression of MBC to establish a panel of blood-based diagnostic and prognostic biomarkers. Healthy-control (HC), non-metastatic (NM), and metastatic (M) (pre- and post-therapy) breast cancer (BC) patients were recruited. LOX5, Rac1, Rac1b, p38α, phospho-p38α (Y182), LIMK1, phospho-LIMK1 (T508), cofilin1, and phospho-cofilin1 (S3) were quantified in the serum of the study group by real-time label-free surface plasmon resonance technology and verified by Western blot. Proteins were found to be significantly elevated in the serum of BC patients compared to HC and also higher in M compared to NM, which further downregulated in post-therapy M patients. Elevation of phospho-LIMK1 and phospho-cofilin1, which are critical for M, was also indicated in the serum level and can differentiate from NM. Receiver operating characteristics (ROC) derived area under the curve (AUC) (0.9) is very strong to differentiate between HC and BC. Moreover, the combined ROC of 3 molecules phospho-LIMK, p38α, and phospho-p38α were found to be a potent predictive panel of biomarkers between M and NM with AUC0.95. The panel of inflammatory cytoskeleton signaling regime proteins specified in this study can have significant clinical utility for diagnosis as well as prognosis of MBC at an early stage. The study may have a high translational value in a simple and cost-effective way by avoiding frequent CT/PET scans., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Singh, Batra, Upadhaya, Gupta, K P and Dey.)

Purpose: This study aimed to determine the real-world prognostic significance of lymph node ratio (LNR) and log odds of positive lymph nodes (LOPLN) in patients with non-metastatic small bowel adenocarcinoma., Methods: Patients diagnosed with early-stage small bowel adenocarcinoma between January 2007 and December 2018 from a large Canadian province were identified. We calculated the LNR by dividing positive over total lymph nodes examined and the LOPLN as log ([positive lymph nodes + 0.5]/[negative lymph nodes + 0.5]). The LNR and LOPLN were categorized at cut-offs of 0.4 and -1.1, respectively. Multivariable Cox proportional hazards models were constructed for each nodal stage, LNR and LOPLN, adjusting for measured confounding factors. Harrell's C-index and Akaike's Information Criterion (AIC) were used to calculate the prognostic discriminatory abilities of the different models., Results: We identified 141 patients. The median age was 67 years and 54.6% were men. The 5-year overall survival rates for patients with stage I, II and III small bowel adenocarcinoma were 50.0%, 56.6% and 47.5%, respectively. The discriminatory ability was generally comparable for LOPLN, LNR and nodal stage in the prognostication of all patients. However, LOPLN had higher discriminatory ability among patients with at least one lymph node involvement (Harrell's C-index, 0.75, 0.77 and 0.82, and AIC, 122.91, 119.68 and 110.69 for nodal stage, LNR and LOPLN, respectively)., Conclusion: The LOPLN may provide better prognostic information when compared to LNR and nodal stage in specific patients.

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., (© 2021. Society of Surgical Oncology.)

Objective: There are contradictory data on differential effect of docetaxel based on BMI in patients with breast and prostate cancer. We performed an exploratory analysis to determine if the benefit of docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC) is modified by BMI., Methods: We performed a post hoc analysis of the data retrieved from the ENTHUSE M1C study. BMI (kg/m 2 ) was categorized as: 18.5 to <25 as lean; 25 to <30 as overweight; and ≥30 as obese. Cox regression models were constructed to determine the impact of BMI on progression-free survival (PFS) and overall survival (OS)., Results: A total of 466 patients were eligible for the current analysis. The median PFS was 7.3, 7.7 and 8.4 months (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.81 to 1.06; P = 0.261) in lean, overweight and obese patients. The median OS was 16.6, 20.1 and 21.4 months (HR, 0.75; 95% CI, 0.63 to 0.89; P = 0.002) for lean, overweight and obese patients. After adjusting for baseline and tumor characteristics, there was no association of BMI with PFS (overweight, HR, 0.89; 95% CI, 0.71 to 1.13; P = 0.353; obese, HR, 0.86; 95% CI, 0.66 to 1.13; P = 0.277) while overweight (HR, 0.68; 95% CI, 0.51 to 0.89; P = 0.006) and obese (HR, 0.59; 95% CI, 0.41 to 0.83; P = 0.003) patients had significantly better OS compared with lean patients., Conclusions: There was no effect of BMI on PFS in patients with mCRPC receiving docetaxel. Interestingly, overweight and obese patients had a longer OS compared with lean patients, which is in contradiction to a recent study in breast cancer; and warrants further investigation., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The POLO (Pancreas Cancer Olaparib Ongoing) trial demonstrated improvement in progression-free survival (PFS) with olaparib maintenance in advanced pancreatic cancer (APC) patients with germline BRCA1/2 mutations who had disease control after 16 weeks of platinum-based first-line therapy. However, in the real-world, the first assessment is usually performed at 12 weeks. Therefore, this study aimed to identify the proportion of real-world patients with APC that have disease control at 12 weeks (DC12) after FOLFIRINOX, assess any associations of baseline variables with DC12, and to determine the effect of DC12 on PFS and overall survival (OS)., Methods: APC patients treated with first-line FOLFIRINOX from 2011 to 2018 in Alberta, Canada, were identified. We conducted an analysis of baseline characteristics to identify factors associated with DC12 and to compare the PFS and OS of patients with DC12 to those with earlier disease progression., Results: We identified 165 APC patients treated with FOLFIRINOX with unknown BRCA1/2 status, of which 56% were men, and the median age at diagnosis was 59 years (interquartile range, 38 to 75 y). Of these, 72 (44%) had DC12. Lower serum carbohydrate antigen 19.9 and normal serum albumin were associated with a higher likelihood of DC12. The PFS and OS of patients with DC12 was significantly higher than those with earlier progression (9.3 vs. 2.5 mo; hazard ratio, 0.22; 95% confidence interval, 0.15-0.32; P<0.001; 21.6 vs. 8.9 mo; hazard ratio, 0.35; 95% confidence interval, 0.25-0.49; P<0.0001)., Conclusion: Less than half of real-world patients treated with first-line FOLFIRINOX have DC12. Patients with APC who have higher carbohydrate antigen 19.9 and low albumin are less likely to have DC12. DC12 is significantly associated with longer PFS and OS., Competing Interests: W.Y.C. and P.A.T. were on the advisory board of AstraZeneca. A.B. declares no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Treatment strategies for metastatic non-small cell lung cancer (NSCLC) are evolving rapidly and can be highly variable. Real-world evidence of treatment patterns and outcomes can provide an understanding of our current practice and offer insights on ways to incorporate emerging therapies into our treatment paradigm. In this population-based study, we investigated treatments and outcomes of stage IV NSCLC patients from a large Canadian province., Methods: Patients diagnosed with de novo stage IV NSCLC from April 1, 2010 to March 31, 2015 were identified. Data for baseline characteristics, treatments, and outcomes were obtained from provincial data sources, including the cancer registry and electronic medical records. We classified systemic treatments as chemotherapy, targeted therapy (anti-epidermal growth factor receptor, and anti-anaplastic lymphoma kinase) and immunotherapy (checkpoint inhibitors) and characterized clinical outcomes by treatment type., Results: A total of 6438 patients were identified with NSCLC, of whom 3606 (56%) had de novo stage IV disease. The median age of diagnosis was 69 (range: 20 to 100) years and 52.4% were men. First-line palliative treatments included: chemotherapy in 19.5% (n=703), targeted agents in 5.7% (n=204), immunotherapy in 1% (n=1), radiotherapy in 6.8% (n=246), and best supportive care in 74.8% (n=2,698). Median overall survival (mOS) from diagnosis for the whole cohort was 3.8 months. Within subgroups, mOS was 18.0 months for targeted therapies, 9.4 months for chemotherapy, and 2.5 months for best supportive care. Only 1.0% of patients (n=34) received immunotherapy at any line., Conclusions: Survival benefit was dependent on type of treatment received, with significantly better mOS observed with the use of small-molecule targeted therapy against epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangements, as compared with best supportive care., Competing Interests: M.H. and R.N.W. are affiliated with AstraZeneca, which manufactures, distributes, or markets immunotherapy and targeted therapy that have obtained regulatory approval for the indication of advanced NSCLC (durvalumab, gefinitib, and osimertinib). W.Y.C. and D.Y. have indirectly received honoraria or grants from the manufacturers of the drugs investigated in this study. The remaining authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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.

Background: Use of fluoropyrimidine-based therapy in patients with metastatic colorectal cancer is associated with significant toxicities. This study aimed to assess the safety and efficacy of raltitrexed use in patients with metastatic colorectal cancer who developed significant toxicities after fluoropyrimidine-based treatment., Patients and Methods: We identified patients with metastatic colorectal cancer who were treated with raltitrexed-based systemic therapy after developing serious adverse events with fluoropyrimidine-based treatment in a large Canadian province from 2004 to 2018. Demographic, tumor, and treatment characteristics were retrieved from the electronic medical records. Progression-free and overall survival were assessed from the start of raltitrexed-based therapy., Results: A total of 86 patients were identified for the study. The median age was 66.5 years, and 58.1% of patients were men. The primary cancer site was right, left, and transverse colon in 38.4%, 27.9%, and 9.3%, respectively. The remaining 24.4% had rectal cancer. Among all patients, 43.0% had received more than 2 prior systemic therapies, and 37.6% had developed previous cardiotoxicity to fluoropyrimidine-based treatment. The median progression-free and overall survival were 8.5 and 10.2 months, respectively. On multivariable Cox regression model, patients with left-sided colon cancer (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.12-0.97; P = .044) and the Eastern Cooperative Oncology Group performance status of 0/1 (HR, 0.10; 95% CI, 0.01-0.82; P = .032) had a longer progression-free survival, whereas left-sidedness of colon cancer was the only factor that predicted overall survival (HR, 0.30; 95% CI, 0.10-0.88; P = .029). Raltitrexed was well-tolerated with common adverse events that included anemia in 41.7% of patients and chemotherapy-induced nausea and vomiting in 27.4%. Most toxicities were grade 1/2, but 16.7% of patients experienced grade 3. There were no cardiac events and treatment-related deaths., Conclusions: Raltitrexed in patients with colorectal cancer who were previously treated with fluoropyrimidine-based systemic therapy is effective and well-tolerated., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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.

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.

Introduction: Patients with hormone receptor (HR)-positive, human epidermal growth factor receptor-2 (HER2)-negative, node negative (NN) breast cancer may be offered a gene expression profiling (GEP) test to determine recurrence risk and benefit of adjuvant chemotherapy. We developed a clinical-pathologic (CP) model to predict genomic recurrence risk and examined its performance characteristics., Methods: Patients diagnosed with HR-positive, HER2-negative, NN breast cancer with a tumour size < 30 mm and who underwent a GEP test [OncotypeDX or Prosigna] in Alberta from October 2017 through March 2019 were identified. Patients were classified as low or high genomic risk. Multivariable logistic regression analysis was performed to examine the associations of CP factors with genomic risk. A CP model was developed using coefficients of regression and sensitivity analyses were performed., Results: A total of 366 patients were eligible (135 were tested using OncotypeDX and 231 with Prosigna). Of these, 64 (17.5%) patients were classified as high genomic risk. On multivariable logistic regression, tumour size > 20 mm (odds ratio [OR], 3.58; 95% confidence interval [CI], 1.84-6.98; P<0.001), low expression of progesterone receptor (OR, 3.46; 95% CI, 1.76-6.82; P<0.001), and histological grade III (OR, 7.24; 95% CI, 3.82-13.70; P<0.001) predicted high genomic risk. A CP model using these variables was developed to provide a score of 0-4. A CP cut-point of 0, identified 56% of genomic low risk patients with a specificity of 98.4%., Conclusions: A CP model could be used to narrow the population of breast cancer patients undergoing GEP testing., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (Copyright © 2020 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Introduction: The results of adjuvant chemotherapy trials in stage II and III colon cancer are often extrapolated to real-world patients. This study was conducted to determine the proportion of real-world patients with stage II/III colon cancer who would be eligible for adjuvant chemotherapy trials and to compare the outcomes among eligible versus ineligible patients., Patients and Methods: We identified all patients diagnosed with stage II/III colon cancer between 2004 and 2015 from a large province in Canada. Patients meeting any one of the following criteria were considered ineligible: age > 75 years, anemia, comorbid conditions (heart disease, uncontrolled diabetes, kidney disease, liver disease), and a history of malignancy or immunosuppression. Cox regression models were constructed to determine the factors predicting overall and cancer-specific survival., Results: A total of 7841 patients with stage II/III colon cancer were identified, of whom 52.0% were men and median age at diagnosis was 71 years. Approximately 58.6% of patients were deemed trial ineligible; the most common reasons for ineligibility included advanced age (36.2%), renal dysfunction (26.9%), and cardiac disease (17.4%). In the real-world setting, 54.0% of eligible patients received adjuvant chemotherapy compared to 23.2% of ineligible patients (odds ratio, 3.89; 95% confidence interval, 3.53-4.28; P < .0001). The 5-year overall and cancer-specific survival of trial-ineligible patients who received adjuvant chemotherapy was significantly better than those treated with surgery alone., Conclusion: The eligibility criteria of adjuvant chemotherapy trials in colon cancer should be broadened to be more representative of real-world patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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., (Copyright © 2020. Published by Elsevier Inc.)

Introduction: The results of clinical trials in metastatic breast cancer (MBC) are generalized to real-world patients. This study determines the proportion of real-world patients who would be eligible for clinical trials and compares outcomes in eligible versus ineligible patients., Methods: Patients diagnosed with MBC from 2004 to 2015 in a large Canadian province were included. Patients with one of the following criteria were considered ineligible: the presence of comorbid conditions (anemia, uncontrolled diabetes, heart disease, liver disease, and kidney disease) or a history of immunosuppression or prior malignancy. The likelihood of receiving cancer therapy was analysed using logistic regression models and factors affecting overall survival (OS) were assessed by Cox proportional hazards models., Results: A total of 1585 patients with MBC were identified. The median age at diagnosis was 63 years. Of these, 512 (32.3%) patients were deemed ineligible in whom the two most common reasons for ineligibility were renal dysfunction (17.2%), and previous immunosuppression (7.8%). In the real world, ineligible patients were less likely to receive chemotherapy (29.5% vs 45.8%; P < 0.001) but not radiation treatment (7.6% vs 9.6%; P = 0.196) or hormonal therapy (57.6% vs 60.6%; P = 0.261). The 5-year OS of ineligible patients who received systemic therapy in the real-world was significantly better than those who did not., Conclusions: Despite being ineligible for clinical trials based on common eligibility criteria, many real-world patients receive systemic treatment and derive possible benefit. Broadening of inclusion criteria in clinical trials will enhance the representation of real-world patients and increase the generalizability of results., Competing Interests: Declaration of competing interest None declared., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The optimal number of cycles of adjuvant docetaxel and cyclophosphamide (DC) in patients with node negative breast cancer is not known. We aimed to analyse the survival outcomes of patients with node negative and human epidermal growth factor receptor (HER2)-negative breast cancer treated with four cycles of DC., Methods: Patients with node negative and HER2-negative breast cancer treated with four cycles of DC after surgery in a large Canadian province from 2008 to 2012 were identified. We analysed the 4-year and 9-year invasive disease free survival (iDFS) and overall survival (OS). Cox regression models were constructed to examine the associations of clinical characteristics with survival outcomes., Results: A total of 657 patients were eligible for the current analysis. The median age was 53 years and 71.2% of patients had hormone receptor-positive breast cancer. Approximately three-fourths of patients had grade III tumours. At a median follow-up of nine years, the 4-year iDFS and OS were 91.0% and 95.5% and the corresponding 9-year rates were 80.5% and 88.0%, respectively. On multivariable Cox regression analysis, grade III tumour predicted worse iDFS (hazard ratio [HR], 2.15; 95% confidence interval [CI], 1.09-4.21; P = 0.026) and OS (HR, 3.15; 95% CI, 1.18-8.45; P = 0.022)., Conclusions: Adjuvant chemotherapy with four cycles of DC in a select population of node negative breast cancer was associated with encouraging long-term survival. In the absence of a randomized comparison between four and six cycles of DC, this study presents real-world evidence to consider four cycles of DC as a reasonable option., Competing Interests: Declaration of competing interest None declared., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: We aimed to explore possible drivers for urban-rural disparities in colon cancer outcomes in a single-payer health care system where all patients had access to universal health care coverage., Methods: Patients diagnosed with stage II/III colon cancer between 2004 and 2015 in Alberta, Canada were reviewed. On the basis of postal code, patients were categorized as living in urban, rural, or suburban areas based on travel distance to the cancer center. Kaplan-Meier methods and Cox regression models assessed the associations among the area of residence, receipt of treatment, and overall survival (OS)., Results: Of 6163 patients identified, there were 3691, 1779, and 693 from urban, rural, and suburban areas, respectively. There was a larger proportion of younger patients (P=0.033) and left-sided colon cancers (P=0.042) in urban areas. Urban patients experienced shorter times from diagnosis to surgery (P<0.001), but longer delays from surgery to adjuvant chemotherapy (P=0.001). A significant difference in outcomes was identified among urban, rural, and suburban populations where median OS were 104, 94, and 83 months, respectively (P<0.001). In multivariate analysis, the location of residence continued to predict for worse OS in suburban (hazard ratio=1.60, 95% confidence interval: 1.24-2.07, P<0.001) and rural areas (hazard ratio=1.24, 95% confidence interval: 1.02-1.50, P=0.042), when compared with urban areas., Conclusions: In this population-based study, urban-rural differences in colon cancer survival persist, even in settings with universal health care coverage. These findings may be partly driven by a younger population with more left-sided colon cancers as well as expedited surgical intervention in urban populations, but these factors do not fully explain the disparities.

Competing Interests: None

Engraftment syndrome (ES) is a clinical syndrome that occurs in the early neutrophil recovery phase following hematopoietic stem cell transplant (HSCT). Although also described for allogenic HSCT, it is basically diagnosed in the context of autologous HSCT. We retrospectively reviewed 171 consecutive HSCTs performed between January 2013 and January 2015 in our Bone Marrow Transplant (BMT) unit and analyzed all cases of noninfectious fever and strong clinical features suggestive of ES in the peri-engraftment period for up to 7 days. We observed the incidence of ES to be 12.3% (16/130) in the autologous and 4.8% (2/41) in the allogeneic cohort. Among plasma cell disorders, which constitute 50% of our study population, the incidence of ES was 19.7%. Among the ES cases of autologous transplants, 81.2% (13/16) patients satisfied the Maiolino criteria (MC) and 87.5% (14/16) patients the Spitzer diagnostic criteria (SC). A total of 68.7% (11/16) patients satisfied both MC and SC, and two patients (12.5%) did not satisfy either (MC- SC-). There was no significant difference in days of hospitalization and usage of supportive care between ES and non-ES patients, and there was no mortality due to ES. On univariate analysis, female patients (p < 0.013) and those with diagnosis of a plasma cell disorder (p < 0.03) had higher risk of ES. In conclusion, the incidence of ES in our study population is consistent with that of many others, but severity evaluation needs exploration in larger cohorts with pragmatically modified diagnostic criteria., Competing Interests: Authors declare no conflict of interests for this article., (© 2019 International Academy for Clinical Hematology. Publishing services by Atlantis Press International B.V.)

Primary yolk sac tumor of the liver is extremely rare in adults. We report a case of a young man with an unresectable primary yolk sac tumor of the liver, who had a platinum-refractory disease that progressed despite 2 lines of chemotherapy. We review the literature pertaining to primary yolk sac tumor of the liver and its management., (© 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Importance: Although oral metronomic chemotherapy is often used in progressive pediatric solid malignant tumors, a literature review reveals that only small single-arm retrospective or phase 1 and 2 studies have been performed. Skepticism abounds because of the lack of level 1 evidence., Objectives: To compare the effect of metronomic chemotherapy on progression-free survival (PFS) with that of placebo in pediatric patients with primary extracranial, nonhematopoietic solid malignant tumors that progress after at least 2 lines of chemotherapy., Design, Setting, and Participants: A double-blinded, placebo-controlled randomized clinical trial was conducted from October 1, 2013, through December 31, 2015, at the cancer center at All India Institute of Medical Sciences in children aged 5 to 18 years with primary extracranial, nonhematopoietic solid malignant tumors that progressed after at least 2 lines of chemotherapy and had no further curative options., Interventions: One arm received a 4-drug oral metronomic regimen of daily celecoxib and thalidomide with alternating periods of etoposide and cyclophosphamide, whereas the other arm received placebo. Disease status was assessed at baseline, 9 weeks, 18 weeks, and 27 weeks or at clinical progression., Main Outcomes and Measures: The primary end point was PFS as defined by the proportion of patients without disease progression at 6 months, and PFS duration and overall survival (OS) were secondary end points., Results: A total of 108 of the 123 patients screened were enrolled, with 52 randomized to the placebo group (median age, 15 years; 40 male [76.9%]) and 56 to the metronomic chemotherapy group (median age, 13 years; 42 male [75.0%]). At a median follow-up of 2.9 months, 100% of the patients had disease progression by 6 months in the placebo group vs 96.4% in the metronomic chemotherapy group (P = .24). Median PFS and OS in the 2 groups was similar (hazard ratio [HR], 0.69; 95% CI, 0.47-1.03 [P = .07] for PFS; and HR, 0.74; 95% CI, 0.50-1.09 [P = .13] for OS). In post hoc subgroup analysis, cohorts receiving more than 3 cycles (HR for PFS, 0.46; 95% CI, 0.23-0.93; P = .03) and those without a bone sarcoma (ie, neither primitive neuroectodermal tumor nor osteosarcoma) (HR for PFS, 0.39; 95% CI, 0.18-0.81; P = .01) appeared to benefit from metronomic chemotherapy., Conclusions and Relevance: Metronomic chemotherapy does not improve 6-month PFS, compared with placebo, among pediatric patients with extracranial progressive solid malignant tumors . However, patients without bone sarcoma and those able to tolerate therapy for more than 3 cycles (9 weeks) benefit., Trial Registration: clinicaltrials.gov Identifier: NCT01858571.