Search

ObjectivesDexamethasone 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.MethodsChemotherapy nai¨ve, 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).ResultsOut 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.ConclusionsThe 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 numberCTRI/2021/07/034813.

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.

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.

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.

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.

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.

Forkhead box (FOX) transcription factors are a class of highly conserved proteins, which serve critical cellular functions including cell cycle regulation. The downstream mechanisms of cell cycle regulation involve preservation of retinoblastoma protein function. Its deactivation by phosphorylation and translocation from nucleus to cytoplasm leads to cell proliferation. FOXO3a has been found to be dysregulated in few cancers. However, no study has been reported on role of FOXO3a in retinoblastoma. We assessed the expression of FOXO3a in sections of archived tissue blocks of enucleated/exenterated specimens of retinoblastoma by immunohistochemistry. The histopathologic features were reviewed and correlated with its expression. Effect of FOXO3a expression on survival was assessed. FOXO3a expression was assessed in 100 sections. Six samples did not contain any viable tissue. Retrospective data of 94 patients revealed that median age at presentation was 36 months with male:female ratio of 1.9:1. Fifty-one percent of patients were International Retinoblastoma Staging System stage 1. Of the 94 sections, 68 (72%) showed cytoplasmic expression. Choroidal invasion was associated with cytoplasmic FOXO3a (P=0.04). A trend was also noted in optic nerve cut end involvement (P=0.07). No other histopathologic features were found to be associated with FOXO3a expression. The overall survival and progression-free survival were not found to be affected by FOXO3a expression. Cytoplasmic expression of FOXO3a is frequently found in retinoblastoma and may be involved in pathogenesis. Activation by relocation of FOXO3a to nucleus may activate nonmutated retinoblastoma and may be a potential target of treatment in retinoblastoma.

Background:Sirtuin1 (Sirt1) is a member of highly conserved proteins and has been implicated as a tumor promoter as well as a tumor suppressor. One of the mechanisms involves deacetylation of retinoblastoma protein, thereby inhibiting the tumor suppressor function. No study has been reported on the expression of Sirt1 in retinoblastoma. Methods:We assessed the expression of Sirt1 in sections of archived tissue blocks of enucleated and exenterated specimens of retinoblastoma patients by immunohistochemistry. The histopathological features were reviewed and correlated with the expression of Sirt1. The effect of Sirt1 expression on survival was also assessed. Results:Retrospective data of 94 patients revealed that the median age at presentation was 36 months, with a male:female ratio of 1.9:1. Fifty-one percent of the patients had International Retinoblastoma Staging System (IRSS) stage 1 disease. Of the 94 sections, 89 (95%) expressed Sirt1. Forty-eight percent of the specimens showed grade 3 staining (>75% of the cells), and the intensity was 3+ in 53%. No association between Sirt1 expression and any histopathological feature was noted. Further, Sirt1 expression did not affect the overall and progression-free survival. Conclusions:Sirt1 was expressed in most of the retinoblastoma samples. However, the degree of Sirt1 expression was not associated with any high-risk histopathological feature or survival.

IMPORTANCE: Several real-world oncology studies have produced findings that contradict those from randomized clinical trials. Such disparities may be associated with methodological shortcomings. OBJECTIVE: To examine the association between a shortened duration of adjuvant chemotherapy among individuals with stage III colon cancer using real-world data. DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness study included individuals diagnosed with stage III colon cancer between January 2004 and December 2015 who initiated adjuvant chemotherapy at oncology clinics within the province of Alberta, Canada. Patients were identified through record linkage of various administrative databases and were followed up until September 2017. Eligibility criteria were modeled after those used in the International Duration Evaluation of Adjuvant (IDEA) trial. A target trial emulation and naive observational analysis were conducted. Results from both cohorts were benchmarked against findings from the IDEA trial. Data analysis was conducted from March to December 2020. EXPOSURE: A shortened duration of adjuvant 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX) or capecitabine plus oxaliplatin (CAPOX) chemotherapy, defined as 3 to 5 months of treatment vs 6 months. MAIN OUTCOMES AND MEASURES: Overall survival assessed via vital statistics. The per-protocol hazard ratio (HR) was estimated using a weighted pooled logistic regression model. Subgroup analyses were conducted by treatment regimen (ie, FOLFOX vs CAPOX) and cancer stage (ie, T1-3 and N1 vs T4 or N2). RESULTS: From an initial cohort of 3086 patients, 485 (16%) were eligible for inclusion in the target trial analysis. The median age was 59 years (range, 19-81 years), and 230 (47%) were women. The maximum follow-up was 11.6 years. Median overall survival was not reached. A total of 90 patients (19%) died. The 5-year Kaplan Meier overall survival estimate was 0.79 (95% CI, 0.75-0.84). Estimates from the trial emulation were similar to those from the IDEA trial. For example, a shortened duration of adjuvant chemotherapy was not associated with overall survival among patients prescribed CAPOX in the IDEA trial (HR, 0.96; 95% CI, 0.85-1.08) or in the trial emulation (HR, 0.96; 95% CI, 0.43-2.14). In contrast, the naive observational analysis suggested that a shortened duration of CAPOX was significantly associated with worse survival (HR, 3.33; 95% CI, 1.04-10.65). CONCLUSIONS AND RELEVANCE: In this study, the explicit emulation of a target trial better approximated results from an analogous well-conducted randomized clinical trial.