Explore the vast range of titles available.

Introduction Although there have been reports of chemotherapy-induced nausea and vomiting (CINV) beyond 120 h, its overall prevalence has not been systematically examined. The aim of this review and meta-analysis was to report on the prevalence of this long-delayed CINV. Methods This review was registered on PROSPERO (CRD42022346963). PubMed (Medline), Embase, and Cochrane Central were searched from inception until August 2022. Articles were included if they reported on CINV > 120 h after initiation of the chemotherapy regimen and patients received a single-agent highly emetogenic (HEC) or moderately emetogenic (MEC) antineoplastic agent for 1 day alone or in combination with low/minimal emetogenic chemotherapy. For all eligible articles, individual study authors were contacted and requested to provide individual patient-level data of demographics, emetogenicity of chemotherapy regimens, and daily incidence of nausea and vomiting. Forward stepwise logistic regression identified predictors for the incident day’s CINV based on prior day’s CINV episodes, controlling for patient demographics, and stratified by regimen emetogenicity. Results A total of 2048 patients from 2 studies were included in this individual patient data meta-analysis: 1333 patients (65%) received HEC and 715 (35%) received MEC. Among those receiving HEC, 325 (24%) experienced acute, 652 (49%) delayed, and 393 (31%) long-delayed nausea; 107 (8%) experienced acute, 179 (14%) delayed, and 79 (6%) long-delayed vomiting. Among those receiving MEC, 48 (7%) experienced acute, 272 (38%) delayed, and 167 (24%) long-delayed nausea; 12 (2%) experienced acute, 97 (14%) delayed, and 42 (6%) long-delayed vomiting. Nausea in the long-delayed phase was as severe as in the delayed phase. Patients experiencing nausea and vomiting on days 4 and 5 were at significant risk of experiencing long-delayed CINV. Conclusion While not as prevalent as delayed nausea and vomiting, long-delayed CINV affects a significant proportion of patients and severity is similar. Patients with delayed CINV, specifically on days 4–5, are at risk of experiencing long-delayed CINV.

Purpose Female patients with breast cancer frequently develop arthralgia when treated with aromatase inhibitors (AI). Although the mechanism of AI-induced arthralgia is unknown, potential biomarkers have been identified. The purpose of this study was to investigate the clinical and genetic predictors of AI-induced arthralgia in a prospective cohort of patients with estrogen receptor-positive breast cancer. Methods One hundred and ninety-six patients were enrolled at initiation of AI therapy with either letrozole or anastrozole. Patients completed two validated self-report questionnaires assessing pain, stiffness, and physical function at baseline, and repeated the questionnaires at two and at six months after the initiation of treatment with an AI. Germline DNA of all patients was genotyped for seven single-nucleotide polymorphisms (SNPs) previously identified by genetic screens and genome-wide association studies as associated with AI-induced arthralgia. Results More than 50% of the study group experienced arthralgia symptoms. Genetic analysis revealed that four SNPs, in CYP19A1 (rs4775936) and ESR1 (rs9322336, rs2234693, rs9340799), were associated with the development of arthralgia (adjusted P  = 0.016, 0.018, 0.017, 0.047). High body mass index (BMI) was also associated with the development of arthralgia symptoms (adjusted P  = 0.001). Patients prescribed letrozole were significantly more likely to develop arthralgia than patients on anastrozole ( P  = 0.018), and also more likely to discontinue AI therapy due to arthralgia. The CYP19A1 (rs4775936) SNP was significantly associated with discontinuation of therapy due to intolerable arthralgia. Conclusions Our results suggested that BMI and AI drug (letrozole versus anastrozole) were clinical predictors of arthralgia, while genetic variants rs4775936, rs9322336, rs2234693, and rs9340799 were genetic predictors of AI-induced arthralgia. Significantly, rs4775936 was also a predictor of discontinuation of therapy.

Background Our aim was to establish if presence of circulating tumor cells (CTCs) predicted worse outcome in patients with non-metastatic esophageal cancer undergoing tri-modality therapy. Methods We prospectively collected CTC data from patients with operable non-metastatic esophageal cancer from April 2009 to November 2016 enrolled in our QUINTETT esophageal cancer randomized trial (NCT00907543). Patients were randomized to receive either neoadjuvant cisplatin and 5-fluorouracil (5-FU) plus radiotherapy followed by surgical resection (Neoadjuvant) or adjuvant cisplatin, 5-FU, and epirubicin chemotherapy with concurrent extended volume radiotherapy following surgical resection (Adjuvant). CTCs were identified with the CellSearch® system before the initiation of any treatment (surgery or chemoradiotherapy) as well as at 6-, 12-, and 24-months post-treatment. The threshold for CTC positivity was one and the findings were correlated with patient prognosis. Results CTC data were available for 74 of 96 patients and identified in 27 patients (36.5%) at a median follow-up of 13.1months (interquartile range:6.8-24.1 months). Detection of CTCs at any follow-up visit was significantly predictive of worse disease-free survival (DFS;hazard ratio [HR]: 2.44; 95% confidence interval [CI]: 1.41-4.24; p =0.002), regional control (HR: 6.18; 95% CI: 1.18-32.35; p =0.031), distant control (HR: 2.93; 95% CI: 1.52-5.65; p =0.001) and overall survival (OS;HR: 2.02; 95% CI: 1.16-3.51; p =0.013). After adjusting for receiving neoadjuvant vs. adjuvant chemoradiotherapy, the presence of CTCs at any follow-up visit remained significantly predictive of worse OS ([HR]:2.02;95% [Cl]:1.16-3.51; p =0.013) and DFS (HR: 2.49;95% Cl: 1.43-4.33; p =0.001). Similarly, any observed increase in CTCs was significantly predictive of worse OS (HR: 3.14; 95% CI: 1.56-6.34; p =0.001) and DFS (HR: 3.34; 95% CI: 1.67-6.69; p <0.001). Conclusion The presence of CTCs in patients during follow-up after tri-modality therapy was associated with significantly poorer DFS and OS regardless of timing of chemoradiotherapy.

Background We compared the health‐related quality of life (HRQOL) in patients undergoing trimodality therapy for resectable stage I‐III esophageal cancer. Methods A total of 96 patients were randomized to standard neoadjuvant cisplatin and 5‐fluorouracil chemotherapy plus radiotherapy (neoadjuvant) followed by surgical resection or adjuvant cisplatin, 5‐fluorouracil, and epirubicin chemotherapy with concurrent extended volume radiotherapy (adjuvant) following surgical resection. Results There was no significant difference in the functional assessment of cancer therapy‐esophageal (FACT‐E) total scores between arms at 1 year (p = 0.759) with 36% versus 41% (neoadjuvant vs. adjuvant), respectively, showing an increase of ≥15 points compared to pre‐treatment (p = 0.638). The HRQOL was significantly inferior at 2 months in the neoadjuvant arm for FACT‐E, European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ‐OG25), and EuroQol 5‐D‐3 L in the dysphagia, reflux, pain, taste, and coughing domains (p < 0.05). Half of patients were able to complete the prescribed neoadjuvant arm chemotherapy without modification compared to only 14% in the adjuvant arm (p < 0.001). Chemotherapy related adverse events of grade ≥2 occurred significantly more frequently in the neoadjuvant arm (100% vs. 69%, p < 0.001). Surgery related adverse events of grade ≥2 were similar in both arms (72% vs. 86%, p = 0.107). There were no 30‐day mortalities and 2% vs. 10% 90‐day mortalities (p = 0.204). There were no significant differences in either overall survival (OS) (5‐year: 35% vs. 32%, p = 0.409) or disease‐free survival (DFS) (5‐year: 31% vs. 30%, p = 0.710). Conclusion Trimodality therapy is challenging for patients with resectable esophageal cancer regardless of whether it is given before or after surgery. Newer and less toxic protocols are needed. This randomized trial assessed the health related quality of life in esophageal cancer patients undergoing neoadjuvant versus adjuvant trimodality therapy. Every patient experienced at least one adverse event. The quality of life was worse for patients undergoing neoadjuvant compared to adjuvant chemoradiation with no significant difference in either overall survival or disease‐free survival. More effective therapy is needed.

Introduction Although there have been reports of chemotherapy-induced nausea and vomiting (CINV) beyond 120 h, its overall prevalence has not been systematically examined. The aim of this review and meta-analysis was to report on the prevalence of this long-delayed CINV. Methods This review was registered on PROSPERO (CRD42022346963). PubMed (Medline), Embase, and Cochrane Central were searched from inception until August 2022. Articles were included if they reported on CINV > 120 h after initiation of the chemotherapy regimen and patients received a single-agent highly emetogenic (HEC) or moderately emetogenic (MEC) antineoplastic agent for 1 day alone or in combination with low/minimal emetogenic chemotherapy. For all eligible articles, individual study authors were contacted and requested to provide individual patient-level data of demographics, emetogenicity of chemotherapy regimens, and daily incidence of nausea and vomiting. Forward stepwise logistic regression identified predictors for the incident day's CINV based on prior day's CINV episodes, controlling for patient demographics, and stratified by regimen emetogenicity. Results A total of 2048 patients from 2 studies were included in this individual patient data meta-analysis: 1333 patients (65%) received HEC and 715 (35%) received MEC. Among those receiving HEC, 325 (24%) experienced acute, 652 (49%) delayed, and 393 (31%) long-delayed nausea; 107 (8%) experienced acute, 179 (14%) delayed, and 79 (6%) long-delayed vomiting. Among those receiving MEC, 48 (7%) experienced acute, 272 (38%) delayed, and 167 (24%) long-delayed nausea; 12 (2%) experienced acute, 97 (14%) delayed, and 42 (6%) long-delayed vomiting. Nausea in the long-delayed phase was as severe as in the delayed phase. Patients experiencing nausea and vomiting on days 4 and 5 were at significant risk of experiencing long-delayed CINV. Conclusion While not as prevalent as delayed nausea and vomiting, long-delayed CINV affects a significant proportion of patients and severity is similar. Patients with delayed CINV, specifically on days 4-5, are at risk of experiencing long-delayed CINV.

Although there have been reports of chemotherapy-induced nausea and vomiting (CINV) beyond 120 h, its overall prevalence has not been systematically examined. The aim of this review and meta-analysis was to report on the prevalence of this long-delayed CINV. This review was registered on PROSPERO (CRD42022346963). PubMed (Medline), Embase, and Cochrane Central were searched from inception until August 2022. Articles were included if they reported on CINV > 120 h after initiation of the chemotherapy regimen and patients received a single-agent highly emetogenic (HEC) or moderately emetogenic (MEC) antineoplastic agent for 1 day alone or in combination with low/minimal emetogenic chemotherapy. For all eligible articles, individual study authors were contacted and requested to provide individual patient-level data of demographics, emetogenicity of chemotherapy regimens, and daily incidence of nausea and vomiting. Forward stepwise logistic regression identified predictors for the incident day's CINV based on prior day's CINV episodes, controlling for patient demographics, and stratified by regimen emetogenicity. A total of 2048 patients from 2 studies were included in this individual patient data meta-analysis: 1333 patients (65%) received HEC and 715 (35%) received MEC. Among those receiving HEC, 325 (24%) experienced acute, 652 (49%) delayed, and 393 (31%) long-delayed nausea; 107 (8%) experienced acute, 179 (14%) delayed, and 79 (6%) long-delayed vomiting. Among those receiving MEC, 48 (7%) experienced acute, 272 (38%) delayed, and 167 (24%) long-delayed nausea; 12 (2%) experienced acute, 97 (14%) delayed, and 42 (6%) long-delayed vomiting. Nausea in the long-delayed phase was as severe as in the delayed phase. Patients experiencing nausea and vomiting on days 4 and 5 were at significant risk of experiencing long-delayed CINV. While not as prevalent as delayed nausea and vomiting, long-delayed CINV affects a significant proportion of patients and severity is similar. Patients with delayed CINV, specifically on days 4-5, are at risk of experiencing long-delayed CINV.

Neurofibromatosis type 1 (NF1) is an autosomal dominant neuroectodermal disorder associated with increased risk for several neural and non-neural malignancies. The link between NF1 and breast cancer has recently been established, with patients with NF1 being at higher risk for developing breast cancer, more likely to get breast cancer at a younger age, and more likely to have their breast cancer present with more adverse prognostic factors. Although rare, several cases of NF1 patients with contralateral breast cancer have been mentioned in the literature. We report the case of one such patient who developed contralateral breast cancer 40 years after her initial breast cancer diagnosis.

Tamoxifen is a widely utilized adjuvant anti-estrogen agent for hormone receptor-positive breast cancer, known to undergo CYP2D6-mediated bioactivation to endoxifen. However, little is known regarding additional genetic and non-genetic determinants of optimal endoxifen plasma concentration. Therefore, 196 breast cancer patients on tamoxifen were enrolled in this prospective study over a 24-month period. Blood samples were collected for pharmacogenetic and drug-level analysis of tamoxifen and metabolites. Regression analysis indicated that besides CYP2D6, the recently described CYP3A4 *22 genotype, seasonal variation, and concomitant use of CYP2D6-inhibiting antidepressants were significant predictors of endoxifen concentration. Of note, genetic variation explained 33 % of the variability while non-genetic variables accounted for 13 %. Given the proposed notion of a sub-therapeutic endoxifen concentration for predicting breast cancer recurrence, we set the therapeutic threshold at 18 nM, the 20th percentile for endoxifen level among enrolled patients in this cohort. Nearly 70 % of CYP2D6 poor metabolizers as well as extensive metabolizers on potent CYP2D6-inhibiting antidepressants exhibited endoxifen levels below 18 nM, while carriers of CYP3A4 *22 were twofold less likely to be in sub-therapeutic range. Unexpectedly, endoxifen levels were 20 % lower during winter months than mean levels across seasons, which was also associated with lower vitamin D levels. CYP3A4 *22 genotype along with sunshine exposure and vitamin D status may be unappreciated contributors of tamoxifen efficacy. The identified covariates along with demographic variables were integrated to create an endoxifen concentration prediction algorithm to pre-emptively evaluate the likelihood of individual patients falling below the optimal endoxifen concentration.

Background Although radiotherapy is a key component of curative-intent treatment for locally advanced, unresectable non-small cell lung cancer (NSCLC), it can be associated with substantial pulmonary toxicity in some patients. Current radiotherapy planning techniques aim to minimize the radiation dose to the lungs, without accounting for regional variations in lung function. Many patients, particularly smokers, can have substantial regional differences in pulmonary ventilation patterns, and it has been hypothesized that preferential avoidance of functional lung during radiotherapy may reduce toxicity. Although several investigators have shown that functional lung can be identified using advanced imaging techniques and/or demonstrated the feasibility and theoretical advantages of avoiding functional lung during radiotherapy, to our knowledge this premise has never been tested via a prospective randomized clinical trial. Methods/Design Eligible patients will have Stage III NSCLC with intent to receive concurrent chemoradiotherapy (CRT). Every patient will undergo a pre-treatment functional lung imaging study using hyperpolarized 3 He MRI in order to identify the spatial distribution of normally-ventilated lung. Before randomization, two clinically-approved radiotherapy plans will be devised for all patients on trial, termed standard and avoidance . The standard plan will be designed without reference to the functional state of the lung, while the avoidance plan will be optimized such that dose to functional lung is as low as reasonably achievable. Patients will then be randomized in a 1:1 ratio to receive either the standard or the avoidance plan, with both the physician and the patient blinded to the randomization results. This study aims to accrue a total of 64 patients within two years. The primary endpoint will be a pulmonary quality of life (QOL) assessment at 3 months post-treatment, measured using the functional assessment of cancer therapy–lung cancer subscale. Secondary endpoints include: pulmonary QOL at other time-points, provider-reported toxicity, overall survival, progression-free survival, and quality-adjusted survival. Discussion This randomized, double-blind trial will comprehensively assess the impact of functional lung avoidance on pulmonary toxicity and quality of life in patients receiving concurrent CRT for locally advanced NSCLC. Trial registration Clinicaltrials.gov identifier: NCT02002052 .

PurposeThe aromatase inhibitor (AI) letrozole is a first-line drug in the adjuvant treatment of breast cancer in postmenopausal women. Adherence to AI therapy, including letrozole, remains problematic due to the development of debilitating AI-induced arthralgia. Letrozole is metabolized in the liver by CYP2A6. It remains unknown if plasma letrozole levels or CYP2A6 genetic variation is associated with the development of arthralgia.MethodsWe enrolled 126 female breast cancer patients initiated on letrozole therapy and prospectively collected blood samples at baseline and two follow-up time points to determine letrozole plasma concentrations and CYP2A6 genotype. At each visit, participants completed two validated questionnaires to assess the severity of arthralgia symptoms.ResultsMore than half (55%) of patients experienced a significant increase in their arthralgia symptoms after initiation of treatment. The clinical variables of body mass index (P = 0.0003) and age (P = 0.0430) were negatively and positively associated with plasma letrozole concentrations, respectively. CYP2A6 genotype was significantly associated with letrozole levels (P < 0.0001), and increased plasma letrozole levels were observed in patients with CYP2A6 reduced-function genotypes. Plasma levels of letrozole and CYP2A6 genotype were not significantly associated with a change in pain score from baseline.ConclusionsCYP2A6 genotype was a significant predictor of letrozole plasma levels, but was not associated with the development of arthralgia.