Effects of food-based interventions in the management of chemoradiotherapy-induced nausea and vomiting: a systematic review.

BACKGROUND: Cancer treatment-related nausea and vomiting continue to be common and distressing symptoms for patients, despite improvements in antiemetics. Dietary modifications could potentially improve this symptom experience. Clinicians frequently provide dietary advice to patients, although the evidence base of such suggestions or recommendations is not clear. PURPOSE: This systematic review aimed to examine the current literature on food interventions associated with improvements in cancer treatment-related nausea and vomiting. METHODS: Eight electronic databases were searched with a specific search term strategy covering trials without time or language limitations. Eligible studies focused on a food substance, defined as any nutritious substance that people eat or drink to maintain life and well-being. Trials in children and adults during chemotherapy or radiotherapy were included. Cochrane risk of bias tool was used to assess trial quality and GRADE was used to assess the certainty in the effect of each outcome. RESULTS: Seventeen trials were included, 3 focusing on children and 14 on adults. Two trials included patients receiving radiation. Ten out of 17 trials (59%) had a high risk of bias. Strongest evidence with highest certainty was found for dietary counseling to meet macronutrient requirements in reducing incidence of radiotherapy-related nausea and vomiting in adults (n=2 studies; n=124 participants; GRADE level: moderate). There was also moderate certainty in the beneficial effect of protein supplementation on nausea and vomiting incidence in adults during radiotherapy (n=2 studies; n=124 participants; GRADE level: moderate). A significant positive effect on CINV incidence and/or severity in adults was also found for dietary counseling to meet macronutrient requirements during chemotherapy, a peppermint drink, scaly wood mushroom, chamomile, protein with ginger, and a colorless odorless diet (GRADE level: low to very low). CONCLUSIONS: The review identified food-based approaches that could improve the nausea and vomiting experience in patients with cancer and provide guidance to clinicians. However, confidence in these findings was low and studies were heterogeneous and mostly of low quality, requiring further investigation before stronger recommendations can be made. Future research is needed to confirm efficacy and safety. TRIAL REGISTRATION: PROSPERO CRD42022341154.

Evaluation of COVID-19 impact on DELAYing diagnostic-therapeutic pathways of lung cancer patients in Italy (COVID-DELAY study): fewer cases and higher stages from a real-world scenario.

INTRODUCTION: COVID-19 has disrupted the global health care system since March 2020. Lung cancer (LC) patients (pts) represent a vulnerable population highly affected by the pandemic. This multicenter Italian study aimed to evaluate whether the COVID-19 outbreak had an impact on access to cancer diagnosis and treatment of LC pts compared with pre-pandemic time. METHODS: Consecutive newly diagnosed LC pts referred to 25 Italian Oncology Departments between March and December 2020 were included. Access rate and temporal intervals between date of symptoms onset and diagnostic and therapeutic services were compared with the same period in 2019. Differences between the 2 years were analyzed using the chi-square test for categorical variables and the Mann-Whitney U test for continuous variables. RESULTS: A slight reduction (-6.9%) in newly diagnosed LC cases was observed in 2020 compared with 2019 (1523 versus 1637, P = 0.09). Newly diagnosed LC pts in 2020 were more likely to be diagnosed with stage IV disease (P < 0.01) and to be current smokers (someone who has smoked more than 100 cigarettes, including hand-rolled cigarettes, cigars, cigarillos, in their lifetime and has smoked in the last 28 days) (P < 0.01). The drop in terms of new diagnoses was greater in the lockdown period (percentage drop -12% versus -3.2%) compared with the other months included. More LC pts were referred to a low/medium volume hospital in 2020 compared with 2019 (P = 0.01). No differences emerged in terms of interval between symptoms onset and radiological diagnosis (P = 0.94), symptoms onset and cytohistological diagnosis (P = 0.92), symptoms onset and treatment start (P = 0.40), and treatment start and first radiological revaluation (P = 0.36). CONCLUSIONS: Our study pointed out a reduction of new diagnoses with a shift towards higher stage at diagnosis for LC pts in 2020. Despite this, the measures adopted by Italian Oncology Departments ensured the maintenance of the diagnostic-therapeutic pathways of LC pts.

The lung immuno-oncology prognostic score (LIPS-3): a prognostic classification of patients receiving first-line pembrolizumab for PD-L1 ≥ 50% advanced non-small-cell lung cancer.

BACKGROUND: To stratify the prognosis of patients with programmed cell death-ligand 1 (PD-L1) ≥ 50% advanced non-small-cell lung cancer (aNSCLC) treated with first-line immunotherapy. METHODS: Baseline clinical prognostic factors, the neutrophil-to-lymphocyte ratio (NLR), PD-L1 tumour cell expression level, lactate dehydrogenase (LDH) and their combination were investigated by a retrospective analysis of 784 patients divided between statistically powered training (n = 201) and validation (n = 583) cohorts. Cut-offs were explored by receiver operating characteristic (ROC) curves and a risk model built with validated independent factors by multivariate analysis. RESULTS: NLR < 4 was a significant prognostic factor in both cohorts (P < 0.001). It represented 53% of patients in the validation cohort, with 1-year overall survival (OS) of 76.6% versus 44.8% with NLR > 4, in the validation series. The addition of PD-L1 ≥ 80% (21% of patients) or LDH < 252 U/l (25%) to NLR < 4 did not result in better 1-year OS (of 72.6% and 74.1%, respectively, in the validation cohort). Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 [P < 0.001, hazard ratio (HR) 2.04], pretreatment steroids (P < 0.001, HR 1.67) and NLR < 4 (P < 0.001, HR 2.29) resulted in independent prognostic factors. A risk model with these three factors, namely, the lung immuno-oncology prognostic score (LIPS)-3, accurately stratified three OS risk-validated categories of patients: favourable (0 risk factors, 40%, 1-year OS of 78.2% in the whole series), intermediate (1 or 2 risk factors, 54%, 1-year OS 53.8%) and poor (>2 risk factors, 5%, 1-year OS 10.7%) prognosis. CONCLUSIONS: We advocate the use of LIPS-3 as an easy-to-assess and inexpensive adjuvant prognostic tool for patients with PD-L1 ≥ 50% aNSCLC.

KEAP1-driven co-mutations in lung adenocarcinoma unresponsive to immunotherapy despite high tumor mutational burden.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have demonstrated significant overall survival (OS) benefit in lung adenocarcinoma (LUAD). Nevertheless, a remarkable interpatient heterogeneity characterizes immunotherapy efficacy, regardless of programmed death-ligand 1 (PD-L1) expression and tumor mutational burden (TMB). KEAP1 mutations are associated with shorter survival in LUAD patients receiving chemotherapy. We hypothesized that the pattern of KEAP1 co-mutations and mutual exclusivity may identify LUAD patients unresponsive to immunotherapy. PATIENTS AND METHODS: KEAP1 mutational co-occurrences and somatic interactions were studied in the whole MSKCC LUAD dataset. The impact of coexisting alterations on survival outcomes in ICI-treated LUAD patients was verified in the randomized phase II/III POPLAR/OAK trials (blood-based sequencing, bNGS cohort, N = 253). Three tissue-based sequencing studies (Rome, MSKCC and DFCI) were used for independent validation (tNGS cohort, N = 289). Immunogenomic features were analyzed using The Cancer Genome Atlas (TCGA) LUAD study. RESULTS: On the basis of KEAP1 mutational co-occurrences, we identified four genes potentially associated with reduced efficacy of immunotherapy (KEAP1, PBRM1, SMARCA4 and STK11). Independent of the nature of co-occurring alterations, tumors with coexisting mutations (CoMut) had inferior survival as compared with single-mutant (SM) and wild-type (WT) tumors (bNGS cohort: CoMut versus SM log-rank P = 0.048, CoMut versus WT log-rank P < 0.001; tNGS cohort: CoMut versus SM log-rank P = 0.037, CoMut versus WT log-rank P = 0.006). The CoMut subset harbored higher TMB than the WT disease and the adverse significance of coexisting alterations was maintained in LUAD with high TMB. Significant immunogenomic differences were observed between the CoMut and WT groups in terms of core immune signatures, T-cell receptor repertoire, T helper cell signatures and immunomodulatory genes. CONCLUSIONS: This study indicates that coexisting alterations in a limited set of genes characterize a subset of LUAD unresponsive to immunotherapy and with high TMB. An immune-cold microenvironment may account for the clinical course of the disease.

Osimertinib beyond disease progression in T790M EGFR-positive NSCLC patients: a multicenter study of clinicians' attitudes.

BACKGROUND: In most cases, T790M EGFR-positive NSCLC patients receiving osimertinib developed "non-drugable" progression, as the patients with common EGFR-sensitizing mutations were treated with first-line osimertinib. In both settings, chemotherapy represents the standard treatment and local ablative treatments (LATs) are potential useful options in the case of oligo-progression. METHODS: We conducted a study on "post-progression" (pp) outcomes of T790M EGFR-positive NSCLC patients treated with osimertinib, according to the therapeutic strategy applied: osimertinib beyond progression (± LATs), "switched therapies" or best supportive care only (BSC). RESULTS: 144 consecutive patients were evaluated: 53 (36.8%) did not received post-progression treatments (BSC), while 91 (63.2%) patients received at least 1 subsequent treatment; 50 patients (54.9%) received osimertinib beyond disease progression [19 (20.9%) of them with adjunctive LATs] and 41 (45.1%) a switched therapy. Median ppPFS (progression-free survival) and median ppOS (overall survival) of patients who received osimertinib beyond progression vs. switched therapies were 6.4 months vs. 4.7 months, respectively [HR 0.57 (95% CI 0.35-0.92), p = 0.0239] and 11.3 months vs 7.8 months, respectively [HR 0.57 (95% CI 0.33-0.98), p = 0.0446]. Among patients who received osimertinib beyond progression with and without LATs median ppPFS was 6.4 months and 5.7 months, respectively [HR 0.90 (95% CI 0.68-1.18), p = 0.4560], while median ppOS was 20.2 months and 9.9 months, respectively [HR 0.73 (95% CI 0.52-1.03), p = 0.0748]. At the univariate analysis, the only factor significantly related to the ppPFS was the therapeutic strategy in favor of osimertinib beyond progression (± LATs). Moreover, the only variable which was significantly related to ppOS at the multivariate analysis was osimertinib beyond progression (± LATs). CONCLUSION: Our study confirmed that in clinical practice, in case of "non-druggable" disease progression, maintaining osimertinib beyond progression (with adjunctive LATs) is an effective option.

Allergic bronchopulmonary aspergillosis as presenting sign of cystic fibrosis in an elderly man.

BACKGROUND: Although cystic fibrosis is the most common genetic disorder of children, its heterogeneous spectrum of severity lends itself to underdiagnosis in the older adult patient population where the index of suspicion is not high. METHODS: We report a 60-year-old Hispanic man with asthma who presented with progressive dyspnea and wheezing unresponsive to inhaled corticosteroid treatment. Additionally, he had clinical findings and a past history suggestive of cystic fibrosis. Skin testing, radiography and laboratory studies were completed to evaluate for allergic bronchopulmonary aspergillosis (ABPA) and cystic fibrosis. RESULTS: Test results revealed peripheral eosinophilia and hyper IgE. Skin testing to Aspergillus fumigatus (Af) was positive. IgG, IgM, and Af specific antibodies were present. High resolution CT scan showed central bronchiectasis. Sweat tests were positive on two separate occasions and gene analysis showed our patient to have a positive gene mutation at D127ON/D127ON. CONCLUSION: Cystic fibrosis should be suspected in the older adult patient with a compatible clinical presentation.

ANCA in dialysis patients: a role for bioincompatibility?

UNLABELLED: BACKGROUND. Anti-neutrophil cytoplasmic autoantibodies (ANCA) have been described in patients suffering from systemic vasculitis such as Wegener granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome and other pathological conditions. In this paper we report a greater incidence of ANCA in hemodialysis patients as compared to peritoneal dialysis patients, pre-dialytic uremic patients and non-renal patients; a possible role for dialysis bioincompatibility in ANCA generation was also investigated. METHODS: A total of 335 uremics in substitutive treatment (176 in hemodialytic treatment and 159 in peritoneal dialysis) were examined for ANCA positivity. A total of 189 patients with advanced renal failure in conservative treatment and 100 healthy subjects were used as control. The dialysis techniques were standard hemodialysis (n = 119), low volume hemodiafiltration (n = 26) and hemofiltration (n = 31). ANCA positivity was examined by immunofluorescence (IF): diffuse finely granular staining was considered as classical positive reaction (C-ANCA) and P-ANCA was diagnosed if a perinuclear staining was observed. EIA for proteinase-3 (anti PR-3) and myeloperoxidase-antibodies (anti-MPO) were also performed. RESULTS: In non-renal patients and in patients with pre-dialytic renal insufficiency none were found ANCA positive. In peritoneal dialysis patients all but one were ANCA negative with IF, with all EIA test resulting negative. In hemodialytic patients, a positive IF test was found in 26 (14.7%) for P-ANCA and in 5 (2.8%) for C-ANCA; using the EIA test 23 (13%) patients were positive for MPO and 12 (6.8%) for PR-3. CONCLUSIONS: No correlation with age, primary renal diseases, dialytic age, dialysis membrane materials was found; regarding the different extracorporeal dialytic techniques a higher incidence (p < 0.02) was detected in patients undergoing HDF Backfiltration of contaminated dialysate may induce ANCA via an increased cytokine generation.

Risk factors for human T cell lymphotropic virus type II infection among the Guaymi Indians of Panama.

To examine risk factors for human T cell lymphotropic virus type II (HTLV-II) infection, a case-control study was conducted among the Guaymi Indians of Panama. In females, HTLV-II seropositivity was associated with early sexual intercourse (15 years; odds ratio [OR], 2.50; 95% confidence interval [CI], 1.11-6.14) and number of lifetime sex partners. One partner increased risk of seropositivity by 30% (OR, 1.30; CI, 1.05-1.64), and risk increased with number of partners. Similar risk was associated with number of long-term sexual relationships. Among males, intercourse with prostitutes was associated with HTLV-II seropositivity (OR, 1.68; CI, 1.04-2.72). These data support a role for sexual transmission in HTLV-II infection. Association of seropositivity with primary residence in a traditional village (OR, 3.75; CI, 1.02-15.38) and lack of formal education (0 vs. >6 years [OR, 3.89; CI, 1.67-9.82]) observed in males may reflect differences in sexual practices associated with acculturation.

Evidence of exercise-induced myocardial ischemia in patients with primary aldosteronism: the Cross-sectional Primary Aldosteronism and Heart Italian Multicenter Study.

BACKGROUND: Primary aldosteronism (PA) is a disease associated with hypersecretion of aldosterone caused by an aldosterone-producing adrenal adenoma, bilateral adrenal hyperplasia, and, although rarely, by adrenal carcinoma. Arterial hypertension induces several cardiovascular alterations that yield a high cardiovascular risk. It has been shown that reduced myocardial perfusion at rest, assessed by thallium-201 myocardial scintigraphy, was greater in PA than in essential hypertension (EH). However, it is still unknown whether reduced myocardial perfusion at rest and/or regional function abnormalities are present during exercise-induced myocardial stress. PURPOSE: We addressed the impact of PA on myocardial ischemia and sought to identify signs of exercise-induced myocardial ischemia (assessed by MIBI-SPECT and echocardiography) in patients with PA compared to patients with EH. Patients with consistent signs of myocardial ischemia on all of the tests were studied by coronary arteriography. PATIENTS: We studied 72 patients with PA and an age/sex-matched group of 72 patients with EH enrolled in the cross-sectional Primary Aldosteronism and Heart Italian Multicenter Study (PAHIMS). METHODS: Regional function was detected from echocardiographic measurement of wall motion done at baseline and immediately after exercise. Myocardial perfusion was evaluated by SPECT imaging after injecting 99mTc-MIBI with the same-day protocol using the rest-stress sequence. RESULTS: Although the conditions of arterial pressure, duration of hypertension, and target organ damage were equivalent, the patients with PA had greater incidence of both reversible perfusion defects and abnormalities of regional function. Moreover, multiple regression analysis showed that the high plasma aldosterone level was highly predictive for SPECT ischemic score and wall motion index, suggesting that PA contributes to cardiovascular risk over and above that associated with ventricular hypertrophy. Exercise-induced myocardial ischemia in PA was not segmental but widely distributed suggesting that this phenomenon was not related to abnormal coronary perfusion. Accordingly, of the 38 patients with PA who underwent coronarography, there was no presence of significant coronary atherosclerotic lesions in 30 (78.9%) of the patients. CONCLUSIONS: The PAHIMS observed more exercise-induced moderate myocardial ischemic defects (co-detected by SPECT and echocardiograms and not segmental but widely allocated) in patients with PA than in patients with EH. This phenomenon occurred in a greater percentage of patients with PA without significant coronary lesions (78.95%, n = 38), which supports the possible presence of small-vessel intramyocardial disease.