Utility of Prophylactic Percutaneous Gastrostomy in Patients With Head and Neck Cancer Receiving Concurrent Chemoradiotherapy: A Multicenter Analysis.

INTRODUCTION: Patients with head and neck cancer (HNC) have an elevated incidence of cachexia and malnutrition due to the tumor's location interfering with oral feeding. Concurrent chemoradiation (CCRT) can have an emetic effect and cause dysphagia and oral mucositis. Adequate nutrition improves immunity, raises the response to therapy, reduces adverse effects, and improves survival. Numerous studies have suggested the utility of nutritional support from percutaneous endoscopic gastrostomy (PEG) in HNC patients. Although PEG is usually considered a safe procedure, it has a mortality rate of 0-2.2% and a risk of other procedure-related complications of 17-40%. Our work intends to evaluate the utility of PEG in patients with locally advanced HNC who underwent CCRT. METHODS: We performed a cohort study at three institutions. We included patients with HNC who underwent definitive CCRT treatment from January 2013 to December 2022. The study consisted of an observational, descriptive, retrospective analysis of prespecified clinical data. Descriptive statistics were used to compare the data between the PEG group and the non-PEG group. Analysis of covariance (ANCOVA) was used for covariance analysis. Fisher's exact test was used to compare proportional data and Student's t-test was used to assess the differences in continuous data. Survival analysis was performed using the Kaplan-Meier estimator. P-values of <0.05 were considered to be indicative of statistical significance. The SPSS Statistics version 28.0 (Armonk, NY: IBM Corp.) was used to perform all statistical evaluations. RESULTS:  We identified 90 eligible patients diagnosed with local advanced HNC who had received definitive CCRT with three weekly cycles of cisplatin as follows: 44 with a prophylactic PEG tube and 46 without a prophylactic PEG tube. Most patients were male (84.4%) and 50% of patients were diagnosed with stage IVa HNC at the time of diagnosis. There wasn't an effect of PEG placement on BMI at the end of CCRT after controlling for the effect of baseline BMI (F {1.84}=0.065 {p=0.799}). In the study population, BMI was significantly lower after CCRT (21.30 kg/m2 vs. 23.97 kg/m2), t (86)=12.389, p<0.001. In the subgroup with baseline BMI <18.5 kg/m2 (15 patients), 90% of patients with prophylactic PEG were able to complete the three planned cycles of chemotherapy vs. 66.7% in the non-PEG group. Ten patients in the PEG group (22.7%) referred feeding tube dependency. Patients with dysphagia were 3.2 times more likely to have placed prophylactic PEG (p=0.007). The difference in overall survival and progression-free survival between the two groups was not statistically significant (p=0.57 and p=0.497, respectively). CONCLUSION: In this study using real-world data, we found a potentially protective effect of PEG in underweight patients with locally advanced HNC performing CCRT in order to complete three cycles of treatment.

Prognostic Impact of Type 2 Diabetes in Metastatic Colorectal Cancer.

Background Diabetes mellitus (DM) is a prognostic factor for some malignancies, but its clinical implications in metastatic colorectal cancer (mCRC) patients are less clear. Therefore, we conducted a retrospective study to evaluate the impact of pre-existing type 2 diabetes mellitus (T2DM) on the survival outcomes of patients with newly diagnosed mCRC. Methodology We retrospectively included patients with newly diagnosed mCRC between January 2017 and June 2021 and with pre-existing T2DM. Data on the characteristics of patients, clinicopathological features, and drug exposure were collected from the electronic medical records. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS) and treatment-related adverse events (TRAEs). Results Among 187 mCRC patients, 54 (28.8%) had T2DM. The median follow-up was 25 months. We observed 150 OS events and 168 PFS events. Diabetes significantly and negatively impacted PFS and OS. The median for PFS (mPFS) was eight and 16 months for T2DM and no T2DM patients, respectively (p < 0.0001; log-rank test). The median overall survival (mOS) was 15 and 29 months for T2DM and no T2DM patients, respectively (p < 0.0001; log-rank test). Patients with diabetes were more often overweight or obese (59.3% vs. 24.8%; p < 0.01) and had a poorer performance status (53.7% vs. 21.1% with Eastern Cooperative Oncology Group Performance Status 1; p < 0.01). Additionally, T2DM patients had more high-risk pathological features, including G3 grading tumors (27.7% vs. 12.0%; p = 0.01), lymph node involvement (p < 0.01), BRAF-mutated (35.1% vs. 6.8%; p < 0.01), and right-sided CRC (63.0% vs. 30.1%; p < 0.01). We found no statistically significant differences in TRAEs. Nevertheless, a significantly higher rate of grade 2-4 peripheral neuropathy (22.2% vs. 5.3%; p < 0.01) was reported in T2DM patients. Conclusions T2DM is a negative prognostic factor for survival in mCRC. The paper provides empirical evidence in favor of the joint control of both pathologies. Further research is needed to establish the robustness of our results.

Impact of Human Epidermal Growth Factor Receptor 2 (HER2) Low Status in Response to Neoadjuvant Chemotherapy in Early Breast Cancer.

Introduction In clinical practice, there is a binary distinction between human epidermal growth factor receptor 2 (HER2)-positive and HER2-negative (HER2-) breast cancer (BC). However, within HER2- disease, there is significant heterogeneity. Particularly, HER2- tumors that express some level of HER2 by immunohistochemistry (IHC) score 1+ or 2+/in situ hybridization (ISH) non-amplified are currently defined as HER2-low. This subgroup has shown distinct biological features compared to HER2-zero (HER2-0) BC and additionally novel antibody-drug conjugate therapies have demonstrated a potential and promising activity in HER2-low BC population. This study aims to evaluate the impact of HER2-low status in response to neoadjuvant chemotherapy (NACT) in HER2- BC being HER2-low and HER2-0 status. Materials and methods In a single institution, we retrospectively reviewed clinical and pathological data of HER2 early-stage BC patients treated with NACT following definitive surgery from January 2015 to December 2020. Tumors with HER2 IHC 0 were classified as HER2-0 and IHC score 1+ and 2+/ISH non-amplified as HER2-low. The primary objective was to evaluate the rate of pathological complete response (pCR) using the definition of ypT0/Tis ypN0 according to HER2-low and HER2-0 subgroups. Secondary objectives were to evaluate biological features between the two subgroups, disease-free survival (DFS), and overall survival (OS). Pearson chi-square, Fisher's exact, and Mann-Whitney tests were performed. The Kaplan-Meier method was used to plot DFS and OS curves. A p-value of <0.05 was considered statistically significant. Results A total of 72 patients with HER2 BC were included with a median age at diagnosis of 52.5 years and a median follow-up time of 35.5 months. Of patients, 56.9% had HER2-low disease and 43.1% had HER2-0 disease. Significant differences between the two subgroups were detected regarding hormonal receptor status and proliferation grade (Ki67). In the HER2-low subgroup, 70% of tumors were luminal-like and 64.5% of HER2-0 patients had triple-negative BC (p = 0.03). There were statistically significant differences regarding estrogen (p = 0.00) and progesterone (p = 0.02) receptors. The median Ki67 rate was higher in the HER2-0 subset (mean rank = 43.9) compared to HER2-low (mean rank = 30.9) and this difference was statistically significant (p = 0.00). HER2-low patients presented more stage III tumors (65.9%) and HER2-0 patients were mainly stage II (61.3%), and this was statistically relevant (p = 0.03). The prevalence of other clinical and pathological features was comparable between both groups. HER2-low subgroup achieved lower pCR rates (14.6% vs. 29.0%) but this difference was not statistically significant (p = 0.15). Similarly, there was no difference between the two subgroups regarding DFS (p = 0.97) and OS (p = 0.35), although the data were immature. Conclusion As in prior studies, this study did not support a significant impact of HER2-low status on response to NACT in HER2- patients with early-stage BC. HER2-low patients had a lower pCR, which may suggest a worse response to classic chemotherapy regimen and may have clinical implications that should be further exploited. The prevalence of hormonal receptors in HER2-low tumors was consistent with previous data in the literature. Although retrospective, the data suggest that HER2-low tumors should be regarded as a distinct biological subtype and more research is warranted.

Association of Weight Change, Inflammation Markers and Disease Staging with Survival of Patients Undergoing Chemotherapy for Pancreatic Adenocarcinoma.

INTRODUCTION: Cancer-associated-cachexia represents a systemic syndrome of unintended weight-loss (WL) and systemic inflammation, affecting >80% patients with pancreatic adenocarcinoma (PA). We aimed to evaluate the association of weight change (WC) with survival of patients treated with chemotherapy (ChT) for PA and the influence of disease staging. We also studied the prognostic and predictive value of inflammation-based scores. METHODS: Observational, retrospective cohort study. Individuals were divided into two cohorts, according to WC (WL ≥5% vs. non-WL <5%) after ChT. Main endpoints were weight change and survival time. Statistical analysis was performed using Stata software. RESULTS: Sixty-five patients were included (median age 69; 48% female), 60% with advanced disease. At 3 months after ChT start, 54% experienced WL. Advanced disease independently predicted WL (OR 2.10; 95% CI, 1.11-19.6; p = 0.041). With median follow-up of 14.8 mo, median survival time of patients with WL was 18.5 mo, vs. 33.2 vs. for non-WL (HR 2.28; 95% CI, 1.15-4.52; p = 0.019). In patients with early-stage disease, WL was associated with decreased survival time (21.9 vs. 67.6 mo; HR 23.68; 95% CI 2.39-234.75; p = 0.007), while the association of WL on survival time in advanced disease was not significant (HR 0.74; 95% CI, 0.34-1.60; p = 0.449). The multivariate survival model showed that WL (HR 1.11, 95% CI 1.03-1.20, p = 0.005) and cachexia (HR 3.76, 95% CI 1.07-13-18), p = 0.041) were associated with survival time, as well as location in body or tail (HR 3.05; 95% CI, 1.75-5.31; p < 0.001) and high Neutrophil-to-lymphocyte ratio (NLR) at 3 months (HR 6.20; 95% CI, 2.59-14.87; p < 0.001). CONCLUSION: WL was an independent prognostic factor for survival. Particularly in early stage disease, interventions targeting this modifiable factor may translate into better outcomes for PA patients. NLR may be a surrogate marker of systemic inflammatory status in this setting.

Fecal Microbiota Transplant in Immunotherapy-Resistant Melanoma: What Can We Expect in the Near Future?

Melanoma is a malignancy of melanocytes, melanin-producing cells in the basal layer of the epidermis. Despite representing only 1% of skin cancers, melanoma is responsible for over 80% of skin cancer deaths. Treatment with immune checkpoint inhibitors (ICIs) that target the programmed death 1 (PD-1) protein and the cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathways drastically transformed the management of patients with advanced melanoma. Before the introduction of ICIs, the average life expectancy for a patient with advanced melanoma ranged from six to 12 months, and now, this average survival has increased to over six years. However, despite this outstanding clinical success, most patients with advanced melanoma treated with ICIs will experience disease progression, immediately or after an initial response to treatment. Nowadays, some studies have looked at the mechanism behind the resistance to immunotherapy, with the aim of developing new treatments to overcome it. Emerging data suggest that gut microbiota (GM) influences response to immunotherapy. Importantly, unlike tumor genomics, the GM is changeable; thus, modulation of the GM is an attractive approach to overcome immunotherapy resistance. One of these approaches is the fecal microbiota transplant (FMT), which consists of the exchange of manipulated feces from a donor to a recipient who has a disorder related to intestinal dysbiosis to directly change the recipient's gut microbial composition and confer a health benefit. This review pretends to discuss the clinical benefit of FMT in the treatment of immunotherapy-resistant melanoma and potential adverse effects, including recent and ongoing clinical trials.

Pain in an Internal Medicine Ward: An Undervalued Reality?

Introduction Pain is prevalent in most pathologic situations that require healthcare and is very common in hospitalised patients. However, there is limited evidence about the prevalence and the actual management of pain in medical wards. The aim of this work was to evaluate and characterise pain management in an internal medicine ward. Methods Retrospective analysis of clinical data of patients consecutively discharged from the internal medicine ward of a central tertiary hospital over a period of five months in 2018. Results 199 patients evaluated, the median age was 78 years and 63% were female. Of these, 14% had a previous diagnosis of chronic pain, 24% were on chronic pain medication, and in 29% medication was interrupted. Pain was noted in medical records of 118 patients, with moderate to severe intensity in 67%. Among those, 71% had pain occurrence registered in the medical notes but not characterised in duration in 61%. The most common attributed etiologies of pain were musculoskeletal (16%), visceral (9%), and headache (8%); no identifiable cause was specified in 57%. In the group of patients reporting pain, 63% received analgesics. Opioids were used in 35% and 47% of patients with moderate and severe pain, respectively. At discharge, 12 patients were still referred pain, 16 had pain listed as a diagnosis, 45 were medicated for pain, and eight were referred for pain consultation. Conclusions Despite being highly prevalent in the internal medicine ward, pain is still under-recognised, undervalued, and under-treated. Education of healthcare staff and adoption of treatment protocols is essential to improve care for these patients.

COVID-19 and aging: Identifying measures of severity.

INTRODUCTION: We aimed to compare clinical features of older age group and young and middle-aged patients with COVID-19 and analyze mortality predictors. METHODS: Retrospective analysis of ongoing collection of prespecified data, on a single institution, including patients hospitalized consecutively due to COVID-19 infection, from March to June 2020. RESULTS: Of 195 patients, 56.9% were ⩾65 years (older age group). Older age group had multimorbidity (p < 0.001). At admission Early Warning Score-2 (p < 0.001), C-reactive protein, D-dimer, creatinine, anemia and lymphopenia were higher in older age group, as well as median time of hospitalization (14 vs 10 days, p = 0.004). Complications were more common in older age group, but there were no significant differences in admission to intensive care. There were 18 deaths, 16 in older age group. Modified Early Warning Score at admission (odds ratio = 1.60, 95% confidence interval = 1.07-1.37, p = 0.021) and C-reactive protein >5 mg/dL (odds ratio = 2.12, 95% confidence interval = 1.13-26.26, p = 0.034) were independent predictors of inhospital mortality in older age group but not in young and middle-aged. CONCLUSION: Older age group was at higher risk for complications and inhospital mortality. Identification of specific scores of severity for this population is essential to ensure that best care is provided.

The Reality of Critical Cancer Patients in a Polyvalent Intensive Care Unit.

Background and objective With the increasing incidence of cancer and the rise in the survival rates of cancer patients, more and more oncological candidates are being considered for admission to intensive care units (ICU). Several studies have demonstrated no difference in the outcomes of cancer patients compared to non-cancer patients. Our study aimed to describe and analyze the outcomes related to cancer patients in a polyvalent ICU. Methods We conducted a retrospective study of consecutive oncological patients admitted to a polyvalent ICU (2013-2017). Cox model and receiver operating characteristic (ROC) curve analysis were performed to analyze the results. Results A total of 236 patients were included in the study; the mean age of the patients was 53.5 ± 15.3 years, and 65% of them were male. The main cancer types were those related to the central nervous system (CNS; 31%), as well as gastrointestinal (18%), genitourinary (17%), and hematological (15%). Curative/diagnostic surgeries (49%) and sepsis/septic shock (17%) were the main reasons for admission. The Acute Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute Physiology Score II (SAPS II) scores in hematological patients vs. solid tumors were as follows: 30 vs. 20 and 63 vs. 38, respectively (p<0.005). Vasopressors, invasive mechanical ventilation (IMV), and renal replacement therapy (RRT) were used more widely in hematological patients compared to solid-tumor patients. Length of stay was longer in hematological patients vs. solid-tumor patients (12.8 vs. 7 days, p=0.002). The median overall survival in hematological patients was one month and that in solid-tumor patients was 5.8 months (p<0.005). The survival rate at six months was better than described in the existing literature (48 vs. 32.4%). Conclusion Both SAPS II and APACHE II scores were reasonably accurate in predicting mortality, demonstrating their value in cancer patients.

From Theory to Practice: Bone Health in Women with Early Breast Cancer Treated with Aromatase Inhibitors.

Aromatase inhibitors (AI) are extensively used as adjuvant endocrine therapy in post-menopausal women with hormone receptor-positive early breast cancer (HR+ EBC), but their impact on bone health is not negligible. This work aimed to assess bone loss, fracture incidence, and risk factors associated with these events, as well as the prognostic influence of fractures. We have conducted a retrospective cohort study of women with HR+ EBC under adjuvant therapy with AI, during a 3-year period. Four-hundred-and-fifty-one eligible women were reviewed (median age 68 years). Median time under AI was 40 months. A fracture event occurred in 8.4%, mostly in the radium and femoral neck and in older women (mean 74 vs. 68 years, p = 0.006). Age (OR 1.01, 95% CI 1.01-1.07, p = 0.024) and time under AI (OR 1.02, 95% CI 1.00-1.04, p = 0.037) were independent predictors of fracture, with a fair discrimination (AUC 0.71). Analysis of disease-free survival according to fracture event varied between groups, disfavoring the fracture cohort (at 73 months, survival 78.6%, 95% CI, 47.6-92.4 vs. 95.6%, 95% CI, 91.2-97.8, p = 0.027). The multivariate model confirmed the prognostic impact of fracture occurrence (adjusted HR of 3.17, 95% CI 1.10-9.11; p = 0.032). Bone health is often forgotten, despite its great impact in survivorship. Our results validate the pathophysiologic link between EBC and bone metabolism, which translates into EBC recurrence. Further research in this area may help refine these findings. Moreover, early identification of women at higher risk for fractures is warranted.