Can we counterbalance restricted access to innovation through specialized breast cancer care? The REAL-NOTE study.

INTRODUCTION: The KEYNOTE-522 (KN-522) trial showed that the addition of pembrolizumab to standard chemotherapy improved pathological complete response (pCR) and event-free survival (EFS) for patients with early triple negative breast cancer (TNBC). We analyzed results of a real-world cohort of patients treated in a certified Breast Unit, before the introduction of pembrolizumab, to see if high quality care can match outcomes brought by the addition of an innovative anticancer therapy. METHODS: Observational, retrospective, single-center cohort study, with real-world data from an ongoing institutional database with prespecified variables. Inclusion criteria matched the ones from KN-522: previously untreated stage II or III TNBC, diagnosed between 2012 and 2022, who received neoadjuvant chemotherapy. The primary endpoints were pCR at the time of definitive surgery and EFS; overall survival (OS) was a secondary endpoint. RESULTS: Total of 168 patients were included, median age 55 years, 55 % received neoadjuvant chemotherapy with dose dense anthracyclines and taxanes and 25 % carboplatin + paclitaxel, sequenced with dose dense anthracyclines. Most had Stage II disease (82.7 %), 47 % node + disease. pCR was achieved in 52.7 % cases. At 36 months, EFS was 83.3 % (95 % CI 75.1-89.0) and OS 89 % (95 % CI, 81.6 to 93.5). CONCLUSIONS: Notwithstanding the study limitations, outcomes of patients treated with chemotherapy without immunotherapy were numerically similar to the experimental arm of KN-522 trial. These data highlight that providing care by a specialized multidisciplinary team in a certified unit might be just as impactful as the incorporation of new technologies.

Effects of exercise training on cancer patients undergoing neoadjuvant treatment: A systematic review.

OBJECTIVES: This systematic review aimed to analyze the effects of different exercise protocols on physical fitness (cardiorespiratory fitness, muscle strength, and body composition), quality of life, cancer-related fatigue, and sleep quality in patients with different types of cancer undergoing neoadjuvant treatment. DESIGN: Systematic review. METHOD: A comprehensive search of existing literature was carried out using four electronic databases: PubMed, Scopus, Web of Science, and Cochrane Library (published until October 19, 2022). All databases were searched for randomized controlled trials, quasi-experimental investigations, and pre-post investigations assessing the effects of exercise in cancer patients during neoadjuvant treatment. Excluded articles included multicomponent interventions, such as exercise plus diet or behavioral therapy, and investigations performed during adjuvant treatment or survivorship. The methodological quality of each study was assessed using the Physiotherapy Evidence Database (PEDro) scale. RESULTS: Twenty-seven trials involving 999 cancer patients were included in this review. The interventions were conducted in cancer patients undergoing neoadjuvant treatment for rectal (n = 11), breast (n = 5), pancreatic (n = 4), esophageal (n = 3), gastro-esophageal (n = 2), and prostate (n = 1) cancers, and leukemia (n = 1). Among the investigations included, 14 utilized combined exercise protocols, 11 utilized aerobic exercise, and two utilized both aerobic and resistance training separately. Exercise interventions appeared to improve cardiorespiratory fitness, muscle strength, body composition, and quality of life, although many investigations lacked a between-group analysis. CONCLUSION: Despite limited evidence, exercise interventions applied during neoadjuvant treatment demonstrate promising potential in enhancing cardiorespiratory fitness, muscle strength, body composition, and overall quality of life. However, a scarcity of evidence remains on the effects of exercise on cancer-related fatigue and sleep quality. Further research with high-quality randomized controlled trials is warranted.

Effects of home-based exercise programs on physical fitness in cancer patients undergoing active treatment: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: This systematic review and meta-analysis aimed to investigate the effects of home-based exercise on physical fitness (cardiorespiratory fitness, muscle strength, and body composition) in cancer patients undergoing active treatment. DESIGN: Systematic review with meta-analysis and Grading Recommendations Assessment, Development, and Evaluation of the evidence. METHODS: A comprehensive search of existing literature was carried out in four electronic databases: PubMed, Web of Science, Scopus, and PEDro. All databases were searched for randomized controlled trials assessing the effects of home-based exercise on physical fitness outcomes in cancer patients during active treatment. Multicomponent interventions (i.e., exercise plus diet/behavioral therapy) were excluded. The methodological quality of each study was assessed using the Revised Cochrane risk-of-bias tool for randomized trials. Meta-analytical procedures were performed when appropriate and standardized mean differences (SMD) were calculated. RESULTS: Twenty-eight randomized controlled trials (n = 2424 cancer patients) were included. Most of the interventions were conducted in breast cancer patients (n = 13) during the adjuvant treatment period (n = 17); 18 studies included a walking component in their home-based protocol. Home-based exercise was effective at improving the distance of the 6-minute walk test (k = 6; SMD = 0.321, p = 0.010). However, the results were no longer significant when performing sensitivity analysis based on exclusively walking (k = 1) and non-exclusively walking interventions (k = 5; SMD = 0.258; p = 0.072). No effects were found for muscle strength and body composition outcomes (p > 0.05). CONCLUSIONS: Regular home-based exercise programs are an effective strategy to improve 6-minutes walk test in cancer patients undergoing active treatment. Conversely, no alterations were found in muscle strength and body composition.

Necrotizing fasciitis of the vulva due to carbapenem-resistant Enterobacteriaceae as a complication of acute myeloid leukemia treatment: a case report.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae strains have been reported in healthcare facilities with a rising incidence and are a major concern owing to infections that are often severe and can be potentially fatal, with limited therapeutic options. Klebsiella pneumonia represents the most frequently isolated microorganism. CASE PRESENTATION: We report the case of a Caucasian 52-year old Caucasian woman with acute myeloid leukemia was admitted to the inpatient hematology unit at a university referral hospital in Portugal. This hospital has endemic colonization of Carbapenem-resistant Enterobacteriaceae and contention measures are being implemented to reduce spreading of these multidrug resistant bacteria. After receiving first line chemotherapy according to the intermediate-dose cytarabine regimen, in context of deep medullary aplasia, the patient developed a localized infection of the vulva, which progressed to a necrotizing fasciitis. This is a rare, life-threatening, and fulminant infection. Carbapenem-resistant Klebsiella was isolated in both vulvar exudate and blood cultures. The patient underwent multiple schemes of antimicrobials, but progressed with multiorgan compromise and was admitted to the intensive care unit for a short period for stabilization. Surgical debridement was performed twice with clinical improvement and, after 6 weeks, a skin graft was executed with good response. Reevaluation of the hematologic disease showed a complete response to first cycle of induction therapy. Despite success in resolving this complex infection, decisions regarding antibiotic treatment represented a tremendous challenge for the whole team. The importance of multidisciplinary collaboration was key for the patient's recovery and survival, and therefore, needs to be acknowledged. CONCLUSIONS: This clinical case raises awareness on a clinical entity that can be life threatening and, therefore, requires a high level of suspicion to assure an early integrated approach to avoid complications. Endemic spreading of carbapenem-resistant Enterobacteriaceae is becoming a reality, and health policies need to be urgently undertaken at the national level to decrease morbidity and mortality because of health facilities-related infections.

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.

Endocrine therapy for the treatment of leptomeningeal carcinomatosis in luminal breast cancer: a comprehensive review.

Leptomeningeal disease (LMD) represents a devastating complication of advanced breast cancer (ABC), with survival of <5 months with multimodal treatment. The role of endocrine therapy (ET), due to its favorable toxicity profile and first-line indication in luminal ABC, appears promising in the setting of LMD, where symptom stabilization and quality-of-life preservation are the main goals; however, evidenced-based data are lacking. We conducted a thorough review of published evidence, aiming to investigate the role of ET in LMD treatment in luminal ABC. Twenty-one of 342 articles, evaluating 1302 patients, met inclusion criteria. ET use was rarely reported. New targeted agents show CNS activity. Research is lacking on the role of ET and targeted agents in BC-LMD treatment.

Sweet's Syndrome Induced by Aromatase Inhibitor in the Treatment of Early Breast Cancer.

BACKGROUND: Breast cancer is the most commonly diagnosed cancer in women, mainly at an early stage, allowing treatment with curative intent. Aromatase inhibitors are widely used in the adjuvant treatment of oestrogen receptor-positive breast cancer, mainly in postmenopausal women. The most frequent adverse events associated with these therapies are musculoskeletal symptoms and an increased risk of bone fractures. Cutaneous adverse events have been rarely described. Sweet's syndrome can present as an idiopathic disorder in addition to being malignancy-associated or drug-induced. CASE PRESENTATION: We report the case of a 69-year old woman, diagnosed with early stage breast cancer, who underwent breast-conserving surgery, followed by adjuvant radio and endocrine treatment with letrozole 2.5 mg daily, for a foreseeable duration of 5 years. Three months after starting letrozole, she presented with sudden fever and exuberant and painful erythematous skin papules and plaques on her upper body. After a full work-up and exclusion of other potential causes, a skin biopsy confirmed the presence of dermal oedema and a diffuse neutrophilic infiltrate, suggesting Sweet's syndrome. After discontinuation of letrozole and treatment with corticosteroids, the patient fully recovered. She resumed adjuvant treatment with tamoxifen, without symptom recurrence. CONCLUSIONS: Sweet's syndrome is a rare condition and an association with aromatase inhibitors has not been previously reported. Although its occurrence has already been observed in the onset of malignancies such as breast cancer, aromatase inhibitors must be added to the list of potential causes of drug-induced Sweet's syndrome. LEARNING POINTS: Aromatase inhibitors are widely used in the treatment of breast cancer and, though infrequent, it is important to recognize possible cutaneous adverse events.Sweet's syndrome is a rare but troublesome condition. Prompt recognition and management are crucial to alleviate symptoms.Drug-induced Sweet's syndrome associated with aromatase inhibitors has not been previously reported and should be considered when evaluating treatment toxicities.

Metastatic extramammary paget disease, a remarkable clinical case and a brief review of a rare disease.

Extramammary Paget Disease (EMPD) is an often-misdiagnosed rare disorder, whose cause remains unknown. Diagnosis is confirmed by skin biopsy. Primary treatment for EMPD is surgery. Recurrence is common in the first two years and prognosis is good if the disease is localized and there is no underlying associated cancer. Patients with invasive and metastatic EMPD are uncommon and exhibit a poor prognosis, even when there is good response to a first chemotherapy line. Multiple chemotherapeutic regimens, with varying levels of success, have been attempted, but standard of care is not established. The central nervous system seems to be a common metastatic site with better survival than visceral metastasis.We report a case of metastatic EMPD that addresses the difficulties associated with the treatment of this rare disease, that has no current guidelines.

Severe rhabdomyolysis related to oxaliplatin adjuvant therapy for colorectal cancer.

Colorectal cancer is the third most common cancer in men and the second in women. The standard chemotherapy regiment in stage III colon cancer is based in oxaliplatin. The most common side effects include neutropenia, peripheral neuropathy, vomiting and diarrhoea. Rhabdomyolysis due to oxaliplatin is rare, and there are no established guidelines for managing this adverse event. This report describes a case of a 52-year-old man, with a resected stage III colon cancer that started postoperative adjuvant chemotherapy with capecitabine plus oxaliplatin. After the second cycle, the patient developed distal muscle pain and weakness, with a total inability to walk. Blood tests showed an elevated creatine kinase and renal injury. Severe drug-related rhabdomyolysis was diagnosed. The goal of this case report is to discuss the side effect of adjuvant chemotherapy, given its rarity and severity.

Palliative Sedation in Terminal Cancer Patients Admitted to Hospice or Home Care Programs: Does the Setting Matter? Results From a National Multicenter Observational Study.

CONTEXT: Few studies regarding palliative sedation (PS) have been carried out in home care (HC) setting. A comparison of PS rate and practices between hospice (HS) and HC is also lacking. OBJECTIVES: Comparing HC and HS settings for PS rate, patient clinical characteristics before and during PS, decision-making process, and clinical aspects of PS. METHODS: About 38 HC/HS services in Italy participated in a multicenter observational longitudinal study. Consecutive adult cancer patients followed till death during a four-month period and undergoing PS were eligible. Symptom control and level of consciousness were registered every eight hours to death. RESULTS: About 4276 patients were screened, 2894 followed till death, and 531 (18%) underwent PS. PS rate was 15% in HC and 21% in HS (P < 0.001). Principal refractory symptoms were delirium (54%) and dyspnea (45%), respectively, more common in HC (P < 0.001) and HS (P = 0.03). Informed consent was not obtained in 72% of patients but achieved by 96% of families. Midazolam was the most used drug (94% HS vs. 75% HC; P < 0.001) mainly by continuous infusion (74% HC vs. 89% HS; P < 0.001). PS duration was less than 48 hours in 67% of patients. Hydration during PS was less frequent in HC (27% vs. 49%; P < 0.001). In the eight hours before death, consciousness level was unrousable to mild physical stimulation in 81% and symptom control complete in 89% of cases. CONCLUSION: Our results show feasibility of PS in HC and HS and suggest setting differences in rates, indications, and practice of PS, possibly related to patients' selection or care organization.