Safety and efficacy of ribociclib plus letrozole in patients with HR+, HER2– advanced breast cancer: Results from the Spanish sub-population of the phase 3b CompLEEment-1 trial

BackgroundBreast cancer is the most common malignancy and the second leading cause of cancer-related mortality in Spanish women. Ribociclib in combination with endocrine therapy (ET) has shown superiority in prolonging survival in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC) vs. ET alone.MethodsCompLEEment-1 is a single-arm, open-label phase 3b trial evaluating ribociclib plus letrozole in a broad population of patients with HR+, HER2– ABC. The primary endpoints were safety and tolerability. Here we report data for Spanish patients enrolled in CompLEEment-1.ResultsA total of 526 patients were evaluated (median follow-up: 26.97 months). Baseline characteristics showed a diverse population with a median age of 54 years. At study entry, 56.5% of patients had visceral metastases and 8.7% had received prior chemotherapy for advanced disease. Rates of all-grade and Grade ≥3 adverse events (AEs) were 99.0% and 76.2%, respectively; 21.3% of patients experienced a serious AE, and 15.8% of AEs led to treatment discontinuation. AEs of special interest of neutropenia, increased alanine aminotransferase, increased aspartate aminotransferase and QTcF prolongation occurred in 77.8%, 14.8%, 11.4% and 4.0% of patients, respectively. Patients aged >70 years experienced increased rates of all-grade and Grade ≥3 neutropenia and anemia. Efficacy results were consistent with the global study.ConclusionsResults from Spanish patients enrolled in CompLEEment-1 are consistent with global data showing efficacy and a manageable safety profile for ribociclib plus letrozole treatment in patients with HR+, HER2− ABC, including populations of interest (NCT02941926).Trial registrationClinicalTrials.gov NCT02941926     

Clinical outcome of adjuvant radiotherapy for squamous cell carcinoma of the breast; a multicenter retrospective cohort study

BackgroundBecause primary squamous cell carcinoma (SCC) of the breast is a rare disease, the standard therapy has not been established. We examined the clinical outcomes of postoperative adjuvant radiotherapy for breast SCC.Material and methodsWe conducted a multicenter retrospective cohort study. Patients diagnosed with primary breast SCC who received adjuvant radiotherapy as part of their primary definitive treatment were included. Overall survival (OS), breast cancer-specific survival (BCSS), and recurrence-free interval (RFi) were evaluated.ResultsBetween January 2002 and December 2017, 25 breast SCC patients received adjuvant radiotherapy as a primary treatment were included. Median follow-up time was 43.5 months. Three (12%), fifteen (60%) and seven (28%) patients had clinical stage I, II and III disease, respectively. Fourteen patients underwent breast-conserving surgery and subsequent adjuvant radiotherapy. Eleven patients underwent mastectomy and post-mastectomy radiotherapy. Ten patients received regional lymph node irradiation. Nine (36%) patients had disease recurrence. The first site of recurrence was locoregional in five, but distant metastasis arose in one. Concurrent local and distant metastasis were seen in two. Six cases of local recurrence occurred within the irradiated site. Seven patients died, and six of the deaths were due to breast cancer. Five-year OS, BCSS, and Rfi were 69%, 70%, and 63%, respectively. In multivariate analysis, age and lymphatic invasion were associated with increased risk of recurrence.ConclusionBreast SCC has a high incidence of locoregional recurrence and poor prognosis. Age and lymphatic invasion are significant risk factors for recurrence.     

Long-term survival after xenograft versus homograft aortic root replacement: Results from a prospective randomized trial

ObjectiveThe study objective was to investigate the long-term survival of patients undergoing xenograft versus homograft full root aortic valve replacement.MethodsA total of 166 patients requiring aortic valve surgery were randomized to undergo the Freestyle (Medtronic Inc, Minneapolis, Minn) bioprosthesis (N = 90) or a homograft (N = 76) full root aortic valve replacement between 1997 and 2005 in a single institution. Six patients randomly assigned to the homograft crossed over to the Freestyle bioprosthesis because of the unavailability of suitably sized homografts. All surgeons were required to adhere to the standard surgical technique for homograft root implantation previously described. Follow-up was 98.5% complete.ResultsThe mean age of the study population was 65 ± 8 years. Coronary artery bypass grafting was associated with root aortic valve replacement in 76 of 166 patients (46%, P = not significant between groups), and overall hospital mortality was 4.8% (8/166, P = not significant between groups). Median follow-up was 13.8 years (range, 0-21.8 years; 2033 patient-years). The Kaplan–Meier survival analysis showed that there was no significant difference in overall survival between the 2 arms at 5, 10, and 15 years. Twenty-year survival was 28.3% ± 5% for the Freestyle group versus 25.1% ± 5.7% for the homograft group (P = .90), which was comparable to the age- and sex-matched UK general population. The freedom from aortic valve reoperation at 20 years was comparable for the Freestyle group versus the homograft group (67.9% ± 8.8% vs 67.2% ± 10.3%, respectively; P = .74).ConclusionsThis is the first study to investigate the long-term survival of xenograft versus homograft full root aortic valve replacement from a prospective randomized trial. The observed 20-year overall survival and freedom from aortic valve reoperation serve as a benchmark for future studies on interventions for aortic valve disease in the elderly.     

Surgical resection after neoadjuvant durvalumab and radiation is feasible and safe in non–small cell lung cancer: Results from a randomized trial

ObjectiveSeveral trials have recently reported the safety of pulmonary resection after neoadjuvant immunotherapy with encouraging major pathological response rates. We report the detailed adverse events profile from a recently conducted randomized phase II trial in patients with resectable non–small cell lung cancer treated with neoadjuvant durvalumab alone or with sub-ablative radiation.MethodsWe conducted a randomized phase II trial in patients with non–small cell lung cancer clinical stages I to IIIA who were randomly assigned to receive neoadjuvant durvalumab alone or with sub-ablative radiation (8Gyx3). Secondary end points included the safety of 2 cycles of preoperative durvalumab with and without radiation followed by pulmonary resection. Postoperative adverse events within 30 days were recorded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0).ResultsSixty patients were enrolled and randomly assigned, with planned resection performed in 26 patients in each arm. Baseline demographics and clinical variables were balanced between groups. The median operative time was similar between arms: 128 minutes (97-201) versus 146 minutes (109-214) (P = .314). There was no 30- or 90-day mortality. Grade 3/4 adverse events occurred in 10 of 26 patients (38%) after monotherapy and in 10 of 26 patients (38%) after dual therapy. Anemia requiring transfusion and hypotension were the 2 most common adverse events. The median length of stay was similar between arms (5 days vs 4 days, P = .172).ConclusionsIn this randomized trial, the addition of sub-ablative focal radiation to durvalumab in the neoadjuvant setting was not associated with increased mortality or morbidity compared with neoadjuvant durvalumab alone.     

Surgeon vs Pathologist for Prediction of Pancreatic Fistula: Results from the Randomized Multicenter RECOPANC Study

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Long-term tracing and staining of carbon nanoparticles for axillary lymph nodes in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy

BackgroundThe regression of positive nodes in breast cancer after neoadjuvant chemotherapy (NAC) remains unknown. This study aimed to investigate this regression by injecting and tracing carbon nanoparticles (CNs) into the fusion node prior to NAC in patients with breast cancer.MethodsGuided by ultrasound, 0.3 mL of CNs suspension was injected in the fusion node prior to NAC in 110 patients with local advanced breast cancer. Then the patients underwent breast surgery and total axillary lymph node dissection following 2–6 cycles of NAC. The distribution by intercostobrachial nerves (ICBN) of positive nodes and black-stained nodes was researched, and the relationship between the distribution and lymphovascular invasion were investigated by response to NAC.ResultsWhen patients were ranked by response to NAC (from sensitive to resistance), the number of positive nodes increased, as did the proportion of lymphovascular invasion, the number of black-stained nodes decreased. A significantly negative relationship was found between the number of positive nodes and the number of black-stained nodes (p < 0.001). The positive nodes in patients with sensitive consequence followed the rule from under the ICBN to above the ICBN. However, there was counter-example (skip metastasis) in the patients with resistance result.ConclusionThe regression of positive nodes follows the rule from upper to under, inner to outer in the patients with sensitive consequence to NAC. Long-term staining and tracing by CNs might provide an acceptable and feasible technique to investigate the regression of positive nodes, and would be a potential method for NAC-treated patients by using of ICBN.Trial registrationNCT 03355261. Retrospectively registered on November 28, 2017.     

Validation of a prognostic scoring system for postmastectomy locoregional recurrence in breast cancer

BackgroundTo date, it remains unclear which patients with breast cancer (BC) benefit from post-mastectomy radiotherapy (PMRT). Cheng et al. developed and validated a scoring system based on 4 prognostic factors for locoregional recurrence (LRR) to identify patients in need for PMRT. These factors include age, estrogen receptor status, lymphovascular status and number of affected axillary lymph nodes.PurposeTo validate the scoring system for LRR in BC developed by Cheng et al. by using an independent BC database.Methods and materialsWe retrospectively identified 1989 BC cases, treated with mastectomy (ME) with or without PMRT at the University Hospitals Leuven between 2000 and 2007. The primary endpoint was 5-year locoregional control rate with and without PMRT, according to the LRR score.ResultsMedian follow-up time was 11.4 years. After excluding patients with missing variables 1103 patients were classified using the LRR scoring system: 688 (62.38%) patients were at low risk of recurrence (LRR score 0–1), 335 (30.37%) patients were at intermediate risk of recurrence (LRR score 2–3) and 80 (7.25%) patients were at high risk of recurrence (LRR score ≥4). 5-year locoregional control rates with and without PMRT were 99.20% versus 99.21% (p = 0.43) in the low-risk group; 98.24% versus 85.74% (p < 0.0001) in the intermediate-risk group and 96.87% versus 85.71% (p = 0.10) in the high-risk group respectively.ConclusionOur validation of the LRR scoring system suggests it can be used to point out patients that would benefit from PMRT. We recommend further validation of this scoring system by other independent institutions before application in clinical practice.     

Outcomes after sublobar resection versus lobectomy in non–small cell carcinoma in situ

ObjectiveGuidelines for treatment of non–small cell lung cancer identify patients with tumors ≤2 cm and pure carcinoma in situ histology as candidates for sublobar resection. Although the merits of lobectomy, sublobar resection, and lymphoid (LN) sampling, have been investigated in early-stage non–small cell lung cancer, evaluation of these modalities in patients with IS disease can provide meaningful clinical information. This study aims to compare these operations and their relationship with regional LN sampling in this population.MethodsThe National Cancer Database was used to identify patients diagnosed with non–small cell lung cancer clinical Tis N0 M0 with a tumor size ≤2 cm from 2004 to 2017. The χ² tests were used to examine subgroup differences by type of surgery. Kaplan-Meier method and Cox proportional hazard model were used to compare overall survival.ResultsOf 707 patients, 56.7% (401 out of 707) underwent sublobar resection and 43.3% (306 out of 707) underwent lobectomy. There was no difference in 5-year overall survival in the sublobar resection group (85.1%) compared with the lobectomy group (88.9%; P = .341). Multivariable survival analyses showed no difference in overall survival (hazard ratio, 1.044; P = .885) in the treatment groups. LN sampling was performed in 50.9% of patients treated with sublobar resection. In this group, LN sampling was not associated with improved survival (84.9% vs 85.0%; P = .741).ConclusionsWe observed no difference in overall survival between sublobar resection and lobectomy in patients with cTis N0 M0 non–small cell lung cancer with tumors ≤2 cm. Sublobar resection may be an appropriate surgical option for this population. LN sampling was not associated with improved survival in patients treated with sublobar resection.     

Surgical results of the Lung Cancer Mutation Consortium 3 trial: A phase II multicenter single-arm study to investigate the efficacy and safety of atezolizumab as neoadjuvant therapy in patients with stages IB-select IIIB resectable non–small cell lung cancer

ObjectiveMultimodality treatment for resectable non–small cell lung cancer has long remained at a therapeutic plateau. Immune checkpoint inhibitors are highly effective in advanced non–small cell lung cancer and promising preoperatively in small clinical trials for resectable non–small cell lung cancer. This large multicenter trial tested the safety and efficacy of neoadjuvant atezolizumab and surgery.MethodsPatients with stage IB to select IIIB resectable non–small cell lung cancer and Eastern Cooperative Oncology Group performance status 0/1 were eligible. Patients received atezolizumab 1200 mg intravenously every 3 weeks for 2 cycles or less followed by resection. The primary end point was major pathological response in patients without EGFR/ALK+ alterations. Pre- and post-treatment computed tomography, positron emission tomography, pulmonary function tests, and biospecimens were obtained. Adverse events were recorded by Common Terminology Criteria for Adverse Events v.4.0.ResultsFrom April 2017 to February 2020, 181 patients were entered in the study. Baseline characteristics were mean age, 65.1 years; female, 93 of 181 (51%); nonsquamous histology, 112 of 181 (62%); and clinical stages IIB to IIIB, 147 of 181 (81%). In patients without EGFR/ALK alterations who underwent surgery, the major pathological response rate was 20% (29/143; 95% confidence interval, 14-28) and the pathological complete response rate was 6% (8/143; 95% confidence interval, 2-11). There were no grade 4/5 treatment-related adverse events preoperatively. Of 159 patients (87.8%) undergoing surgery, 145 (91%) had pathologic complete resection. There were 5 (3%) intraoperative complications, no intraoperative deaths, and 2 postoperative deaths within 90 days, 1 treatment related. Median disease-free and overall survival have not been reached.ConclusionsNeoadjuvant atezolizumab in resectable stage IB to IIIB non–small cell lung cancer was well tolerated, yielded a 20% major pathological response rate, and allowed safe, complete surgical resection. These results strongly support the further development of immune checkpoint inhibitors as preoperative therapy in locally advanced non–small cell lung cancer.     

Gefitinib as neoadjuvant therapy for resectable stage II-IIIA non–small cell lung cancer: A phase II study

IntroductionCurrently, limited data on tyrosine kinase inhibitors as neoadjuvant therapy exist. This prospective study aimed to investigate the efficacy and safety of preoperative gefitinib in patients with stage II-IIIA operable non–small cell lung cancer (NSCLC).MethodsThis was a single-arm, phase II trial performed in the Shanghai Cancer Center. Between August 2013 and October 2015, patients with operable stage II-IIIA NSCLC with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R mutation were enrolled. Patients were treated with preoperative gefitinib (250 mg once daily for 42 days), followed by surgical resection. The primary endpoint was objective response rate (ORR); secondary endpoints were the rate of major pathologic response (MPR), disease-free survival (DFS), overall survival, and adverse events (AEs). ORR was defined as the proportion of patients achieving complete response or partial response radiologically. MPR was defined as no more than 10% viable tumor.ResultsOf the 35 eligible patients, 33 were considered as intention-to-treat population. ORR, the primary endpoint, was 54.5% (95% confidence interval [CI], 37.7-70.7), and the rate of MPR was 24.2% (95% CI, 11.9-40.4). Median DFS was 33.5 months (95% CI, 19.7-47.3); median overall survival was not reached. Skin toxicity (24/35,68.6%) and gastrointestinal symptoms (17/35,48.6%) were the most common AEs; no patients reported grade 3 or 4 AEs. After surgery, 4 patients experienced chylothorax (4/33,12.1%). Patients with MPR had a prolonged survival compared with those without (DFS, P = .019).ConclusionsNeoadjuvant therapy with gefitinib in patients with stage II-IIIA NSCLC is safe and may be a viable treatment for patients whose tumors have EGFR mutations. Patients with MPR were associated with improved survival.     

Resection of Colorectal Liver Metastasis: Prognostic Impact of Tumor Burden vs KRAS Mutational Status

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Ketorolac use and anastomotic leak in patients with esophageal cancer

ObjectivesRecent evidence has shown an association between postoperative ketorolac use and anastomotic leak in patients undergoing intestinal and colorectal operations, but this relationship has been minimally explored after esophagectomy. As the use of nonopioid pain control and enhanced recovery protocols is increasingly prioritized, determination of a possible correlation between perioperative ketorolac use and leak is essential.MethodsRecords of patients undergoing esophagectomy for adenocarcinoma at a single institution from 2006 to 2018 reviewed for occurrence of anastomotic leak. Institutional pharmacy records were queried for ketorolac administration during the surgical case through the time of discharge. Multivariable logistic regression was used to determine the relationship between ketorolac administration and anastomotic leak.ResultsA total of 1019 patients met inclusion criteria, the majority of whom were male (907, 89%) with a median age of 62 years. Patients predominantly presented with locoregionally advanced disease and were treated with initial chemoradiation. Ketorolac was administered to 686 patients (67%); use was observed to increase over the study period from 49% in 2006 to 92% in 2016. Conversely, anastomotic leak occurred in 87 patients (9%) overall and decreased over time from 15% (11/72) in 2006 to 2% (2/83) in 2018. Upon multivariable analysis, neither ketorolac administration evaluated as a categoric variable (odds ratio, 0.99; P = .958) or as a continuous variable using dose (odds ratio, 1.00; P = .843) demonstrated an association with anastomotic leak.ConclusionsKetorolac in the postoperative period after esophagectomy has become an integral component of enhanced recovery pathways and does not appear to be associated with anastomotic leak.     

Effect of multidisciplinary team care on the risk of recurrence in breast cancer patients: A national matched cohort study

BackgroundCancer has been the leading cause of death in the past decade in Taiwan, with breast cancer being the most common type of cancer in females. Very few studies looked at the risk of recurrence in patients who received multidisciplinary team (MDT) care. We analyzed the influence of MDT on the risk of recurrence and death in breast cancer patients.MethodIn this retrospective study, we included newly diagnosed patients from 2004 to 2010. The study included 9,266 breast cancer patients who were enrolled in MDT care and 9,266 patients who were not. The study used log-rank test to analyze patients’ characteristics, hospital characteristics, cancer staging, and treatment methods to compare the recurrence rates in MDT care and non-MDT care participants. We used Cox proportional hazards model to examine the effect of MDT and associated factors on the risk of recurrence and mortality of breast cancer patients.ResultsRelative risk of recurrence was lower for patients who received MDT care than for patients who did not (HR, 0.84; 95%CI: 0.70–0.99) after matching. The mortality risk for breast cancer patients with relapse was 8.48 times (95%CI: 7.53–9.54) than that for patients without relapse.ConclusionsThe relative risk of recurrence and death was significantly lower for breast cancer patients who received MDT care than for those who did not. We suggest that MDT care be implanted in the National Health Policy settings of breast cancer patients.     

Association between preoperative prealbumin level and postoperative mortality and morbidity after hepatic resection for hepatocellular carcinoma: A multicenter study from a HBV-endemic area

BackgroundPrealbumin is a more sensitive serum biomarker in reflecting liver function and nutritional status than albumin, because of its shorter half-life and its characteristics that could hardly be affected by supplemental venous infusion of albumin or blood transfusion. This study aimed to identify whether preoperative prealbumin level was associated with postoperative mortality and morbidity after hepatic resection for patients with hepatocellular carcinoma (HCC).MethodsFrom a Chinese multicenter database, patients who underwent hepatic resection for HCC were divided into the low and normal prealbumin groups by using 17 mg/dL as the cut-off level for serum prealbumin taken within a week before surgery. Using univariable and multivariable logistic regression analyses, independent predictors associated with postoperative 30-day and 90-day mortality, 30-day overall and major morbidity, and postoperative hepatic insufficiency were identified.ResultsAmong 1356 patients, 409 (30.2%) had a low preoperative prealbumin level. Postoperative 30-day and 90-day mortality, and 30-day overall and major morbidity in the low prealbumin group were significantly higher than the normal prealbumin group (2.9% vs. 0.5%, 5.1% vs. 1.5%, 35.7% vs. 18.4%, and 14.4% vs. 6.5%, respectively, all P < 0.001). Multivariable analyses identified that preoperative prealbumin level, but not albumin level, was independently associated with postoperative 30-day mortality (OR: 3.486, 95% CI: 1.184–10.265), 90-day mortality (2.504, 1.219–5.145), 30-day overall morbidity (1.727, 1.302–2.292), 30-day major morbidity (1.770, 1.155–2.711) and postoperative hepatic insufficiency (1.967, 1.119–3.427).ConclusionsPreoperative prealbumin level could be used to predict postoperative morbidity and mortality for patients treated with hepatic resection for HCC.     

Lower airway bacterial microbiome may influence recurrence after resection of early-stage non–small cell lung cancer

ObjectiveThe lower airway bacterial microbiome influences carcinogenesis and response to immunotherapy in non–small cell lung cancer (NSCLC). We investigated the association of this microbiome with recurrence in early NSCLC.MethodsMicrobiomes of presurgery bronchoalveolar lavage (BAL) and saliva, and resected stage I NSCLC tumor and adjacent lung tissues of 48 patients were examined by 16S gene sequencing. Tumor gene expression was measured by RNA sequencing.ResultsSpatial relationships of the different biospecimen types was reflected in their microbiomes, with microbiomes of BAL intermediate to those of saliva and lung tissue. BAL and saliva microbiomes were less dissimilar in patients with high α-amylase levels in BAL, indicating oral aspiration as a source of lower airway microbiota. BAL microbiomes of patients with recurrence within 32 months of surgery differed from those without recurrence during ≥32 months of follow-up (n = 18 each), despite no difference for age, sex, smoking history, and tumor histology and grade. The recurrence-associated BAL microbiome signature was present in 16 of the 18 recurrence cases but in only two of the others. Signature presence was associated with shorter recurrence-free survival (log-rank test P < .001; hazard ratio = 14.5), and greater expression in tumors of genes for cell proliferation and epithelial mesenchymal transition. Immune cellular composition of the tumor microenvironment was not different between patients with and without the signature.ConclusionsPresurgery composition of lower airway microbiome may be associated with recurrence of early NSCLC. This association may reflect an influence of the microbiome on tumor biology.     

Prognostic factors for progression-free survival of the filum terminale ependymomas in adults

ObjectiveTo define the prognostic factors for progression and to determine the impact of the histological grading (according to the World Health Organization) on the progression-free survival (PFS) of filum terminale ependymomas.MethodsA retrospective chart review of 38 patients with ependymoma of the filum terminale was performed, focusing on demographic data, preoperative symptoms, tumor size, quality of resection, presence of a tumor capsule, and histological grade.ResultsGross total resection (GTR) was achieved in 30 patients (78.9%). Histopathological analysis found 21 (55.3%) myxopapillary grade I ependymoma (MPE), 16 (42.1%) ependymoma grade II (EGII), and 1 (2.6%) ependymoma grade III. There was no significant difference between the mean ± SD volume of MPE (5840.5 ± 5244.2 mm³) and the one of EGII (7220.3 ± 6305.9 mm³, p = 0.5). The mean ± SD follow-up was 54.1 ± 38.4 months. At last follow-up, 30 (78.9%) patients were free of progression. In multivariate analysis, subtotal resection (p = 0.015) and infiltrative tumor (p = 0.03) were significantly associated with progression. The PFS was significantly higher in patients with encapsulated tumor than in patients with infiltrative tumor (log-rank p = 0.01) and in patients who had a GTR in comparison with those who had an incomplete resection (log-rank p = 0.05). There was no difference in PFS between patient with MPE and EGII (p = 0.1).ConclusionThe progression of ependymoma of the filum terminale highly depends on the quality of resection, and whether the tumor is encapsulated. Except for anaplastic grade, histopathological type does not influence progression.