Survival in Women with De Novo Metastatic Breast Cancer: A Comparison of Real-World Evidence from a Publicly-Funded Canadian Province and the United States by Insurance Status

Metastatic breast cancer (MBC) patient outcomes may vary according to distinct health care payers and different countries. We compared 291 Alberta (AB), Canada and 9429 US patients < 65 with de novo MBC diagnosed from 2010 through 2014. Data were extracted from the provincial Breast Data Mart and from the National Cancer Institute’s SEER program. US patients were divided by insurance status (US privately insured, US Medicaid or US uninsured). Kaplan-Meier and log-rank analyses were used to assess differences in OS and hazard ratios (HR) were estimated using Cox models. Multivariate models were adjusted for age, surgical status, and biomarker profile. No difference in OS was noted between AB and US patients (HR = 0.92 (0.77–1.10), p = 0.365). Median OS was not reached for the US privately insured and AB groups, and was 11 months and 8 months for the US Medicaid and US uninsured groups, respectively. The 3-year OS rates were comparable between US privately insured and AB groups (53.28% (51.95–54.59) and 55.54% (49.49–61.16), respectively). Both groups had improved survival (p < 0.001) relative to the US Medicaid and US uninsured groups [39.32% (37.25–41.37) and 40.53% (36.20–44.81)]. Our study suggests that a universal health care system is not inferior to a private insurance-based model for de novo MBC.

Diagnostic and Therapeutic Challenges in a Patient with Synchronous Very High-Risk Prostate Adenocarcinoma and Anal Carcinoma

A 79-year-old HIV-negative Caucasian man with a medical history of smoking 20 pack-years (quit 40 years prior), early-stage non-small cell lung cancer status post-lobectomy 13 years earlier at an outside hospital without evidence of recurrence, and benign prostatic hypertrophy was diagnosed with synchronous very high-risk prostate adenocarcinoma and early-stage anal basaloid squamous cell carcinoma. He proceeded to undergo concurrent treatment for these tumors, consisting of androgen deprivation therapy, external beam radiation therapy, and a brachytherapy boost for the prostate adenocarcinoma; for the anal carcinoma, he was treated with definitive chemoradiation. Over 3.5 years since the completion of radiotherapy, he remains in clinical and biochemical remission.

Treatment of Older Adult Patients with Glioblastoma: Moving towards the Inclusion of a Comprehensive Geriatric Assessment for Guiding Management

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, and over half of patients with newly diagnosed GBM are over the age of 65. Management of glioblastoma in older patients includes maximal safe resection followed by either radiation, chemotherapy, or combined modality treatment. Despite recent advances in the treatment of older patients with GBM, survival is still only approximately 9 months compared to approximately 15 months for the general adult population, suggesting that further research is required to optimize management in the older population. The Comprehensive Geriatric Assessment (CGA) has been shown to have a prognostic and predictive role in the management of older patients with other cancers, and domains of the CGA have demonstrated an association with outcomes in GBM in retrospective studies. Furthermore, the CGA and other geriatric assessment tools are now starting to be prospectively investigated in older GBM populations. This review aims to outline current treatment strategies for older patients with GBM, explore the rationale for inclusion of geriatric assessment in GBM management, and highlight recent data investigating its implementation into practice.

A Portrait of SARS-CoV-2 Infection in Patients Undergoing Hematopoietic Cell Transplantation: A Systematic Review of the Literature

The management of COVID-19 in hematopoietic cell transplant (HCT) recipients represents a special challenge given the variable states of immune dysregulation and altered vaccine efficacy in this population. A systematic search (Ovid Medline and Embase on 1 June 2021) was needed to better understand the presenting features, prognostic factors, and treatment options. Of 897 records, 29 studies were identified in our search. Most studies reporting on adults and pediatric recipients described signs and symptoms that were typical of COVID-19. Overall, the mortality rates were high, with 21% of adults and 6% of pediatric HCT recipients succumbing to COVID-19. The factors reported to be associated with increased mortality included age (HR = 1.21, 95% CI 1.03–1.43, p = 0.02), ICU admission (HR = 4.42, 95% CI 2.25–8.65, p < 0.001 and HR = 2.26, 95% CI 1.22–4.20, p = 0.01 for allogeneic and autologous HCT recipients), and low platelet count (OR = 21.37, 95% CI 1.71–267.11, p = 0.01). Performance status was associated with decreased mortality (HR = 0.83, 95% CI 0.74–0.93, p = 0.001). A broad range of treatments was described, although no controlled studies were identified. The risk of bias, using the Newcastle–Ottawa scale, was low. Patients undergoing HCT are at a high risk of severe morbidity and mortality associated with COVID-19. Controlled studies investigating potential treatments are required to determine the efficacy and safety in this population.

Safety Profile of Niraparib as Maintenance Therapy for Ovarian Cancer: A Systematic Review and Meta-Analysis

Background: Patients with epithelial ovarian cancer (EOC), treated with niraparib maintenance, present with haematological and gastrointestinal toxicities. Limited data exist on niraparib safety assessment. Objective: To evaluate niraparib safety profile, as maintenance therapy, in women with platinum-sensitive EOC. Methods: PubMed and Cochrane searches were carried out up to April 2021 for randomised controlled trials (RCTs) evaluating niraparib versus placebo in EOC patients with a response to platinum-based chemotherapy. Regarding the meta-analysis, for dichotomous data, the pooled risk ratio (RR) was calculated. Results: A total of 1539 patients from three RCTs revealed that niraparib-treated patients are associated with a significantly higher risk of any grade of nausea (RR, 2.15; 95% CI, 1.86 to 2.48), fatigue (RR, 1.26; 95% CI, 1.05 to 1.52, p < 0.00001), anemia (RR, 6.86; 95% CI, 2.54 to 18.52, p = 0.0001), thrombocytopenia (RR, 7.02; 95% CI, 1.68 to 29.38, p < 0.00001), vomiting (RR, 2.51; 95% CI, 1.50 to 4.19, p = 0.0005), neutropenia (RR, 2.96; 95% CI, 1.13 to 7.73, p < 0.00001), headache (RR, 2.08; 95% CI, 1.57 to 2.74, p < 0.00001), constipation (RR, 2.10; 95% CI, 1.72 to 2.57, p < 0.00001) and insomnia (RR, 2.48; 95% CI, 1.52 to 2.89, p = 0.0003) when compared with placebo. For grade 3 or 4 adverse effects, significantly higher risk was only noted for fatigue (RR,6.25; 95% CI, 1.70 to 23.05, p = 0.006), anemia (RR, 16.23; 95% CI, 4.86 to 54.17, p < 0.00001), thrombocytopenia (RR, 35.12; 95% CI, 12.23 to 100.82, p < 0.00001) and neutropenia episodes (RR, 6.35; 95% CI, 2.08 to 19.39, p = 0.001) for those taking niraparib. Notably, incidents of adverse effects and discontinuation rates were substantially lower among patients treated with an individualised niraparib dose than those treated with the standard one. Efficacy was not reduced, and no treatment-related deaths occurred during the included trials. Conclusion: Niraparib is considered an effective and well-tolerated choice, with an improved safety profile, for the maintenance treatment of EOC patients.

Upfront Chemotherapy Followed by Stereotactic Body Radiation Therapy with or without Surgery in Older Patients with Localized Pancreatic Cancer: A Single Institution Experience and Review of the Literature

Objective: To report on clinical outcomes and toxicity in older (age ≥ 70 years) patients with localized pancreatic cancer treated with upfront chemotherapy followed by stereotactic body radiation therapy (SBRT) with or without surgery. Methods: Endpoints included overall survival (OS), local progression-free survival (LPFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and toxicity. Results: A total of 57 older patients were included in the study. Median OS was 19.6 months, with six-month, one-year, and two-year OS rates of 83.4, 66.5, and 42.4%. On MVA, resection status (HR: 0.30, 95% CI 0.12–0.91, p = 0.031) was associated with OS. Patients with surgically resected tumors had improved median OS (29.1 vs. 7.0 months, p < 0.001). On MVA, resection status (HR: 0.40, 95% CI 0.17–0.93, p = 0.034) was also associated with PFS. Patients with surgically resected tumors had improved median PFS (12.9 vs. 1.6 months, p < 0.001). There were 3/57 cases (5.3%) of late grade 3 radiation toxicity and 2/38 cases (5.3%) of Clavien-Dindo grade 3b toxicity in those who underwent resection. Conclusion: Multimodality therapy involving SBRT is safe and feasible in older patients with localized pancreatic cancer. Surgical resection was associated with improved clinical outcomes. As such, older patients who complete chemotherapy should not be excluded from aggressive local therapy when possible.

Immune Effective Score as a Predictor of Response to Neoadjuvant Trastuzumab Therapy and a Prognostic Indicator for HER2-Positive Breast Cancer

Background: HER2-positive breast cancer (BC) is a highly aggressive phenotype. The role of the host immune features in predictive response to anti-HER2 therapies and prognosis in BC has already been suggested. We aimed to develop a predictive and prognostic model and examine its relevance to the clinical outcomes of patients with HER2-positive BC. Methods: Immune effective score (IES) was constructed using principal component analysis algorithms. A bioinformatic analysis using four independent cohorts (GSE66305, n = 88; GSE130786, n = 110; TCGA, n = 123; METABRIC, n = 236) established associations between IES and clinical outcomes. Results: Genes associated with neoadjuvant trastuzumab therapy response were enriched in pathways related to antitumor immune activities. IES was demonstrated to be a predictive biomarker to neoadjuvant trastuzumab therapy benefits (GSE66305: area under the curve (AUC) = 0.804; GSE130786: AUC = 0.704). In addition, IES was identified as an independent prognostic factor for overall survival (OS) in the TCGA cohort (p = 0.036, hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.449–0.97) and METABRIC cohort (p = 0.037, HR: 0.9, 95% CI: 0.81–0.99). Conclusion: IES has a predictive value for response to neoadjuvant trastuzumab therapy and independent prognostic value for HER2-positive breast cancer.

Lymph Node Dissection Is a Risk Factor for Short-Term Cough after Pulmonary Resection

Cough is a common complication after pulmonary resection. However, the factors associated with cough that develop after pulmonary resection are still controversial. In this study, we used the Simplified Cough Score (SCS) and the Leicester Cough Questionnaire (LCQ) score to investigate potential risk factors for postoperative cough. Between January 2017 and June 2021, we collected the clinical data of 517 patients, the SCS at three days after surgery and the LCQ at two weeks and six weeks after surgery. Then, univariate and multivariate analyses were used to identify the independent risk factors for postoperative cough. The clinical baseline data of the cough group and the non-cough group were similar. However, the cough group had longer operation time and more blood loss. The patients who underwent lobectomy were more likely to develop postoperative cough than the patients who underwent segmentectomy and wedge resection, while the patients who underwent systematic lymph node dissection were more likely to develop postoperative cough than the patients who underwent lymph node sampling and those who did not undergo lymph node resection. When the same lymph node management method was applied, there was no difference in the LCQ scores between the patients who underwent wedge resection, lobectomy and segmentectomy. The lymph node resection method was an independent risk factor for postoperative cough (p < 0.001). Conclusions: Lymph node resection is an independent risk factor for short-term cough after pulmonary resection with video-assisted thoracoscopic surgery, and damage to the vagus nerve and its branches (particularly the pulmonary branches) is a possible cause of short-term cough. The mechanism of postoperative cough remains to be further studied.

Uncommon EGFR Compound Mutations in Non-Small Cell Lung Cancer (NSCLC): A Systematic Review of Available Evidence

Compound epidermal growth factor receptor (EGFR) mutations represent a heterogeneous subgroup of non-small cell lung cancer (NSCLC) patients with uncommon EGFR mutations. We conducted a systematic review to investigate the available data on this patients’ subgroup. Overall, we found a high heterogeneity in the incidence of compound mutations (4–26% of total EGFR mutant cases), which is dependent on the different testing methods adopted and the specific mutations considered. In addition, the relative incidence of distinct compound subclasses identified is reported with extreme variability in different studies. Preclinical and clinical data, excluding de novoEGFR exon 20 p.T790M compound mutations, show good responses with EGFR tyrosine kinase inhibitors (TKIs) (combined common mutations: response rate (RR) ≥ 75% with either first- or second-generation TKIs; combined common plus uncommon: RR 40–80% and 100% with first-generation TKIs and afatinib, respectively; combined uncommon: RR 20–70%, ~80% and ~75% with first-generation TKIs, afatinib and osimertinib, respectively). Overall, data are consistent in supporting the use of EGFR TKIs in treating compound EGFR mutations, taking into account different sensitivity profile of accompanying EGFR mutations for selecting the most adequate EGFR TKI for individual patients.

Immune-Related Pneumonitis Was Decreased by Addition of Chemotherapy with PD-1/L1 Inhibitors: Systematic Review and Network Meta-Analysis of Randomized Controlled Trials (RCTs)

Purpose: Immune-related pneumonitis (IRP) has attracted extensive attention, owing to its increased mortality rate. Conventional chemotherapy (C) has been considered as an immunosuppressive agent and may thus reduce IRP’s risk when used in combination with PD-1/L1 inhibitors. This study aimed to assess the risk of IRP with PD-1/L1 inhibitors plus chemotherapy (I+C) versus PD-1/L1 inhibitors alone (I) in solid cancer treatment. Method: Multiple databases were searched for RCTs before January 2021. This NMA was performed among I+C, I, and C to investigate IRP’s risk. Subgroup analysis was carried out on the basis of different PD-1/L1 inhibitors and cancer types. Results: Thirty-one RCTs (19,624 patients) were included. The I+C group exhibited a lower risk of IRP in any grade (RR, 0.60; 95% CI, 0.38–0.95) and in grade 3–5 (RR, 0.42; 95% CI, 0.21–0.92) as opposed to the I group. The risk of any grade IRP with PD-1 plus chemotherapy was lower than that with PD-1 monotherapy (RR, 0.50; 95% CI, 0.28–0.89), although grade 3–5 IRP was similar. There was no statistically meaningful difference in the risk of any grade IRP between PD-L1 plus chemotherapy and PD-L1 inhibitors monotherapy (RR, 0.95; 95% CI, 0.43–2.09) or grade 3–5 IRP (RR, 0.71;95% CI, 0.24–2.07). In addition, compared with the I group, the I+C group was correlated with a decreased risk in IRP regardless of cancer type, while a substantial difference was only observed in NSCLC patients for grade 3–5 IRP (RR, 0.39; 95% CI, 0.15–0.98). Conclusion: In comparison to PD-1/L1 inhibitor treatment alone, combining chemotherapy with PD-1/L1 inhibitors might reduce the risk of IRP in the general population. Furthermore, PD-1 inhibitors in combination with chemotherapy were correlated with a decreased risk of IRP compared to PD-1 inhibitor treatment alone. In contrast to the I group, the I+C group exhibited a lower risk of IRP, especially for NSCLC patients.