Curr. Oncol., Volume 29, Issue 11 (November 2022) – 76 articles

Background: Neuroendocrine neoplasms (NENs) are a heterogeneous group of cancers that had a significant increase in annual incidence in the last decade. They can be divided into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Poorly differentiated NECs are aggressive forms of cancers with limited therapeutic options. The first line treatment of metastatic poorly differentiated NECs is similar to small cell lung cancer, with cytotoxic chemotherapy (etoposide plus platinum). Patients who progress have limited therapeutic options and poor overall survival, calling for other novel agents to combat this deadly disease. Therefore, in this article, we summarized the effects of a novel component, Thymoquinone (TQ, C10H12O2), which is the main bioactive component of the black seed (Nigella sativa, Ranunculaceae family), plus immunotherapy in case series of patients with refractory metastatic extra-pulmonary NEC (EP-NEC) and one case of mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN). Methods: We report the effect of TQ plus dual immune checkpoint inhibitors (nivolumab plus ipilimumab) in four patients with poorly differentiated gastrointestinal Ep-NEC and MiNEN who progressed on cytotoxic chemotherapy. Results: This is the first case series to report the clinical activity of TQ plus dual immune checkpoint inhibitors (nivolumab plus ipilimumab) in patients with refractory metastatic EP-NEC. The four patients showed benefits with the combined regimen TQ plus dual ICPIs with durable response and exceeded the two years of progression-free survival. None of the four patients experienced significant toxicity, and all of them showed improvement in quality of life. Conclusion: The reported clinical courses suggest that combined TQ plus ICPIs is a potential promising regimen for refractory EP-NEC and MiNEN that deserves further prospective investigation. Full article

Background: Serum lipids (SLs), the prominent indicators of lipid metabolism, produce an intricate impact on proliferation, invasion, and metastasis of cancer cells. However, the effects of serum lipids on the prognosis of ampullary adenocarcinoma (AC) have not been investigated. Methods: Patients with AC in the National Cancer Center of China between January 1998 and December 2020 were retrospectively reviewed. Survival analysis for overall survival (OS, Time from operation to death) and recurrence-free survival (RFS, Time from operation to first-time recurrence) was performed using Kaplan–Meier analysis and Cox proportional hazards models. Results: A total of 232 AC patients were enrolled into the study. SLs levels were significantly lower in patients with vascular invasion compared to those without (all p < 0.05). The 1-year, 3-year, and 5-year OS rates for AC patients were 86.1%, 64.1%, and 47.6% and 75.8%, 54.8%, and 46.5% for RFS. Biliary/pancreatic fistula (31.9%) and chemotherapy (81.4%) were the majority of postoperative complications and adjuvant therapy, respectively. According to Cox analysis, preoperative LDL-C was an independent prognostic factor for RFS (HR = 0.43, 95% CI: 0.21–0.85, p = 0.015), whereas no statistical significance existed in the analysis of HDL-C, TC, and TG. Conclusions: High levels of preoperative LDL-C is a significant predictor of prolonged prognosis in AC patients, which was also observed to be a protective factor to reduce vascular invasion. Full article

The treatment landscape of multiple myeloma (MM) has evolved considerably with the FDA-approval of at least 15 drugs over the past two decades. Together with the use of autologous stem cell transplantation, these novel therapies have resulted in significant survival benefit for patients with MM. In particular, our improved understanding of the BM and immune microenvironment has led to the development of highly effective immunotherapies that have demonstrated unprecedented response rates even in the multiple refractory disease setting. However, MM remains challenging to treat especially in a high-risk setting. A key mediator of therapeutic resistance in MM is the bone marrow (BM) microenvironment; a deeper understanding is necessary to facilitate the development of therapies that target MM in the context of the BM milieu to elicit deeper and more durable responses with the ultimate goal of long-term control or a cure of MM. In this review, we discuss our current understanding of the role the BM microenvironment plays in MM pathogenesis, with a focus on its immunosuppressive nature. We also review FDA-approved immunotherapies currently in clinical use and highlight promising immunotherapeutic approaches on the horizon. Full article

Distance caregivers (DCGs), those who live more than an hour away from the care recipient, often play a significant role in patients’ care. While much is known about the experience and outcomes of local family caregivers of cancer patients, little is known about the experience and outcomes of distance caregiving upon DCGs. The purpose of this study was to identify the relationships among stressors (patient cancer stage, anxiety, and depression), mediators (DCG emotional support and self-efficacy), and burden in DCGs’ of patients with cancer. This study was a descriptive cross-sectional study and involved a secondary data analysis from a randomized clinical trial. The study sample consisted of 314 cancer patient–DCG dyads. The results of this study were: (1) 26.1% of DCGs reported elevated levels of burden; (2) significant negative relationships were found between mediators (DCG emotional support and self-efficacy) and DCG burden; and (3) significant positive relationships were found between patient anxiety, depression, and DCG burden. The prevalence of burden in DCGs, and its related factors, were similar to those of local caregivers of cancer patients, which suggests that interventions to reduce burden in local caregivers could be effective for DCGs as well. Full article

Colorectal cancer (CRC) is the third most prevalent cancer, and the second most common cancer-related cause of death in the United States (USA). Timely screening reduces both CRC incidence and mortality. Understanding population behaviors and factors that influence CRC screening is important for directing interventions targeted at reducing CRC rates. The 1997–2018 Behavioral Risk Factor Surveillance System (BRFSS) data were analyzed for trends in colonoscopy and sigmoidoscopy utilization for CRC screening among adults in Georgia, USA. Overall, in Georgia, there has been an increase in the prevalence of colonoscopy and sigmoidoscopy utilization from 48.1% in 1997 to 71.2% in 2018 (AAPC = 2.30, p < 0.001). Compared nationally, this increase was less pronounced (from 41.0% in 1997 to 73.7% in 2018 (AAPC = 2.90, p < 0.001) overall for USA). Logistic regression analysis of the 2018 BRFSS data, adjusting for sociodemographic factors, shows that sex (female vs. male [aOR = 1.20, C.I. = 1.05, 1.38]); marital status (couple vs. single [aOR = 1.20, C.I. = 1.04, 1.39]); healthcare coverage (yes vs. no [aOR = 3.86, C.I. = 3.05, 4.88]); age (60–69 years [aOR = 2.38, C.I. = 2.02, 2.80], 70–79 [aOR = 2.88, C.I. = 2.38, 3.48] vs. 50–59 years); education (high school [aOR = 1.32, C.I. = 1.05, 1.65], some post high school [aOR= 1.63, C.I. = 1.29, 2.06], college graduate [aOR = 2.08, C.I. = 1.64, 2.63] vs. less than high school); and income ($25,000–$49,999 [aOR = 1.24, C.I. = 1.01, 1.51], $50,000+ [aOR = 1.56, C.I. = 1.27, 1.91] vs. <$25,000) were all significantly associated with colonoscopy and sigmoidoscopy utilization. In Georgia, a significant increase over time in colonoscopy and sigmoidoscopy utilization for CRC screening was observed pertaining to the associated sociodemographic factors. The findings from this study may help guide tailored programs for promoting screening among underserved populations. Full article

Background. Chemoimmunotherapy has become the first-line treatment for unresectable esophageal squamous cell carcinoma (ESCC). Still, reliable biomarkers to identify patients who could benefit from this combined therapy remain uncertain. This study focused on elucidating the predictive significance of the monocyte-to-lymphocyte ratio (MLR) and establishing the prognostic nomogram for unresectable ESCC treated with chemoimmunotherapy. Methods. Data of clinical features, peripheral blood parameters, and treatment records were collected in unresectable ESCC patients who received PD-1/PD-L1 inhibitors plus chemotherapy as the first-line treatment from September 2017 to August 2021. The nomogram based on MLR and clinical parameters for predicting the overall survival (OS) was developed and validated. Results. Out of 81 patients enrolled, patients with a lower MLR had significantly longer progression-free survival (PFS) and OS than patients with a higher pretreatment MLR (p = 0.0067; p = 0.00069). The OS nomogram integrating MLR, performance status (PS) score, and body mass index (BMI) achieved a C-index of 0.770 (95%CI 0.645–0.896). The area under the ROC curve (AUC) value of the nomogram predicting 12-, 18-, and 24-month OS rates were 0.855, 0.792, and 0.744, respectively, which were higher than the clinical TNM staging system or the MLR. Stratified by the nomogram-generated scores, three risk groups (low, moderate, and high) in survival curves manifested a distinct difference (p < 0.0001). Conclusion. MLR emerged as an independent predictive factor for PFS and OS in treatment-naive unresectable ESCC patients treated with chemoimmunotherapy. The constructed nomogram of MLR and clinical parameters was a reliable model for prognostic estimation. Full article

Background: The novel coronavirus that has triggered the present COVID-19 pandemic continues to spread globally, resulting in widespread morbidity and mortality. Patients with cancer remain one of the most vulnerable subsets of the population to the disease. This study examined the effects of the pandemic on cancer patients’ treatment, psychology, knowledge, attitudes, and practices. Methods: A survey was emailed to 9861 patients at a cancer centre in Toronto, Canada. Descriptive results were summarized. Qualitative feedback was coded and summarized. Regression modelling was used to explore factors associated with patient psychological well-being, knowledge, attitudes, and practices. Results: A total of 1760 surveys were completed, with a response rate of 17.8%. Most participants did not experience any pandemic-related treatment delays, and vaccination rates were high. Participants who identified themselves as non-white (OR 3.30, CI: 1.30–5.30; p ≤ 0.001), and those who referred to journal articles for information (p = 0.002) reported higher psychological impact scores. There were no significant predictors of whether participants would use personal protective equipment when leaving their homes or whether they would go to crowded places. Discussion: This study provides another snapshot of cancer patients perceptions and needs during the COVID-19 pandemic. Full article

This study aimed to explore clinical significance of interleukin-1 receptor-associated kinase 1 (IRAK1) in the diagnosis, prognosis, and targeted therapy of hepatocellular carcinoma. A systematic analysis based on the cancer genome atlas (TCGA) indicated that IRAK1 was highly expressed in 18 cancer types (p < 0.01) and may be a pan-cancer biomarker. In hepatocellular carcinoma, the alteration rate of IRAK1 was rather high (62.4%), in which mRNA high relative to normal predominated (58.9%). Higher expression was associated with shorter overall survival (p < 0.01). IRAK1 expression correlated positively with pathology stage and tumor grade (for the latter there was only a slight trend). Interestingly, it correlated positively with TP53 mutation (p < 0.001), suggesting a possible strategy for targeting TP53 via IRAK1. Immunohistochemistry experiments confirmed a higher positive rate of IRAK1 in carcinoma than in para-carcinoma tissues (χ² = 18.006, p < 0.001). Higher tumor grade correlated with more strongly positive staining. Molecular docking revealed cryptotanshinone, matrine, and harmine as the best hit compounds with inhibition potential for IRAK1. Our findings suggest that IRAK1 may play biologically predictive roles in hepatocellular carcinoma. The suppression of IRAK1/NF-κB signaling via inhibition of IRAK1 by the hit compounds can be a potential strategy for the targeted therapy. Full article

Indoor tanning (sunbeds, solarium) uses artificial ultraviolet radiation (UVR) to stimulate cosmetic tanning of the skin. Indoor tanning has been officially classified as a human carcinogen in 2009 by the International Agency for Research on Cancer of the World Health Organization (WHO). The differences in the prevalence of sunbed use across countries and over the years highlight underlying legislative, climatic, and cultural differences. Indoor tanning-seeking behaviors may be driven by motivations for an appealing appearance, largely influenced by gender and age, and several misconceptions that a prevacation tan safeguards the skin, that sunbeds can be used to treat acne or to increase vitamin D, or that tanning is a healthy habit. This review provides an epidemiological update on the prevalence of sunbed use, who tends to use sunbeds and why, and details the current evidence on the association of sunbeds with skin cancers, including cutaneous melanoma, basal cell carcinoma (BCC), and cutaneous squamous cell carcinoma (cSCC). A statistically significant higher risk of cutaneous melanoma, BCC and cSCC with the use of sunbeds has been consistently demonstrated. This risk of skin cancer is even higher with the more frequent use of sunbeds, underscoring a dose–response relationship, and in those first exposed to sunbeds at a younger age. Preventive measures against sunbed use include legislation restricting sunbed use, educational campaigns to inform and discourage from indoor tanning, as well as using the internet, online advertising messages and the social media to reach larger audiences and to promote an untanned appearance. Full article

Purpose: Surgical interventions tend to have an effect on the generation of recurrences in tumor patients due to the anesthesia involved as well as tissue damage and subsequent inflammation. This can also be found in patients with breast cancer. Methods: In this multicenter study, we investigated data of 632 patients with breast cancer and the subsequent diagnosis of a recurrence. The patient data were acquired from 1 January 2006 to 31 December 2019 in eight different centers in Germany. The data sets were separated into those with primary surgery, primary systemic therapy with subsequent surgery, and reconstructive surgery. Three different starting points for observation were defined: the date of diagnosis, the date of first surgery, and the date of reconstructive surgery, if applicable. The observational period was divided into steps of six months and maxima of recurrences were compared. Furthermore, the variance was calculated using the difference of the distribution in percent. Results: The descriptive analysis showed no resemblance between the groups. The variance of the difference of the recurrence rates analysis using the surgical date as the starting point showed similarities in the age subgroup. Conclusion: Our clinical analysis shows different metastatic behavior in different analysis and treatment regimes. These findings justify further investigations on a larger database. These results may possibly identify an improved follow-up setting depending on tumor stage, biology, treatment, and patient factors (i.e., age, …). Full article

Gastroblastoma is an extremely rare stomach tumor that primarily presents in adolescent and early adulthood, with a biphasic cell morphology of epithelioid and spindle cells. In light of its similarity to other childhood blastomas, it has been named gastroblastoma. Few patients showed a potential of metastasis and recurrence, however, most of the reported cases were alive, with no evidence of the disease after surgical treatment. Commonly, MALAT1-GLI1 fusion has been considered to be the most relevant mutation. Herein, we present a case of an asymptomatic 58-year-old man who happened to find a submucosal gastric mass during a gastroscope and received endoscopic submucosal excavation (ESE). He turned out to have a gastroblastoma with a novel PTCH1::GLI2 fusion confirmed by Sanger sequencing. The patient was discharged two days after ESE without any complication and was recurrence-free during his one-year follow-up. According to the previous literature and our own experience, in cases with characteristic histopathology and immunohistochemistry patterns, a diagnosis of gastroblastoma should be considered even without a MALAT1-GLI1 fusion. Gastroblastoma pursues a favorable clinical outcome and endoscopic therapy could be an effective alternative treatment choice. Full article

Chemotherapy as an adjuvant therapy that has largely failed to significantly improve outcomes for aggressive brain tumors; some reasons include a weak blood brain barrier penetration and tumor heterogeneity. Recently, there has been interest in designing effective ways to deliver chemotherapy to the tumor. In this review, we discuss the mechanisms of focused chemotherapies that are currently under investigation. Nanoparticle delivery demonstrates both a superior permeability and retention. However, thus far, it has not demonstrated a therapeutic efficacy for brain tumors. Convection-enhanced delivery is an invasive, yet versatile method, which appears to have the greatest potential. Other vehicles, such as angiopep-2 decorated gold nanoparticles, polyamidoamine dendrimers, and lipid nanostructures have demonstrated efficacy through sustained release of focused chemotherapy and have either improved cell death or survival in humans or animal models. Finally, focused ultrasound is a safe and effective way to disrupt the blood brain barrier and augment other delivery methods. Clinical trials are currently underway to study the safety and efficacy of these methods in combination with standard of care. Full article

Intraocular lymphoma (IOL) comprises a group of malignant tumours originating from lymphohematopoietic tissues that have a poor prognosis. These tumours predominantly occur in the vitreous and retina but are rarely found in the choroid. A few case reports and case series of choroidal lymphoma (CL) have been reported in the literature. CL is prone to misdiagnosis and incorrect treatment because it often mimics other intraocular diseases such as uveitis. This may seriously affect localisation of the primary lesion and delay treatment, which may even affect the patient’s survival. Herein, we report a case of CL and propose the combination of characteristic ophthalmic imaging with systemic imaging and aqueous humour detection to establish a robust basis for the early diagnosis of CL. Full article

Background: Prognostic factors for poor survival have been proposed in esophageal squamous cell carcinoma (SCC) patients receiving concurrent chemoradiotherapy (CCRT). We conducted a retrospective study on hematological profile after first cycle of chemotherapy for esophageal SCC patients receiving CCRT. Methods: From January 2008 to December 2017, a total of 420 patients with esophageal SCC were enrolled. All included patients had undergone CCRT. Complete blood count, differential count, NLR, and PLR before chemotherapy (CHT) and after first cycle of CHT were obtained. Univariate and multivariate Cox regression analyses were used to assess the association between survival and patient, disease, and treatment characteristics. Results: On univariate analysis, significant factors for overall survival (OS) and disease specific survival (DSS) included ECOG performance status, clinical staging, operation, cisplatin dose, prechemotherapy NLR and PLR, and elevated postchemotherapy NLR. On multivariate analysis, ECOG performance status 0–I, Clinical staging I–II, Operation, cisplatin dose >150 mg/m², prechemotherapy PLR <375, and postchemotherapy platelet count ≥150 × 10⁹/L were independent factors for predicting better OS. Independent factors for predicting better DSS included ECOG performance status 0–I, Clinical staging I–II, Operation, cisplatin dose >150 mg/m², and prechemotherapy PLR <375. Conclusions: Our study showed that low levels of prechemotherapy PLR and NLR were associated with better OS and DSS. Elevated platelet count and NLR after first cycle of CHT were associated with better OS. Elevated PLR and NLR after first cycle of CHT were associated with better DSS. Full article

Hypernatremia (>145 mmol/L) is a relatively rare event, and the data regarding its role in the outcome of inpatients on an oncology ward are weak. The aim of this study was to describe the prevalence, prognosis, and outcome of hospitalized cancer patients with hypernatremia. We performed a retrospective case-control study of data obtained from inpatients with a solid tumor at the St. Claraspital, Basel, Switzerland, who were admitted between 2017 and 2020. The primary endpoint was overall survival. Hypernatremia was found in 93 (3.16%) of 2945 inpatients bearing cancer or lymphoma. From 991 eligible normonatremic control patients, 93 were matched according to diagnosis, age, and sex. The median overall survival time (OS) of patients with hypernatremia was 1.5 months compared to 11.7 months of the normonatremic controls (HR 2.69, 95% CI 1.85–3.90, p < 0.0001). OS of patients with irreversible compared to reversible hypernatremia was significantly shorter (23 versus 88 days, HR 4.0, 95% CI 2.04–7.70, p < 0.0001). The length of hospital stay was significantly longer for the hypernatremic than for the normonatremic group (p < 0.0001). Significantly more patients with hypernatremia died in the hospital (30.1% versus 8.6%, p < 0.001). These results suggest hypernatremia to be associated with an unfavorable outcome and a very short OS. Full article

Background: Hepatocellular carcinoma (HCC) is the most frequent liver malignancy and a leading cause of cancer death in the world. In unresectable HCC patients, transcatheter arterial (chemo-) embolization (TAE/TACE) has shown a disease response in 15–55% of cases. Though multiple TAE/TACE courses can be administered in principle, Stereotactic Body Radiotherapy (SBRT) has emerged as an alternative option in the case of local relapse following multiple TAE/TACE courses. Methods: This is a single-center, prospective, randomized, controlled, parallel-group superiority trial of SBRT versus standard TAE/TACE for the curative treatment of the intermediate stage of HCC after an incomplete response following TAE/TACE (NCT02323360). The primary endpoint is 1-year local control (LC): 18 events were needed to assess a 45% difference (HR: 0.18) in favor of SBRT. The secondary endpoints are 1-year Progression-Free Survival (PFS), Distant Recurrence-Free Survival (DRFS), Overall Survival (OS) and the incidence of acute and late complications. Results: At the time of the final analysis, 40 patients were enrolled, 19 (49%) in the TAE/TACE arm and 21 (51%) in the SBRT arm. The trial was prematurely closed due to slow accrual. The 1- and 2-year LC rates were 57% and 36%. The use of SBRT resulted in superior LC as compared to TAE/TACE rechallenge (median not reached versus 8 months, p = 0.0002). PFS was 29% and 16% at 1 and 2 years, respectively. OS was 86% and 62% at 1 year and 2 years, respectively. In the TAE arm, PFS was 13% and 6% at 1 and 2 years, respectively. In the SBRT arm, at 1 and 2 years, PFS was 37% and 21%, respectively. OS at 1 and 2 years was 75% and 64% in the SBRT arm and 95% and 57% in the TACE arm, respectively. No grade >3 toxicity was recorded. Conclusions: SBRT is an effective treatment option in patients affected by inoperable HCC experiencing an incomplete response following ≥1 cycle of TAE/TAC. Full article

Metastasis is a major cause of death in lung cancer patients. Therefore, a deeper understanding of the metastatic mechanisms is important for developing better management strategies for lung cancer patients. This study evaluated the patterns of extrathoracic metastases in lung cancer. We retrieved data for 25,103 lung cancer patients from an institutional database and then evaluated the impacts of clinicopathologic factors on metastasis patterns. We found that 36.5% of patients had extrathoracic metastasis. Younger patients had a significantly higher extrathoracic metastasis rate in most histologic subtypes. Metastases to the bone (58.3%), central nervous system (CNS) (44.3%), liver (26.6%) and adrenal gland (18.3%) accounted for 85.5% of all extrathoracic metastases. Patients with nonmucinous adenocarcinoma had significantly higher bone metastasis rate. Patients with small cell carcinoma and large cell neuroendocrine carcinoma (LCNEC) had significantly higher liver metastasis rates. Further, patients with LCNEC also had a significantly lower bone metastasis rate, and patients with squamous cell carcinoma had a significantly lower CNS metastasis rate. Patients with multiple cancers had similar patterns of metastasis compared to patients with only lung cancer. In conclusion, different histologic subtypes of lung cancer have different metastatic patterns. Our study might help clinicians decide on follow-up strategies. Full article

Recent advances in deep learning have enhanced medical imaging research. Breast cancer is the most prevalent cancer among women, and many applications have been developed to improve its early detection. The purpose of this review is to examine how various deep learning methods can be applied to breast cancer screening workflows. We summarize deep learning methods, data availability and different screening methods for breast cancer including mammography, thermography, ultrasound and magnetic resonance imaging. In this review, we will explore deep learning in diagnostic breast imaging and describe the literature review. As a conclusion, we discuss some of the limitations and opportunities of integrating artificial intelligence into breast cancer clinical practice. Full article

Research suggests that colorectal cancer (CRC) is associated with mental health disorders, primarily anxiety and depression. To synthesize this evidence, we conducted a systematic review and meta-analysis of studies evaluating the onset of anxiety and depression among patients with CRC. We searched EMBASE and Medline from inception to June 2022. We included original, peer-reviewed studies that: used an epidemiologic design; included patients with CRC and a comparator group of individuals without cancer; and evaluated anxiety and depression as outcomes. We used random effects models to obtain pooled measures of associations. Quality assessment was completed using the Newcastle-Ottawa scale. Of 7326 articles identified, 8 were eligible; of which 6 assessed anxiety and depression and 2 assessed depression only. Meta-analyses showed a non-significant association between CRC and anxiety (pooled HR 1.67; 95% CI 0.88 to 3.17) and a significant association between CRC and depression (pooled HR 1.78; 95% CI 1.23 to 2.57). Predictors of anxiety and depression among patients with CRC included clinical characteristics (e.g., comorbidities, cancer stage, cancer site), cancer treatment (e.g., radiotherapy, chemotherapy, colostomy), and sociodemographic characteristics (e.g., age, sex). The impacts of anxiety and depression in patients with CRC included increased mortality and decreased quality of life. Altogether, our systematic review and meta-analysis quantified the risks and impacts of CRC on anxiety and depression, particularly an increased risk of depression after CRC diagnosis. Findings provide support for oncologic care that encompasses mental health supports for patients with CRC. Full article

Breast tissue density (BTD) is known to increase the risk of breast cancer but is not routinely used in the risk assessment of the population-based High-Risk Ontario Breast Screening Program (HROBSP). This prospective, IRB-approved study assessed the feasibility and impact of incorporating breast tissue density (BTD) into the risk assessment of women referred to HROBSP who were not genetic mutation carriers. All consecutive women aged 40–69 years who met criteria for HROBSP assessment and referred to Genetics from 1 December 2020 to 31 July 2021 had their lifetime risk calculated with and without BTD using Tyrer-Cuzick model version 8 (IBISv8) to gauge overall impact. McNemar’s test was performed to compare eligibility with and without density. 140 women were referred, and 1 was excluded (BRCA gene mutation carrier and automatically eligible). Eight of 139 (5.8%) never had a mammogram, while 17/131 (13%) did not have BTD reported on their mammogram and required radiologist review. Of 131 patients, 22 (16.8%) were clinically impacted by incorporation of BTD: 9/131 (6.9%) became eligible for HROBSP, while 13/131 (9.9%) became ineligible (p = 0.394). It was feasible for the Genetics clinic to incorporate BTD for better risk stratification of eligible women. This did not significantly impact the number of eligible women while optimizing the use of high-risk supplemental MRI screening. Full article

In the 2016 WHO classification of tumors of the central nervous system, hemangiopericytomas (HPCs) and solitary fibrous tumors (SFTs) were integrated into a new entity (SFT/HPC). Metastases to bone, liver, lung, and abdominal cavity are of concern. Only 37 cases of patients with liver metastases due to intracranial SFTs/HPCs have been reported. Herein, we present our experience in the management of patients with liver metastases from intracranial SFTs/HCPs. All consecutive patients who were treated for liver metastases from intracranial SFTs/HPCs from January 2014 to December 2020 were enrolled. Overall, three patients were treated for liver metastasis from SFTs/HPCs with curative intent. Two patients with bilobar metastases at presentation required surgical resection, transarterial embolization, stereotactic radiofrequency ablation (SRFA) and systemic therapy. One patient with a singular right liver lobe metastasis was treated with SRFA alone. This patient shows no evidence of liver metastases 39 months following diagnosis. Of the two patients with bilobar disease, one died 89 months following diagnosis, while one is still alive 73 months following diagnosis. Long-term survival can be achieved using a multimodal treatment concept, including surgery, loco-regional and systemic therapies. Referral to a specialized tertiary cancer center and comprehensive long-term follow-up examinations are essential. Full article

Pancreatic cancer (PC) is a highly malignant and aggressive tumor. Despite medical advancement, the silent nature of PC results in only 20% of all cases considered resectable at the time of diagnosis. It is projected to become the second leading cause in 2030. Most pancreatic cancer cases are diagnosed in the advanced stages. Such cases are typically unresectable and are associated with a 5-year survival of less than 10%. Although there is no guideline consensus regarding recommendations for screening for pancreatic cancer, early detection has been associated with better outcomes. In addition to continued utilization of imaging and conventional tumor markers, clinicians should be aware of novel testing modalities that may be effective for early detection of pancreatic cancer in individuals with high-risk factors. The pathogenesis of PC is not well understood; however, various modifiable and non-modifiable factors have been implicated in pancreatic oncogenesis. PC detection in the earlier stages is associated with better outcomes; nevertheless, most oncological societies do not recommend universal screening as it may result in a high false-positive rate. Therefore, targeted screening for high-risk individuals represents a reasonable option. In this review, we aimed to summarize the pathogenesis, genetic risk factors, high-risk population, and screening modalities for PC. Full article

Background: A fixed dose of 200 mg of pembrolizumab every 3 weeks (Q3W) is the standard of care for patients with stage IV non-small cell lung cancer (NSCLC) and PDL1 ≥50%. In April 2020, based on pharmacokinetic modeling without formal comparative studies, the FDA approved 400 mg every 6 weeks (Q6W). Pharmacokinetic studies also suggested comparable target engagement with weight-based and flat dosing for the respective schedules. The objective of this study was to determine if overall survival (OS) differs based on the Q3W vs. Q6W dosing schedule of pembrolizumab. Methods: BC Cancer patients with stage IV NSCLC and PDL1 ≥50% treated with pembrolizumab were retrospectively reviewed. Patients were treated with weight-based dosing, per institution standard, of pembrolizumab 2 mg/kg Q3W or 4 mg/kg Q6W. Patient demographics, treatment and outcome were recorded. Patients were assigned to Q3W or Q6W according to the schedule that was used for the majority of treatment (greater than 50%). Results: 718 patients with NSCLC and PDL1 ≥50% received first-line pembrolizumab between 2017 and2021, Q3W/Q6W dosing 677/41 patients. Baseline characteristics with respect to age, sex, smoking status, histology and performance status (PS) were similar between groups. In the multivariate model, including age, sex, PS and dosing schedule, the hazard ratio for death (HR) for OS Q3W vs. Q6W was 0.759 (p = 0.230). A 2:1 case-matched analysis for OS was performed, controlling for sex, age ± 5 years, PS and duration on pembrolizumab ± 2 months for Q3W vs. Q6W (n = 113) with a HR 0.834 (p = 0.500). Conclusions: There was no OS difference demonstrated with pembrolizumab dosing Q3W compared to Q6W in a multivariate analysis that included age, sex and PS. A case-matched analysis that controlled for these variables and for duration of treatment confirmed these findings. This study supports the use of Q6W pembrolizumab dosing, allowing for less frequent interactions with the medical system. Full article

Background: We have recently reported a 35% drop in new lung cancer diagnoses and a 64% drop in lung cancer surgeries during the first year of the pandemic. Methods: The target population was divided into three cohorts: pre-COVID-19 (2019), first year of COVID-19 (2020), and second year of COVID-19 (2021). Results: The number of new lung cancer diagnoses during the second year of the pandemic increased by 75%, with more than 50% being in the advanced/metastatic stage. There was a significant increase in cases with multiple extrathoracic sites of metastases during the pandemic. During the first year of the pandemic, significantly more patients were treated with radiosurgery compared to the pre-COVID-19 year. During the second year, the number of radiosurgery and surgical cases returned to pre-COVID-19 levels. No significant changes were observed in systemic chemotherapy and targeted therapy. No statistical difference was identified in the mean wait time for diagnosis and treatment during the three years of observation. However, the wait time for surgery was prolonged compared to the pre-COVID-19 cohort. Conclusions: The significant drop in new diagnoses of lung cancer during the first year of the pandemic was followed by an almost two-fold increase in the second year, with the increased rate of metastatic disease with multiple extra-thoracic site metastases. Limited access to surgery resulted in the more frequent use of radiosurgery. Full article

Objective: To analyze the perioperative outcomes of neoadjuvant hormone therapy (NHT) before laparoscopic and robot-assisted surgery for localized high-risk prostate cancer in a Chinese cohort. Methods: The clinical data of 385 patients with localized high-risk prostate cancer who underwent radical prostatectomy (RP) in our hospital from January 2019 to June 2021 were analyzed retrospectively, including 168 patients with preoperative NHT and 217 patients with simple surgery. Clinical characteristics were compared in the above two groups, the laparoscopic RP (LRP) cohort (n = 234) and the robot-assisted laparoscopic radical prostatectomy (RALP) cohort (n = 151), respectively. Results: In the overall cohort, compared with the control group, the NHT group had a shorter operative time, less blood loss, a lower positive surgical margin rate, and a higher proportion of Gleason score (GS) downgrading after the operation (p < 0.05). However, there was no significant difference in hospitalization time, biochemical recurrence, urine leakage, urinary continence, or prostate-specific antigen (PSA) progression-free survival (p > 0.05). In the LRP cohort, it was found that the NHT group also had shorter operative time, less blood loss, lower positive surgical margin rate, a higher proportion of GS downgrading after the operation, and faster recovery of urinary control than the control group (p < 0.05). There was no marked difference in hospitalization time, biochemical recurrence, urinary leakage, or PSA progression-free survival. However, in the RALP cohort, the NHT group had a significant difference in the GS downgrading after the operation compared with the control group (p < 0.05). In the overall cohort, multiple analyses showed that initial PSA level, GS at biopsy, clinical T stage, lymph node invasion, use of NHT, and surgical methods were significantly associated with positive surgical margin (p < 0.05) while NHT did not account for biochemical recurrence (p > 0.05). Conclusions: NHT can lower the difficulty of surgery, reduce positive surgical margin rate, and help recovery in short-term urinary control in patients with high-risk prostate cancer after LRP. However, we do not have evidence on the benefit of NHT in high-risk PCa patients treated with RALP. For these patients, surgery can be performed as early as possible. Full article

Objective: Kruppel-associated box (KRAB) proteins reportedly play a dual role in neoplastic transformation. At present, little is known about the function of the proteins encoded by the human pogo transposable element derived with KRAB domain (POGK) gene. Herein, we evaluated the prognostic significance of POGK expression in patients with hepatocellular carcinoma (HCC). Methods: The data of HCC patients was downloaded from The Cancer Genome Atlas (TCGA) database. To determine the relationship between POGK and clinical features, logistic regression was applied. Cox regression and Kaplan-Meier analyses were used to evaluate the correlation between POGK and survival rates. Gene ontology (GO) analysis and Gene set enrichment analysis (GSEA) were conducted to identify the enriched pathways and functions associated with POGK. Results: A total of 374 HCC patients were identified in TCGA. POGK was significantly upregulated in HCC and correlated with tumor status (p = 0.036), race (p = 0.025), weight (p = 0.002), body mass index (p = 0.033), histologic grade (p < 0.001), and alpha-fetoprotein (p < 0.001). High POGK expression in HCC patients correlated with a poor outcome in terms of overall survival (p = 0.0018), progression-free survival (p = 0.0087), relapse-free survival (p = 0.045), and disease-specific survival (p = 0.014), according to Kaplan-Meier analysis. Receiver operating characteristic curve analysis showed that the area under the curve of POGK expression for HCC diagnosis was 0.891. GSEA showed that high POGK expression might activate mitotic prometaphase, kinesins, homologous DNA pairing and strand exchange, MET activates PTK2 signaling pathway, G1 to S cell cycle control, Aurora B pathway, ncRNAs involved in WNT signaling pathway, hepatitis C, and ncRNAs involved in the STAT3 signaling pathway. POGK expression correlated with the abundance of adaptive and innate immunocytes in HCC. Conclusion: High expression of POGK has high diagnostic and prognostic values in patients with HCC. Moreover, POGK expression is correlated with immune infiltration in HCC. Full article

Background: Hypoxia is recognized as a key feature of cancer growth and is involved in various cellular processes, including proliferation, angiogenesis, and immune surveillance. Besides hypoxia-inducible factor 1-alpha (HIF-1α), which is the main mediator of hypoxia effects and can also be activated under normoxic conditions, little is known about its counterpart, HIF-2. This study focused on investigating the clinical and molecular landscape of HIF-2-altered urothelial carcinoma (UC). Methods: Publicly available next-generation sequencing (NGS) data from muscle-invasive UC cell lines and patient tumor samples from the MSK/TCGA 2020 cohort (n = 476) were interrogated for the level of expression (mRNA, protein) and presence of mutations, copy number variations, structural variants in the EPAS1 gene encoding HIF-2, and findings among various clinical (stage, grade, progression-free and overall survival) and molecular (tumor mutational burden, enriched gene expression) parameters were compared between altered and unaltered tumors. Results: 19% (7/37) of UC cell lines and 7% (27/380) of patients with muscle-invasive UC display high EPAS1 mRNA and protein expression or/and EPAS1 alterations. EPAS1-altered tumors are associated with higher stage, grade, and lymph node metastasis as well as with shorter PFS (14 vs. 51 months, q = 0.01) and OS (15 vs. 55 months, q = 0.01). EPAS1 mRNA expression is directly correlated with that of its target-genes, including VEGF, FLT1, KDR, DLL4, CDH5, ANGPT1 (q < 0.001). While there is a slightly higher tumor mutational burden in EPAS1-altered tumors (9.9 vs. 4.9 mut/Mb), they are enriched in and associated with genes promoting immune evasion, including ARID5B, SPINT1, AAK1, CLIC3, SORT1, SASH1, and FGFR3, respectively (q < 0.001). Conclusions: HIF-2-altered UC has an aggressive clinical and a distinct genomic and immunogenomic profile enriched in angiogenesis- and immune evasion-promoting genes. Full article

Background: The introduction of novel hormonal agents (NHAs) such as abiraterone acetate (ABI) and enzalutamide (ENZ) for metastatic castration-resistant prostate cancer (mCRPC) was an important milestone given their survival benefits, tolerability, and ease of administration relative to taxane chemotherapies. This descriptive study sought to describe the utilization trends of ABI and ENZ in patients with mCRPC in the early years after their approval in the province of Quebec in Canada. Methods: A retrospective population-based cohort was extracted from Quebec public healthcare administrative databases. The cohort included first-time users of NHAs (ABI or ENZ) from 2011 to 2016. The primary analyses aimed to describe the overall temporal trends (2011–2016) of NHA initiators by chemotherapy status (chemotherapy-naïve versus post-chemotherapy), and prescribing specialty (medical oncology versus urology versus others). Results: The cohort comprised 2183 patients, with 1562 (72%) in the chemotherapy-naïve group and 621 (28%) in the post-chemotherapy group. While the majority of patients were post-chemotherapy NHA initiators in 2012, this proportion decreased over time and accounted for only 13% of NHA initiators by the end of 2016. Medical oncologists were the most frequent prescribers of NHAs (upwards of 60%) throughout 2012 but fell to 45% by the end of 2016. Conversely, the proportion of prescriptions by urologists increased from 22% in 2012 to 42% in 2016. Conclusion: Over time, there was an increasing proportion of (1) patients who initiated NHAs without prior chemotherapy treatment, (2) NHA prescribing by urologists, and (3) ENZ users. Taken together, this implies that the introduction of NHAs has altered the management of mCRPC and urologists quickly adopted NHAs into their practice. Full article

Outcome disparities between adults <50 with colorectal cancer (CRC) and older adults may be explained by clinical delays. This study synthesized the literature comparing delays and outcomes between younger and older adults with CRC. Databases were searched until December 2021. We included studies published after 1990 reporting delay in adults <50 that made comparisons to older adults. Comparisons were described narratively and stage between age groups was meta-analyzed. 39 studies were included representing 185,710 younger CRC patients and 1,422,062 older patients. Sixteen delay intervals were compared. Fourteen studies (36%) found significantly longer delays among younger adults, and nine (23%) found shorter delays among younger patients. Twelve studies compared time from symptom onset to diagnosis (N younger = 1538). Five showed significantly longer delays for younger adults. Adults <50 years also had higher odds of advanced stage (16 studies, pooled OR for Stage III/IV 1.76, 95% CI 1.52–2.03). Ten studies compared time from diagnosis to treatment (N younger = 171,726) with 4 showing significantly shorter delays for younger adults. All studies showing longer delays for younger adults examined pre-diagnostic intervals. Three studies compared the impact of delay on younger versus older adult. One showed longer delays were associated with advanced stage and worse survival in younger but not older adults. Longer delays among younger adults with CRC occur in pre-diagnostic intervals. Full article

Robotic surgery is increasingly gaining importance. While initial results suggest an advantage of the robotic over the minimally invasive approach in patients with gastric cancer, definitive proof of its superiority has yet to be provided. There are numerous approaches to recreate a gastric reservoir after a total gastrectomy. However, a major disadvantage of most conventional reconstructions are long term effects such as dumping syndrome, afferent loop syndrome and poor nutrition intake with severe impact on the patient quality of life. The jejunal pouch reconstruction is a beneficial reconstruction, which provides a larger reservoir capacity after gastrectomy and prevents anastomotic stenosis and dumping syndrome. The completely intercorporeal approach with a Pfannenstiel incision instead of an unfavorable midline incision can potentially decrease delayed complications such as incision hernias. With the increased deployment of robotic surgery, a complete intercorporeal reconstruction is now possible without major increase in operating time or further technical weak points. We provide for the first time a detailed technical explanation of the completely intercorporeal robotic jejunal pouch reconstruction after gastrectomy. Full article