Current Oncology

The transverse myocutaneous gracilis (TMG) and the profunda artery perforator (PAP) flap are both safe choices for autologous breast reconstruction originating from the same donor region in the upper thigh. We aimed to compare the post-operative outcome regarding donor-site morbidity and quality of life. We included 18 patients who had undergone autologous breast reconstruction with a PAP flap (n = 27 flaps). Prospective evaluation of donor-site morbidity was performed by applying the same questionnaire that had already been established in a previous study evaluating TMG flap (n = 25 flaps) outcome, and results were compared. Comparison of the two patient groups showed equivalent results concerning patient-reported visibility of the donor-site scar and thigh symmetry. Still, the TMG group was significantly more satisfied with the scar (p = 0.015) and its position (p = 0.001). No difference was found regarding the ability to sit for prolonged periods. Donor-site wound complications were seen more frequently in the PAP group (29.6%) than in the TMG group (4.0%). Both groups expressed rather high satisfaction with their quality of life. Both flaps show minimal functional donor-site morbidity and high patient satisfaction. To minimize wound healing problems in PAP patients, thorough planning of the skin paddle is necessary. Full article

Columnar cell lesions (CCLs) of the breast comprise a spectrum of morphologic alterations of the terminal duct lobular unit involving variably dilated and enlarged acini lined by columnar epithelial cells. The World Health Organization currently classifies CCLs without atypia as columnar cell change (CCC) and columnar cell hyperplasia (CCH), whereas flat epithelial atypia (FEA) is a unifying term encompassing both CCC and CCH with cytologic atypia. CCLs have been increasingly recognized in stereotactic core needle biopsies (CNBs) performed for the assessment of calcifications. CCLs are believed to represent the earliest non-obligate precursor of low-grade invasive breast carcinomas as they share molecular alterations and often coexist with entities in the low-grade breast neoplasia pathway. Despite this association, however, the risk of progression of CCLs to invasive breast carcinoma appears low and may not exceed that of concurrent proliferative lesions. As the reported upgrade rates of pure CCL/FEA when identified as the most advanced high-risk lesion on CNB vary widely, the management of FEA diagnosed on CNB remains controversial. This review will include a historical overview of CCLs and will examine histologic diagnostic criteria, molecular alterations, prognosis and issues related to upgrade rates and clinical management. Full article

Background: The present study was conducted to define the lymphedema rate at our institution in patients undergoing axillary (ALND) or inguinal (ILND) lymph node dissection (LND) for melanoma. It aimed to examine risk factors predisposing patients to a higher rate of lymphedema, highlighting which patients could be targeted for immediate lymphatic reconstruction (ILR). Methods: A retrospective chart review was conducted between October 2015 and July 2020 to identify patients who had undergone ALND or ILND for melanoma. The main outcome measures were rates of transient and permanent lymphedema. Univariate and multivariate analyses were performed to assess the relationship between lymphedema rate and factors related to patient characteristics, surgical procedure, pathology findings, and adjuvant treatment. Results: Between October 2015 and July 2020, 66 patients underwent LND for melanoma: 34 patients underwent ALND and 32 patients underwent ILND. At a median follow-up of 29 months, 85.3% (n = 29) of patients having had an ALND did not experience lymphedema, versus 50.0% (n = 16) of ILND (p = 0.0019). The rates of permanent lymphedema for patients having undergone ALND and ILND were 11.8% (n = 4) and 37.5% (n = 12) respectively (p = 0.016, NS). The rate of transient lymphedema was 2.9% (n = 1) for ALND and 12.5% (n = 4) for ILND (p = 0.13, NS). On univariate analysis, the location of LND and wound infection were found to be significant factors for lymphedema. On multivariate analysis, only the location of LND remained a significant predictor, with the inguinal location predisposing to lymphedema. Conclusion: This study highlights the high rate of lymphedema following ILND for melanoma and is a potential target for future patients to be considered for ILR. Full article

Quality medical practice is based on science and evidence. For over a half-century, the efficacy of breast cancer screening has been challenged, particularly for women aged 40–49. As each false claim has been raised, it has been addressed and refuted based on science and evidence. Nevertheless, misinformation continues to be promoted, resulting in confusion for women and their physicians. Early detection has been proven to save lives for women aged 40–74 in randomized controlled trials of mammography screening. Observational studies, failure analyses, and incidence of death studies have provided evidence that there is a major benefit when screening is introduced to the general population. In large part due to screening, there has been an over 40% decline in deaths from breast cancer since 1990. Nevertheless, misinformation about screening continues to be promoted, adding to the confusion. Despite claims to the contrary, a careful reading of the guidelines issued by major groups such as the U.S. Preventive Services Task Force and the American College of Physicians shows that they all agree that most lives are saved by screening starting at the age of 40. There is no scientific support for using the age of 50 as a threshold for screening. All women should be provided with the facts and not false information about breast cancer screening so that they can make “informed decisions” for themselves about whether to participate. Full article

The relationship between Canadian mammography screening practices for women 40–49 and breast cancer (BC) stage at diagnosis in women 40–49 and 50–59 years was assessed using data from the Canadian Cancer Registry, provincial/territorial screening practices, and screening information from the Canadian Community Health Survey. For the 2010 to 2017 period, women aged 40–49 were diagnosed with lesser relative proportions of stage I BC (35.7 vs. 45.3%; p < 0.001), but greater proportions of stage II (42.6 vs. 36.7%, p < 0.001) and III (17.3 vs. 13.1%, p < 0.001) compared to women 50–59. Stage IV was lower among women 40–49 than 50–59 (4.4% vs. 4.8%, p = 0.005). Jurisdictions with organised screening programs for women 40–49 with annual recall (screeners) were compared with those without (comparators). Women aged 40–49 in comparator jurisdictions had higher proportions of stages II (43.7% vs. 40.7%, p < 0.001), III (18.3% vs. 15.6%, p < 0.001) and IV (4.6% vs. 3.9%, p = 0.001) compared to their peers in screener jurisdictions. Based on screening practices for women aged 40–49, women aged 50–59 had higher proportions of stages II (37.2% vs. 36.0%, p = 0.003) and III (13.6% vs. 12.3%, p < 0.001) in the comparator versus screener groups. The results of this study can be used to reassess the optimum lower age for BC screening in Canada. Full article

The Canadian Real-world Evidence for Value in Cancer Drugs (CanREValue) Collaboration established the Engagement Working Group (WG) to ensure that all key stakeholders had an opportunity to provide input into the development and implementation of the CanREValue Real-World Evidence (RWE) Framework. Two consultations were held in 2021 to solicit patient perspectives on key policy and data access issues identified in the interim policy and data WG reports. Over 30 individuals, representing patients, caregivers, advocacy leaders, and individuals engaged in patient research were invited to participate. The consultations provided important feedback and valuable lessons in patient engagement. Patient leaders actively shaped the process and content of the consultation. Breakout groups facilitated by patient advocacy leaders gave the opportunity for open and thoughtful contributions from all participants. Important recommendations were made: the RWE framework should not impede access to new drugs; it should be used to support conditional approvals; patient relevant endpoints should be captured in provincial datasets; access to data to conduct RWE should be improved; and privacy issues must be considered. The manuscript documents the CanREValue experience of engaging patients in a consultative process and the useful contributions that can be achieved when the processes to engage are guided by patients themselves. Full article

In Switzerland, physicians do not have national guidelines for metastatic colorectal cancer (mCRC) patient care and utilize international versions for management recommendations. Moreover, information about adherence to these guidelines and real-world practice patterns in Switzerland or other countries is lacking. The Screening and COnsensus based on Practices and Evidence (SCOPE) program were designed by an international expert panel of gastrointestinal oncologists to gather real-world insights in the current clinical setting to manage patients with mCRC who have received prior treatment. We sought to understand general practice patterns, the influence of molecular diagnostics (e.g., testing for KRAS, NRAS, BRAF, and MSI), tumor sidedness, and patient-centric factors on treatment selection utilizing in-person surveys and three hypothetical patient case scenarios. Here, we describe and evaluate the Swiss data from the SCOPE program within the context of an international viewpoint and discuss the findings of our analysis. In general, we find that the real-world clinical decisions of Swiss physicians (SWI) closely follow international (INT) recommendations and guidelines, largely paralleling their regional and international counterparts in using the two approved treatments in the third- and fourth-line settings, namely trifluridine-tipiracil and regorafenib. Finally, our data suggest a tendency toward the use of trifluridine-tipiracil (SWI: 79%; INT: 66%) over regorafenib (SWI: 18%; INT: 18%) as the preferred third-line treatment choice in mCRC patients regardless of KRAS status. Full article

The main role of the host immune system is to identify and eliminate cancer cells, which is a complex process, but it is not a fail-safe mechanism. Many sarcoma patients succumb to this disease despite treatments rendered. The aim of this pilot study was to compare the levels of CD4⁺ T-cells, T-regulatory (Treg) cells, and cytokines such as tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-17A (IL-17A), and transforming growth factor-beta-1 (TGF-β1) in peripheral blood leukocytes of sarcoma patients and healthy controls. For gene expression studies, total ribonucleic acid (RNA) was extracted from peripheral blood leukocytes and genes that were differentially regulated in peripheral blood leukocytes of sarcoma patients compared with healthy controls were determined using a commercial T-helper cell differentiation quantitative polymerase chain reaction (qPCR) array. Flow cytometer analysis was performed on blood samples from 26 sarcoma patients and 10 healthy controls to identify the levels of CD4⁺ T-cells and T-reg cells. The level of cytokines in plasma and culture supernatant were quantified using commercial enzyme-linked immunosorbent assay (ELISA) kits. A marked reduction in the percentage of CD4⁺ T-cells (p = 0.037) and levels of TNF-α (p = 0.004) and IFN-γ (0.010) was observed in sarcoma patients. Gene expression analysis showed five genes (homeobox A10 (HOXA10), GATA binding protein 3 (GATA3), prostaglandin D2 receptor 2 (PTGDR2), thymocyte selection associated high mobility group box (TOX), and C-C motif chemokine receptor 3 (CCR3)) were dysregulated (p < 0.05) in sarcoma patients. This study suggests that T-helper-1 immune responses are reduced in sarcoma patients. Full article

Pediatric oncologists have the privilege of caring for children and families facing serious, often life-threatening, illnesses. Providing this care is emotionally demanding and associated with significant risks of stress and burnout for oncologists. Traditional approaches to physician burnout and wellbeing have not emphasized the potential roles of education and training in mitigating this stress. In this commentary, we discuss the contribution that education, particularly in the areas of palliative and psychosocial oncology, can make in preparing oncologists for the work that they do. We argue that by adequately providing oncologists with the skills they need for their work, we can reduce their risk of burning out. We also discuss the importance of paying attention to hidden and formal curricula to ensure that messages provided in formal education programs are supported by informal training experiences. Full article

Background: Since cancer pain requires complex modalities of care, the proper strategy for addressing its telemedicine-based management should be better defined. This study aimed to trace a pathway for a progressive implementation of the telemedicine process for the treatment of pain in the setting of cancer patients. Methods: The features of the model were investigated to dissect the dropout from the telemedicine pathway. A cross-sectional patient satisfaction study was conducted. The degree of satisfaction was evaluated through a developed 22-item questionnaire (Likert scale 0–7). Results: A total of 375 video consultations for 164 patients (mean age 62.9 years) were performed through remote consultations for cancer pain management between March 2021 and February 2022. After the exclusion of 72 patients, 92 (56.1%) were included in the analysis. The dropout ratio was 8.7%. The number of visits and pharmacological therapies for neuropathic pain correlated with the risk for readmission (p < 0.05). Overall, the satisfaction was very high (mean > 5.5 for all items). Conclusion: Feedback from patients reflected high satisfaction rates with the care provided. A methodological approach based on the degree of satisfaction combined with the analysis of the pathways can help to implement the quality of a service provided through telemedicine. While not without limitations, our hybrid protocol can be useful for addressing cancer pain through a patient-centered approach. Full article

Somatostatin receptor (SSTR)-targeted peptide receptor radionuclide therapy (PRRT) represents a promising approach for treatment-refractory meningiomas progressing after surgery and radiotherapy. The aim of this study was to provide outcomes of patients harboring refractory meningiomas treated by 177Lu-DOTATATE and an overall analysis of progression-free survival at 6 months (PFS-6) of the same relevant studies in the literature. Eight patients with recurrent and progressive WHO grade II meningiomas were treated after multimodal pretreatment with 177Lu-DOTATATE between 2019 and 2022. Primary and secondarily endpoints were progression-free survival at 6-months (PFS-6) and toxicity, respectively. PFS-6 analysis of our case series was compared with other similar relevant studies that included 86 patients treated with either 177Lu-DOTATATE or 90Y-DOTATOC. Our retrospective study showed a PFS-6 of 85.7% for WHO grade II progressive refractory meningiomas. Treatment was clinically and biologically well tolerated. The overall analysis of the previous relevant studies showed a PFS-6 of 89.7% for WHO grade I meningiomas (n = 29); 57.1% for WHO grade II (n = 21); and 0 % for WHO grade III (n = 12). For all grades (n = 86), including unknown grades, PFS-6 was 58.1%. SSTR-targeted PRRT allowed us to achieve prolonged PFS-6 in patients with WHO grade I and II progressive refractory meningiomas, except the most aggressive WHO grade II tumors. Large scale randomized trials are warranted for the better integration of PRRT in the treatment of refractory meningioma into clinical practice guidelines. Full article

Deregulation of the DNA mismatch repair (MMR) mechanism has been linked to poor prognosis of upper aerodigestive tract cancers. Our recent in vitro data have provided evidence of crosstalk between deregulated miRNAs and MMR genes, caused by tobacco smoke (TS) N-Nitrosamines, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), in hypopharyngeal cells. Here, we explored whether chronic exposure to TS components can affect MMR mechanism and miRNA profiles in hypopharyngeal mucosa. Using a mouse model (C57Bl/6J wild type) of in vivo 14-week exposure to NNK (0.2 mmol/L) and N-Nitrosodiethylamine (NDEA; 0.004 mmol/L), with or without nicotine (0.02 μmol/L), we provide direct evidence that TS components can promote dysplasia, significant downregulation of Msh2 and Mlh1 genes and deregulation of miR-21, miR-155, miR-34a, and miR-451a. By analyzing eight human specimens from tobacco smokers and eight controls, we provide clinical evidence of a significant reduction in hMSH2 and hMLH1 mRNAs in hypopharyngeal squamous cell carcinoma (HSCC). In summary, deregulation of the MMR mechanism and miRNAs is caused by chronic exposure to TS-related N-Nitrosamines, with or without nicotine, in the early stages of upper aerodigestive tract carcinogenesis, and can also be detected in human HSCC. Thus, we encourage future studies to further elucidate a possible in vivo dose-dependent effect of individual or combined N-Nitrosamines, NNK and/or NDEA, and nicotine, on the MMR mechanism and their clinical testing to elaborate prognosis and risk assessment. Full article

The development of new screening methods and diagnostic tests for traits, common diseases, and cancer is linked to the advent of precision genomic medicine, in which health care is individually adjusted based on a person’s lifestyle, environmental influences, and genetic variants. Based on genome-wide association study (GWAS) analysis, rapid and continuing progress in the discovery of relevant single nucleotide polymorphisms (SNPs) for traits or complex diseases has increased interest in the potential application of genetic risk models for routine health practice. The polygenic risk score (PRS) estimates an individual’s genetic risk of a trait or disease, calculated by employing a weighted sum of allele counts combined with non-genetic variables. However, 98.38% of PRS records held in public databases relate to the European population. Therefore, PRSs for multiethnic populations are urgently needed. We performed a systematic review to discuss the role of polygenic risk scores in advancing precision medicine for different cancer types in multiethnic non-European populations. Full article

Aim: To compare digital breast tomosynthesis (DBT) and ultrasound in women recalled for assessment after a positive screening mammogram and assess the potential for each of these tools to reduce unnecessary biopsies. Methods: This data linkage study included 538 women recalled for assessment from January 2017 to December 2019. The association between the recalled mammographic abnormalities and breast density was analysed using the chi-square independence test. Relative risks and the number of recalled cases requiring DBT and ultrasound assessment to prevent one unnecessary biopsy were compared using the McNemar test. Results: Breast density significantly influenced recall decisions (p < 0.001). Ultrasound showed greater potential to decrease unnecessary biopsies than DBT: in entirely fatty (21% vs. 5%; p = 0.04); scattered fibroglandular (23% vs. 10%; p = 0.003); heterogeneously dense (34% vs. 7%; p < 0.001) and extremely dense (39% vs. 9%; p < 0.001) breasts. The number of benign cases needing assessment to prevent one unnecessary biopsy was significantly lower with ultrasound than DBT in heterogeneously dense (1.8 vs. 7; p < 0.001) and extremely dense (1.9 vs. 5.1; p = 0.03) breasts. Conclusion: Women with dense breasts are more likely to be recalled for assessment and have a false-positive biopsy. Women with dense breasts benefit more from ultrasound assessment than from DBT. Full article

Hepatocellular carcinoma (HCC) has high mortality. The option of systemic therapy has increased significantly over the past five years. Sorafenib was the first multikinase inhibitor, introduced in 2007, as a treatment option for HCC, and it was the only effective systemic treatment for more than ten years. It was not until 2017 that several breakthroughs were made in the development of systemic strategies. Lenvatinib, another multikinase inhibitor, stood out successfully after sorafenib, and has been applied to clinical use in the first-line setting. Other multikinase inhibitors such as regorafenib, ramucirumab and cabozantinib, were approved in quick succession as second-line therapies. Concurrently, immune checkpoint inhibitors (ICIs) have readily become established treatments for many solid tumors, including HCC. The most studied ICIs to date, target programmed cell death-1 (PD-1), its ligand PD-L1, and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). These ICIs have demonstrated efficacy in treating advanced HCC. More recently, combination of bevacizumab and atezolizumab (ICI targeting PD-L1) was approved as the gold-standard first-line therapy. Combination of ICIs with nivolumab and ipilimumab was also approved in the second-line setting for those who failed sorafenib. At the moment, numerous clinical trials in advanced HCC are underway, which will bring continuous change to the management, and increase the survival, for patients with advanced HCC. Our review article: (1) summarizes United States Food and Drug Administration (US FDA) approved systemic therapies in advanced HCC, (2) reports the evidence of currently approved treatments, (3) discusses potential drugs/drug combinations being currently tested in phase III clinical trials, and (4) proposes possible future directions in drug development for advanced HCC. Full article

Background: Renal cell carcinoma with sarcomatoid dedifferentiation represents a rare histological entity characterized by aggressive behavior, limited efficacy of tyrosine kinase inhibitors or mTOR inhibitors, and poor outcome. The immune checkpoint inhibitor therapy regimen combining ipilimumab with nivolumab represents a new standard of care for this patient population due to a hitherto unprecedented response rate and overall survival. On the other hand, the role of cytoreductive nephrectomy in metastatic renal cell carcinoma, in particular, with sarcomatoid histology, remains controversial. Patient and Methods: In the present case series, we report six patients with locally advanced or synchronous metastatic sarcomatoid renal cell carcinoma and intermediate or poor International Metastatic RCC Database Consortium (IMDC) risk score, five of whom were successfully subjected to cytoreductive nephrectomy. Results: All six patients received the combination regimen of ipilimumab with nivolumab. Five of these patients underwent upfront cytoreductive nephrectomy followed by systemic treatment without any significant delay, with a durable treatment outcome. Notably, two patients with poor prognostic features achieved a long-term major partial response to therapy. We also performed a review of the literature on optimal treatment strategies for patients with sarcomatoid renal cell carcinoma. Conclusion: Herein, we highlight the feasibility of performing cytoreductive nephrectomy in patients with intermediate/poor prognosis metastatic renal cell carcinoma with sarcomatoid dedifferentiation followed by immunotherapy with ipilimumab and nivolumab. To enhance the chances of immunotherapy success, cytoreductive nephrectomy should also be considered for patients presenting with a disease with adverse prognostic parameters. Full article

We aimed to identify prognostic predictive factors of patients with penile squamous cell carcinoma (PSCC). This retrospective study reviewed the clinical and pathological data of patients with PSCC at 10 institutions in Japan between January 2008 and December 2019. The primary endpoint was cancer-specific survival (CSS). We also identified useful predictive factors for CSS in patients with PSCC. In total, 64 patients with PSCC were enrolled. At the end of the follow-up period, 15 patients (23.4%) died owing to PSCC and six (9.4%) died owing to other causes. The 2- and 3-year CSS rates were 78.9% and 76.6%, respectively. Using the Kaplan–Meier method, the Eastern Cooperative Oncology Group performance status 0, serum albumin levels ≥4.2 g/dL, hemoglobin levels ≥13.2 g/dL, C-reactive protein levels <0.21 mg/dL, clinical T stage ≤2, clinically negative lymph node (LN) status, and tumor size <30 mm were associated with a significantly better CSS. In the multivariate analysis, the clinically positive LN status was a significant predictive factor for CSS in patients with PSCC. Further prospective large-scale and long-term studies are required to validate our findings. Full article

Reliable non-invasive biomarkers for the surveillance of patients at risk of hepatocellular carcinoma (HCC) development represent an unmet medical need. Recently, the liver-cancer-specific isoform of serine protease inhibitor Kazal (LC-SPIK) has been proposed as a valuable biomarker for the detection of HCC in patients with chronic liver disease of viral etiology. In the present study, we assessed the diagnostic accuracy of LC-SPIK, alone or in combination with standard serologic biomarkers (i.e., alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II, PIVKA-II), for the detection of HCC among patients with dysmetabolic liver disease. A total of 120 patients with non-alcoholic fatty liver disease (NAFLD), including 62 patients with a diagnosis of HCC and 58 with cirrhosis but without tumor, were retrospectively analyzed. The serum levels of LC-SPIK were measured by enzyme-linked immunosorbent assay (ImCare Biotech, Doylestown, PA). The serum LC-SPIK values were significantly different between patients with HCC (24.3, 17.6–39.8 ng/mL) and those with cirrhosis but without tumor (11.7, 8.7–18.2 ng/mL) (p < 0.001). By receiver operating characteristic curve analysis, we observed an area under the curve (AUC) of 0.841 for the detection of HCC; the combination with PIVKA-II further increased the accuracy to AUC = 0.926 (cross-validation). The promising results observed in the present pilot study foster additional research to investigate the usefulness of LC-SPIK for the stratification of the risk of HCC development in patients with NAFLD and advanced liver disease. Full article

Objectives: The molecular landscape of non-muscle-invasive (NMIBC) and muscle-invasive (MIBC) bladder cancer based on molecular characteristics is essential but poorly understood. In this pilot study we aimed to identify a multi-omics signature that can distinguish MIBC from NMIBC. Such a signature can assist in finding potential mechanistic biomarkers and druggable targets. Methods: Patients diagnosed with NMIBC (n = 15) and MIBC (n = 11) were recruited at a tertiary-care hospital in Nanjing from 1 April 2021, and 31 July 2021. Blood, urine and stool samples per participant were collected, in which the serum metabolome, urine metabolome, gut microbiome, and serum extracellular vesicles (EV) proteome were quantified. The differences of the global profiles and individual omics measure between NMIBC vs. MIBC were assessed by permutational multivariate analysis and the Mann–Whitney test, respectively. Logistic regression analysis was used to assess the association of each identified analyte with NMIBC vs. MIBC, and the Spearman correlation was used to investigate the correlations between identified analytes, where both were adjusted for age, sex and smoking status. Results: Among 3168 multi-omics measures that passed the quality control, 159 were identified to be differentiated in NMIBC vs. MIBC. Of these, 46 analytes were associated with bladder cancer progression. In addition, the global profiles showed significantly different urine metabolome (p = 0.029), gut microbiome (p = 0.036), and serum EV (extracellular vesicles) proteome (p = 0.039) but not serum metabolome (p = 0.059). We also observed 17 (35%) analytes that had been developed as drug targets. Multiple interactions were obtained between the identified analytes, whereas for the majority (61%), the number of interactions was at 11–20. Moreover, unconjugated bilirubin (p = 0.009) and white blood cell count (p = 0.006) were also shown to be different in NMIBC and MIBC, and associated with 11 identified omics analytes. Conclusions: The pilot study has shown promising to monitor the progression of bladder cancer by integrating multi-omics data and deserves further investigations. Full article