Current Oncology

The current paper is a retrospective cohort study conducted on sixty-seven patients who underwent two-stage breast reconstruction over a 5-year period (2015–2020). Forty-one (61.2%) patients received radiotherapy (RT group), and twenty-six (38.8%) did not (non-RT group). Data regarding patients, oncological therapies, type of reconstruction, time of hospitalization, complications, and costs were collected. The statistical analysis was performed using IBM SPSS Statistics 25. General complications were noted for 18 patients (43.9%) in the RT group and for 7 patients (26.9%) in the non-RT group. Major complications were observed only in the first group (five patients–12.2%). The mean time of hospitalization in the RT group was 14.83 days for patients with complications versus 9.83 days for those without complications and 15.5 days versus 8.63 days, respectively, in the non-RT group. The mean cost for patients without complications was 235.64 euros, whereas the cost for patients with complications was 330.24 euros (p = 0.001). Radiation therapy can affect the overall outcome by increasing the risk of complications and increasing costs; however, our paper shows that the association of alloplastic reconstruction in patients with radiotherapy can be performed safely and with low costs in carefully selected patients. Full article

Background: The International Prognostic Index (IPI) is applied to predict the outcome of chronic lymphocytic leukemia (CLL) with five prognostic factors, including genetic analysis. We investigated whether multiparameter flow cytometry (MPFC) data of CLL samples could predict the outcome by methods of explainable artificial intelligence (XAI). Further, XAI should explain the results based on distinctive cell populations in MPFC dot plots. Methods: We analyzed MPFC data from the peripheral blood of 157 patients with CLL. The ALPODS XAI algorithm was used to identify cell populations that were predictive of inferior outcomes (death, failure of first-line treatment). The diagnostic ability of each XAI population was evaluated with receiver operating characteristic (ROC) curves. Results: ALPODS defined 17 populations with higher ability than the CLL-IPI to classify clinical outcomes (ROC: area under curve (AUC) 0.95 vs. 0.78). The best single classifier was an XAI population consisting of CD4+ T cells (AUC 0.78; 95% CI 0.70–0.86; p < 0.0001). Patients with low CD4+ T cells had an inferior outcome. The addition of the CD4+ T-cell population enhanced the predictive ability of the CLL-IPI (AUC 0.83; 95% CI 0.77–0.90; p < 0.0001). Conclusions: The ALPODS XAI algorithm detected highly predictive cell populations in CLL that may be able to refine conventional prognostic scores such as IPI. Full article

Outcomes for patients with high-grade glioma remain poor. Temozolomide (TMZ) is the only drug approved for first-line treatment of glioblastoma multiforme, the most aggressive form of glioma. Chronotherapy highlights the potential benefit of timed TMZ administration. This is based on pre-clinical studies of enhanced TMZ-induced glioma cytotoxicity dependent on circadian, oscillating expression of key genes involved in apoptosis, DNA damage repair, and cell-cycle mediated cell death. The current systematic review’s primary aim was to evaluate the efficacy and toxicity of TMZ chronotherapy. A systemic review of literature following PRISMA guidelines looking at clinical outcomes on TMZ chronotherapy on gliomas was performed. The search in the English language included three databases (PubMed, EMBASE, and Cochrane) and five conferences from 1946 to April 2022. Two independent reviewers undertook screening, data extraction, and risk-of-bias assessment. A descriptive analysis was conducted due to limited data. Of the 269 articles screened, two unique studies were eligible and underwent abstraction for survival and toxicity findings. Both studies—one a retrospective cohort study (n = 166) and the other a prospective randomized feasibility study (n = 35)—were conducted by the same academic group and suggested a trend for improved overall survival, but possibly increased toxicity when TMZ was administered in the morning (vs. evening). There was limited evidence suggesting possible therapeutic value from administering TMZ in the morning, which may be consistent with the pre-clinical observations of the importance of the timing of TMZ administration in vitro. Larger, pragmatic, prospective randomized controlled trials are needed to ascertain the value of TMZ chronotherapy to provide optimized and equitable care for this population. Full article

Background: To optimize results reporting after penile cancer (PC) surgery, we proposed a Tetrafecta and assessed its ability to predict overall survival (OS) probabilities. Methods: A purpose-built multicenter, multi-national database was queried for stage I–IIIB PC, requiring inguinal lymphadenectomy (ILND), from 2015 onwards. Kaplan–Meier (KM) method assessed differences in OS between patients achieving Tetrafecta or not. Univariable and multivariable regression analyses identified its predictors. Results: A total of 154 patients were included in the analysis. The 45 patients (29%) that achieved the Tetrafecta were younger (59 vs. 62 years; p = 0.01) and presented with fewer comorbidities (ASA score ≥ 3: 0% vs. 24%; p < 0.001). Although indicated, ILND was omitted in 8 cases (5%), while in 16, a modified template was properly used. Although median LNs yield was 17 (IQR: 11–27), 35% of the patients had <7 nodes retrieved from the groin. At Kaplan–Maier analysis, the Tetrafecta cohort displayed significantly higher OS probabilities (Log Rank = 0.01). Uni- and multivariable logistic regression analyses identified age as the only independent predictor of Tetrafecta achievement (OR: 0.97; 95%CI: 0.94–0.99; p = 0.04). Conclusions: Our Tetrafecta is the first combined outcome to comprehensively report results after PC surgery. It is widely applicable, based on standardized and reproducible variables and it predicts all-cause mortality. Full article

The decision to treat advanced gastroesophageal cancers (GECs) with targeted therapy and immunotherapy is based on key biomarker expression (human epidermal growth factor receptor 2 (HER2), programmed cell death-ligand 1 (PD-L1), microsatellite instability (MSI), and/or mismatch repair (MMR)). Real-world data on testing, results, and treatment patterns are limited. This retrospective observational study used a nationwide electronic health record-derived de-identified database of patients from the United States. The analysis included adult patients with advanced GECs who initiated systemic treatment between 2017 and 2020. Biomarker testing patterns, timing, assays, tissue collection site, results, and treatment sequences were assessed. Of 1142 eligible patients, adenocarcinoma was the most prevalent histology (83% of patients). Overall, 571 (50%) patients were tested for PD-L1, 582 (51%) were tested for MMR/MSI, and 857 (75%) were tested for HER2. Between 2017 and 2020, the PD-L1 testing rate increased from 39% to 58%, and the MMR/MSI testing rate increased from 41% to 58%; the median time from initial diagnosis to first test decreased for both biomarkers. Programmed cell death receptor-1 inhibitor use was observed among patients with positive PD-L1 or MMR-deficient/MSI-High results. These results supplement data reported in key clinical trials and may inform decision-making as treatment options for advanced GECs evolve. Full article

Background: The prognostic importance of osteopenia in patients with intrahepatic cholangiocarcinoma (ICC) undergoing hepatectomy is unclear. The aim of this study was to evaluate the impact of osteopenia on survival in patients with ICC. Methods: A total of 71 patients who underwent hepatectomy at Jichi Medical University between July 2008 and June 2022 were included in this study. Non-contrast computed tomography scan images at the eleventh thoracic vertebra were used to assess bone mineral density. The cutoff value was calculated using a threshold value of 160 Hounsfield units. Overall survival curves were made using the Kaplan–Meier method and the log-rank test was used to evaluate survival. The hazard ratio (HR) and 95% confidence interval (CI) for overall survival were calculated using Cox’s proportional hazard model. Results: In multivariable analysis, osteopenia (HR 3.66, 95%CI 1.16–14.1, p = 0.0258) and the platelet–lymphocyte ratio (HR 6.26, 95%CI 2.27–15.9, p = 0.0008) were significant independent factors associated with overall survival. There were no significant independent prognostic factors for recurrence-free survival. Conclusions: Preoperative osteopenia is significantly associated with postoperative survival in patients with ICC undergoing hepatectomy. Full article

Randomized controlled trials (RCTs) form a cornerstone of oncology research by generating evidence about the efficacy of therapies in selected patient populations. However, their implementation is often resource- and cost-intensive, and their generalisability to patients treated in routine practice may be limited. Real-world evidence leverages data collected about patients receiving clinical care in routine practice outside of clinical trial settings and provides opportunities to identify and address gaps in clinical trial evidence. This review outlines the strengths and limitations of real-world and RCT evidence and proposes a framework for the complementary use of the two bodies of evidence to advance cancer research. There are challenges to the implementation of real-world research in oncology, including heterogeneity of data sources, timely access to high-quality data, and concerns about the quality of methods leveraging real-world data, particularly causal inference. Improved understanding of the strengths and limitations of real-world data and ongoing efforts to optimise the conduct of real-world evidence research will improve its reliability, understanding and acceptance, and enable the full potential of real-world evidence to be realised in oncology practice. Full article

Cardiovascular disease (CVD) is one of the most common comorbidities in breast cancer survivors. Recently, the target population and treatment period for aromatase inhibitor (AI) treatment in breast cancer patients has been expanding. However, information on adverse CVD events from the long-term use of AI is still lacking. The aim of this study was to investigate the CVD side effects of AI treatment and to evaluate the changes in lipid profile during AI treatment. A systematic search of PubMed (Medline), EMBASE, and Cochrane Library databases reporting on cardiovascular outcomes or lipid profiles change in adult female breast cancer patients (>19 years old) with AI was performed. The pooled analysis of 25 studies showed that the prevalence rate of any type of cardiovascular disease was 6.08 per 100 persons (95% CI 2.91–10.31). Angina was the most common type of heart-related cardiovascular event accounting for 3.85 per 100 persons, followed by any type of stroke (3.34) and venous thromboembolism (2.95). Ischemic stroke (OR 1.39, 95% CI 1.07–1.81) and myocardial infarction (OR 1.30, 95% CI 0.88–1.93) were more common in AI compared with tamoxifen, whereas the prevalence of venous thromboembolism (OR 0.61, 95% CI 0.37–1) was significantly lower in the AI group. In addition, treatment with AI for 6–12 months showed a decrease in HDL-cholesterol and an increase in LDL-cholesterol and total cholesterol. Various CVDs can occur when using AI, and in particular, the risk of MI and ischemic stroke increases in comparison with the adverse effect of tamoxifen. The occurrence of CVD might be related to the deterioration of the lipid profile after AI treatment. Therefore, a customized individualization strategy considering each patient’s CV risk factors is needed during AI treatment. Full article

Hepatocellular carcinoma (HCC) is the second-most-common cause of cancer death. In recent years, studies have suggested that intestinal microbiota dysregulation is closely related to HCC and can affect the therapeutic efficacy of immune checkpoint inhibitors. However, there are few data on the relationship between altered gut microbiota composition and its potential association in patients with advanced hepatocellular carcinoma. Hence, in this study, we aimed to investigate the gut microbiota profile associated with advanced hepatocarcinoma. In total, 20 patients with advanced hepatocarcinoma and 20 matched healthy participants were recruited. Stool samples were collected for 16S rRNA sequencing to confirm intestinal microbiota dysbiosis. The results showed that the Nseqs index in advanced hepatocarcinoma patients was significantly different compared with that in healthy individuals, while the butyrate-producing bacteria decreased and LPS-producing bacteria increased. Meanwhile, Lactobacillus, Anaerostipes, Fusicatenibacter, Bifidobacterium, and Faecalibacterium were significantly correlated with AFP, ALT, AST, and PIVKA. Our findings characterized the gut microbiota composition of advanced hepatocarcinoma, providing an experimental basis and theoretical support for using microbiota to regulate immunotherapy, achieve potential biomarkers for diagnosis, and improve the effect of clinical treatment for patients with advanced hepatocarcinoma. Full article

Depression is a common and disabling disorder in later life, particularly among people with poor physical health. There are many screening tools available that can be used to examine depressive symptoms; however, not all of them may be appropriate or accurate for older adults with cancer. This pilot study was designed to test the diagnostic performance of two screening tools and their short versions in a cohort of vulnerable (G8 score ≤ 14/17) older patients with cancer undergoing comprehensive geriatric assessment (CGA). The prospective analysis covered 50 vulnerable patients with cancer aged ≥70 years. The diagnostic performance of the Geriatric Depression Scale (GDS)-15, GDS-4, Patient Health Questionnaire (PHQ)-9 and PHQ-2 was compared to the ‘gold standard’ Structured Clinical Interview for DSM-5 Disorders (SCID-5-S) depression module A. The sensitivity and specificity in detecting depressive symptoms were the highest in the case of PHQ-2, with an area under the receiver operating characteristic curve (AUROC) of 92.7%. The AUROC for the 9-item version, PHQ-9, was 90.2%. For the GDS-15 and GDS-4, the AUROC was only 56.2% and 62.0%, respectively. The SCREEN pilot study illustrates the potential benefit of using a shorter screening tool, PHQ-2, to identify older patients with cancer who would benefit from a more in-depth emotional evaluation as part of a CGA. Full article

Approximately 80% of breast cancers are estrogen receptor-positive (ER+), and 68–80% of those occur in premenopausal or perimenopausal women. Since the introduction of tamoxifen for adjuvant endocrine therapy in women with non-metastatic ER+ breast cancer, subsequent trials have demonstrated an oncologic benefit with the addition of ovarian function suppression (OFS) to adjuvant endocrine therapy. Subsequently, therapies to either suppress or ablate ovarian function may be included in the treatment plan for patients that remain premenopausal or perimenopausal after upfront or adjuvant chemotherapy and primary surgery. One strategy for OFS, bilateral salpingo-oophorectomy (BSO), has lasting implications, and the routine recommendation for this strategy warrants a critical analysis in this population. The following is a narrative review of the utility of ovarian suppression or ablation (through either bilateral oophorectomy or radiation) in the context of adjuvant endocrine therapy, including selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs). The long-term sequelae of bilateral oophorectomy include cardiovascular and bone density morbidity along with sexual dysfunction, negatively impacting overall quality of life. As gynecologists are the providers consulted to perform bilateral oophorectomies in this population, careful consideration of each patient’s oncologic prognosis, cardiovascular risk, and psychosocial factors should be included in the preoperative assessment to assist in shared decision-making and prevent the lifelong adverse effects that may result from overtreatment. Full article

Objective: To explore the clinicopathological features of solitary fibrous tumors (SFTs) of the lung. Methods: We collected the clinical data of 52 patients with SFTs of the lung confirmed by pathology, and summarized the clinical, radiological, and morphological features, the immunophenotypes, and the prognosis of SFTs. Results: Fifty-two cases of SFTs of the lung were enrolled in this study, including 51 cases of borderline and 1 case of malignancy, 22 males and 30 females. The average onset age was 52.7 years. The lower lobe of the left lung was the preferred site of SFTs, accounting for 30.77% (16/52). Chest CT showed regular and well-demarcated soft tissue density mass, and the tumor size of most cases (46/52, 88.46%) was 1–10 cm. Morphological features: The distribution of tumor cells showed sparse and dense areas. Tumor cells were spindle-shaped, in whorls or hemangiopericytoma-like conformation. Atypia, mitotic figures, and necrosis were found. Immunohistochemistry showed positive expression of CD34, STAT6, Vimentin, BCL2, and CD99. Ki-67 was ≤ 5% in borderline SFTs and > 20% in a malignant SFT. Conclusions: Solitary fibrous tumors of the lung occur more frequently in middle-aged and elderly people, and there is no significant difference in gender. The lower lobe of the left lung is the preferred site of SFTs. The size of most SFTs is 1–10 cm. Chest CT shows morphologically regular and well-demarcated soft tissue density mass. Pathologically, SFTs of the lung are mostly borderline and occasionally malignant. Immunohistochemistry shows the positive expression of CD34, STAT6, Vimentin, BCL2, and CD99. Full article

Drug pricing methods vary extensively across countries. Japan calculates drug prices using cost accounting and based on the efficacy of similar drugs. This study investigated the relationship between drug prices and their clinical efficacy and usefulness using public information on anticancer drugs reimbursed by the National Health Insurance price listing between January 2009 and March 2020. We investigated drug characteristics, prices, and clinical benefits based on overall survival (OS) and progression-free survival (PFS). Eighty anticancer drugs were approved in Japan during the study period. The largest number (28 drugs, 35.0%) was approved based on PFS, 18 (22.5%) were approved based on OS, and 13 (16.3%) based on the response rate. The mean (±SD) drug price was JPY 88,416.2 (±148,974.7), while the median drug price (with quartiles) was JPY 21,694 (JPY 4855.0–JPY 93,396.8). Drug prices were significantly higher for PFS than for OS, while cost index—the drug price to extend PFS or OS by one day—did not differ significantly between PFS and OS. The relationship between the 46 drugs approved based on OS or PFS and their prices was examined. A correlation was found between drug prices and their clinical usefulness in terms of OS but not PFS. Full article

The healthcare workforce plays a pivotal role in cancer care delivery, leadership, policy, education, and research in complex cancer systems. To ensure quality and relevance, health professionals must have the necessary competencies to deliver patient-centered and efficient care, coupled with the ability to work in teams and manage health resources wisely. This paper aims to review the concept of competency-based medical education (CBME) in the context of oncology to provide insights and guidance for those interested in adopting or adapting competency-based education in training programs. The results of a scoping review of CBME in oncology are presented here to describe the current status of CBME in oncology. The literature describing the implementation and evaluation of CBME in oncology training programs for medical professionals internationally is summarized and key themes identified to provide practical guidance for educators. Further, the paper identifies critical competencies for oncology education and training globally and presents recommendations and opportunities for collaboration in competency-based education and training in oncology. The authors argue for increased global collaboration and networking in the realm of CBME to facilitate the establishment of a competent global cancer care workforce. Full article

Marginal zone lymphomas (MZL) are a rare, heterogenous group of lymphomas, accounting for 5–17% of indolent non-Hodgkin lymphomas in the western world. They can be further divided into three subtypes: extranodal MZL, splenic MZL, and nodal MZL. These subtypes differ in clinical presentation and behavior, which influences how they are managed. There is currently no standard of care for the treatment of MZL, owing to the difficulty in conducting phase 3 randomized trials in MZL, and the fact that there are limited data on the efficacy of therapy in individual subtypes. Treatment practices are thus largely borrowed from other indolent lymphomas and are based on patient and disease characteristics, as well as access to therapy. This review summarizes the Canadian treatment landscape for MZL and how these therapies may be sequenced in practice. Full article

Caregivers providing care for their family members with oral cancer usually endure the caregiving burden in silence, which affects their quality of life and necessitates the need for supportive care. The aim of this study is to determine the relationship between the quality of life (QOL) of oral cancer caregivers and their supportive care needs (SCN) in Malaysia. The Malaysian versions of the Caregiver Oncology Quality of Life Questionnaire (M-CarGOQoL) and the Comprehensive Needs Assessment Tool for Cancer Caregivers (M-CNAT-C) were self-administered by 56 family caregivers of oral cancer patients from five tertiary hospitals throughout Peninsular Malaysia and Sarawak between October and December 2021. Correlation and multiple regression analyses were employed, and the significance level was set at p < 0.05. The mean score for the QOL of caregivers was 76.16 ± 16.01, with the lowest scores in the psychological well-being (64.87 ± 30.12) and self-esteem (68.64 ± 28.29) domains. The mean score for SCN of caregivers was 36.42 ± 24.16, with the highest scores in the healthcare staff (58.44 ± 33.80) and information (55.35 ± 29.98) domains. The correlation between QOL and SCN was moderately inversed, (r(54) = 0.58, p < 0.01). There was a significant effect of caregiving duration (<3 h/day versus >3 h/day) on the combined dependent variables (QOL and SCN), F(2, 53) = 5.006, p < 0.01, partial η² = 0.16. QOL and caregiving duration accounted for a significant 43% of SCN, R² = 0.43, adjusted R² = 0.41, F(2, 53) = 20.32, p < 0.01. In conclusion, oral cancer caregivers with poorer QOL have higher SCN. It is recommended that oral cancer caregivers be recognized by healthcare providers in order to deliver holistic patient care. Full article

Improvements in early screening and treatment have contributed to the growth of the number of cancer survivors. Understanding and mitigating the adverse psychosocial, functional, and economic outcomes they experience is critical. Social wellbeing refers to the quality of the relationship with partners/spouses, children, or significant others. Close relationships contribute to quality of life and self-management; however, limited literature exists about social wellbeing during survivorship. This study examined positive and negative self-reported changes in a community sample of 505 cancer survivors. Fourteen items assessed changes in communication, closeness with partner/children, stability of the relationship, and caregiving burden. An exploratory factor analysis was conducted using a robust weighted least square procedure. Differences by sociodemographic and clinical characteristics were investigated. Respondents were mostly male, non-Hispanic white, and ≥4 years since diagnosis. Two factors, labeled Relationship Closeness and Ambivalence, emerged from the analysis. Women, younger survivors, individuals from minority groups, and those with lower income experienced greater negative changes in social wellbeing. Variations by treatment status, time since diagnosis, and institution were also reported. This contribution identifies groups of cancer survivors experiencing affected social wellbeing. Results emphasize the need to develop interventions sustaining the quality of interpersonal relationships to promote long-term outcomes. Full article

Background: The high recurrence rate of hepatocellular carcinoma (HCC) after hepatectomy usually results in poor prognosis. To the best of our knowledge, no study has reported the efficacy of immune checkpoint inhibitors (ICIs) plus targeted therapies on preventing HCC recurrence after hepatectomy. Thus, the aim of this study was to investigate the benefits and safety of applying adjuvant ICIs plus targeted therapies after hepatectomy for patients at high risk of HCC recurrence. Methods: A total of 196 patients with any risk factors for recurrence who underwent hepatectomy for HCC were reviewed in this retrospective study. Results: Compared with the control group (n = 158), ICIs plus targeted therapies (n = 38) had a significantly higher recurrence-free survival (RFS) rate in univariate analysis (HR, 0.46; 95% confidence interval [CI], 0.24–0.90; p = 0.020), multivariate analysis (adjusted HR, 0.62; 95%CI, 0.49–0.79; p < 0.001) and propensity score-matched analysis (HR, 0.35; 95%CI, 0.16–0.75; p = 0.005). Subgroup analyses also showed that postoperative adjuvant ICIs plus targeted therapies might reduce HCC recurrence in patients with the most of risk factors. Conclusion: Postoperative adjuvant ICI plus targeted therapies may reduces early HCC recurrence in patients with a high risk of recurrence, and the treatments are well tolerated. Full article

Currently, the active surveillance of men with favorable intermediate-risk localized prostate cancer (PCa) is a longstanding controversy, in terms of their oncological outcomes, and radical prostatectomy would constitute a similar concern of overtreatment, regarding its functional outcomes. Thus, focal therapy could be considered in men belonging to favorable intermediate-risk group. Among all focal therapies, high-intensity focused ultrasound (HIFU) was the most studied methodology in clinical trials. Although HIFU provided better functional outcomes than radical prostatecomy, the oncological outcomes were inferior in men with intermediate-risk localized PCa. Two articles have been published discussing the feasibility and clinical outcomes of robot-assisted partial prostatectomy (RAPP), and both the functional and oncological outcomes were superior than those with HIFU. However, the rate of positive surgical margins (PSMs) was reported as high in the literature. Here, we present a case of favorable intermediate-risk localized PCa with an isolated tumor at the anterior apex. After reconstructing a personal three-dimensional (3D) image, we utilized it in a 3D image-guided precise excise, followed by intraoperative frozen specimen review. We found that this method may present a resolution to the high PSM rate documented in the current literature regarding RAPP. This method merits further study with a well-designed prospective study. Full article