Current Oncology

DNA methylation is a fundamental mechanism of epigenetic control in cells and its dysregulation is strongly implicated in cancer development. Cancers possess an extensively hypomethylated genome with focal regions of hypermethylation at CPG islands. Due to the highly conserved nature of cancer-specific methylation, its detection in cell-free DNA in plasma using liquid biopsies constitutes an area of interest in biomarker research. The advent of next-generation sequencing and newer computational technologies have allowed for the development of diagnostic and prognostic biomarkers that utilize methylation profiling to diagnose disease and stratify risk. Methylome-based predictive biomarkers can determine the response to anti-cancer therapy. An additional emerging application of these biomarkers is in minimal residual disease monitoring. Several key challenges need to be addressed before cfDNA-based methylation biomarkers become fully integrated into practice. The first relates to the biology and stability of cfDNA. The second concerns the clinical validity and generalizability of methylation-based assays, many of which are cancer type-specific. The third involves their practicability, which is a stumbling block for translating technologies from bench to clinic. Future work on developing pan-cancer assays with their respective validities confirmed using well-designed, prospective clinical trials is crucial in pushing for the greater use of these tools in oncology. Full article

Objective: We investigated the potential relationship between endometriosis and risk of ovarian, endometrial, cervical, and breast cancers using the National Inpatient Sample (NIS) database. Methods: We utilized the International Classification of Diseases (ICD-10) system to identify relevant codes from the NIS database (2016–2019). Univariate and multivariate regression analyses (adjusted for age, race, hospital region, hospital teaching status, income Zip score, smoking, alcohol use, and hormonal replacement therapy) were conducted to evaluate the association between endometriosis and gynecologic cancers and summarized as odds ratios (ORs) with 95% confidence intervals (CIs). Results: In the examined dataset, there were 1164 and 225,323 gynecologic cancer patients with and without endometriosis, respectively. Univariate analysis showed endometriosis was significantly associated with a higher risk of ovarian (OR = 3.42, 95% CI: 3.05–3.84, p < 0.001) and endometrial (OR = 3.35, 95% CI: 2.97–3.79, p < 0.001) cancers. There was no significant association between endometriosis and cervical cancer (OR = 1.05, 95% CI: 0.85–1.28, p = 0.663). Interestingly, endometriosis was significantly associated with a low risk of breast cancer (OR = 0.12, 95% CI: 0.10–0.17, p < 0.001). Multivariate analysis after Bonferroni correction (p < 0.006) showed that endometriosis was significantly associated with a high risk of ovarian (adjusted OR = 3.34, 95% CI: 2.97–3.75, p < 0.001) and endometrial (adjusted OR = 3.61, 95% CI: 3.12–4.08, p < 0.001) cancers. Conversely, there was no significant association between endometriosis and cervical cancer (OR = 0.80, 95% CI: 0.65–0.99, p = 0.036). Conclusions: Patients with endometriosis exhibited unique gynecologic cancer risk profiles, with higher risks for ovarian and endometrial cancers, and no significant risk for cervical cancer. The observed connection between endometriosis and a reduced risk of breast cancer remains a perplexing phenomenon, which cannot be put into context to date. Full article

Background: Many people want to die at home, but it is often not possible because they do not share their wishes with family members. This study was conducted to find out the extent to which patients with advanced urological malignancies had wishes regarding their final stage of life, made arrangements accordingly, and communicated their wishes to relatives and health care professionals. Methods: We conducted a survey among advanced urological tumor patients during their clinic visit at a German university hospital using a 31-item questionnaire. Inclusion criteria were metastatic or irresectable prostate cancer, urothelial carcinoma, or renal cell carcinoma. Results: In total, 88 patients (76 male, 12 female) completed the questionnaire, and 62 of those respondents (70%) had received their tumor diagnosis within the past 5 years. Symptoms were reported by 80%, and 18% described five or more symptoms. The majority (88%) stated that they had thought about their preferred place of death but 58% had not informed anyone about it. The preference for a hospice as the place of death correlated statistically significantly with the absence of a domestic partnership (p = 0.001) or marriage (p < 0.001) and with a high number of symptoms (≥5; p = 0.009). However, 73% had not talked with their urological oncologist about care options in case their health deteriorated though 36% of those were interested in having a conversation about it. Conclusions: Our results showed that 9 out of 10 patients reflected on their preferred place of death but only a few discussed it with anyone. Based on this finding, physicians and healthcare staff should initiate discussions about early care planning so that patients in incurable situations can express their wishes regarding their preferred place of death. Full article

The prognosis of early non-small-cell lung cancer (eNSCLC) remains poor. An understanding of current therapies and outcomes can provide insights into how novel therapies can be integrated into clinics. We conducted a large, retrospective, population-based cohort study of patients with de novo eNSCLC (stages IB, IIA, IIB, and IIIA) diagnosed in Alberta, Canada, between 2010 and 2019. The primary objectives were to describe treatment patterns and survival outcomes among patients with eNSCLC. A total of 5126 patients with eNSCLC were included. A total of 45.3% of patients were referred to a medical oncologist, ranging from 23.7% in stage IB to 58.3% in IIIA. A total of 23.6% of patients initiated systemic therapy (ST), ranging from 3.5% in stage IB to 38.5% in IIIA. For stage IIB and IIIA individuals who received surgery, adjuvant ST was associated with a decreased likelihood of death (hazard ratios (HR) of 0.77 (95% CI: 0.56–1.07) and 0.69 (95% CI: 0.54–0.89), respectively). In a Canadian real-world setting, stage IIB and IIIA patients who received adjuvant ST tended to have better survival than patients who did not, but future studies that provide adjustment of additional confounders are warranted. Examining referral pathways that account for disparities based on age, sex, and comorbidities in the real world would also provide further insights. Full article

The COVID-19 pandemic precipitated drastic changes in cancer care. Its impact on the U.S. head and neck cancer population has yet to be fully understood. This study aims to understand the impact of pandemic-related changes on the head and neck cancer population. An observational study of head and neck cancer patients at a single institution during the spring of 2020 and 2019 was performed. Clinical characteristics and survival outcomes were analyzed. In 2020, 54 head and neck cancer patients were evaluated in the department of radiation oncology vs. 74 patients seen in 2019; 42% of the patients were female in 2019 versus 24% in 2020 (p = 0.036). The median follow-up time was 19.4 and 31 months for 2020 and 2019, respectively. After adjusting for stage, the relapse-free survival probability at 6 and 12 months was 79% and 69% in 2020 vs. 96% and 89% in 2019, respectively (p = 0.036). There was no significant difference in the overall survival, with 94% and 89% in 2020 and 2019, respectively (p = 0.61). Twenty-one percent of patients received induction chemotherapy in 2020 versus 5% in 2019 (p = 0.011); significantly more treatment incompletions occurred in 2020, 9% vs. 0% in 2019 (p = 0.012). Moreover, the stage-adjusted RFS differed between cohorts, suggesting head and neck cancer patients seen during the initial wave of COVID-19 may experience worse oncologic outcomes. Full article

Background: little is known about the incidence and characteristics of multisystem immune-related adverse events (irAEs) associated with dual-agent ipilimumab and nivolumab use. Methods: A retrospective cohort review was completed that included cancer patients seen at the Juravinski Cancer Centre who received at least one dose of ipilimumab and nivolumab from 2018 to 2022. Patient characteristics, cancer types, and irAEs were recorded. Multivariate logistic and cox regressions were completed, comparing those who developed multisystem irAEs, single irAE, and no irAE. Results: A total of 123 patients were included in this study. Out of 123 patients, 72 (59%) had melanoma, 50/123 (41%) had renal cell carcinoma (RCC), and 1/123 (1%) had breast cancer. Multisystem irAEs were seen in 40% of the overall cohort. The most common irAE type was dermatitis (22%), followed by colitis (19%) and hepatitis (17%). Conclusions: Our study demonstrated that multisystem irAEs are prevalent amongst patients receiving ipilimumab and nivolumab. It is important for both physician education and the counseling and consent of patients to monitor the potential for multiple irAEs. Full article

The aim of this informative review was to investigate the application of radiomics in cancer imaging and to summarize the results of recent studies to support oncological imaging with particular attention to breast cancer, rectal cancer and primitive and secondary liver cancer. This review also aims to provide the main findings, challenges and limitations of the current methodologies. Clinical studies published in the last four years (2019–2022) were included in this review. Among the 19 studies analyzed, none assessed the differences between scanners and vendor-dependent characteristics, collected images of individuals at additional points in time, performed calibration statistics, represented a prospective study performed and registered in a study database, conducted a cost-effectiveness analysis, reported on the cost-effectiveness of the clinical application, or performed multivariable analysis with also non-radiomics features. Seven studies reached a high radiomic quality score (RQS), and seventeen earned additional points by using validation steps considering two datasets from two distinct institutes and open science and data domains (radiomics features calculated on a set of representative ROIs are open source). The potential of radiomics is increasingly establishing itself, even if there are still several aspects to be evaluated before the passage of radiomics into routine clinical practice. There are several challenges, including the need for standardization across all stages of the workflow and the potential for cross-site validation using real-world heterogeneous datasets. Moreover, multiple centers and prospective radiomics studies with more samples that add inter-scanner differences and vendor-dependent characteristics will be needed in the future, as well as the collecting of images of individuals at additional time points, the reporting of calibration statistics and the performing of prospective studies registered in a study database. Full article

The aim of this study was to explore the outcomes of pelvic reconstruction with a rectus abdominis myocutaneous (RAM) or rectus abdominis myoperitoneal (RAMP) flap following radical surgery for gynecologic malignancy. This is a retrospective case series of all pelvic reconstructions with RAM or RAMP flap performed in a gynecologic oncology service between 1998 and 2023. Reconstructions with other flaps were excluded. A total of 28 patients were included. Most patients had vulvar cancer (n = 15, 53.6%) and the majority had disease recurrence (n = 20, 71.4%). Exenteration was the most common procedure, being carried out in 20 (71.4%) patients. Pelvic reconstruction was carried out with a RAM flap in 24 (85.7%) cases and a RAMP flap in 4 (14.3%) cases. Flap-specific complications included cellulitis (14.3%), partial breakdown (17.9%), and necrosis (17.9%). Donor site complications included surgical site infection and necrosis occurring in seven (25.0%) and three (10.7%) patients, respectively. Neovaginal reconstruction was performed in 14 patients. Out of those, two (14.3%) had neovaginal stenosis and three (21.4%) had rectovaginal fistula. In total, 50% of patients were disease-free at the time of the last follow up. In conclusion, pelvic reconstruction with RAM/RAMP flaps, at the time of radical surgery for gynecologic cancer, is an uncommon procedure. In our case series, we had a significant complication rate with the most common being infection and necrosis. The development of a team approach, with input from services including Gynecologic Oncology and Plastic Surgery should be developed to decrease post-operative complications and improve patient outcomes. Full article

Purpose: Radiotherapy is integral in the management of hematological malignancies (HM). Standard radiotherapy dose fractionation regimens range between 20 and 50 Gy in 10–25 fractions over 2–5 weeks. This study presents the outcomes of patients with HM treated with hypofractionation radiotherapy (HFRT) during the COVID-19 pandemic. Methods: Patients (n = 36) were treated with HFRT between January 2020 and September 2022. The outcomes measured were the overall response rate (ORR), freedom from local progression (FFLP), and overall survival (OS). Results: The median follow-up was 13.2 months. Thirty-three patients (92%) had non-Hodgkin (NHL) or Hodgkin lymphoma (HL). Eighteen patients (50%) had aggressive and nine (25%) had indolent NHL. Nineteen patients (53%) presented with stage I/II and fifteen (42%) with stage III/IV disease. Twenty-five (69.4%) and eleven (30%) received consolidative and definitive RT, respectively. Twenty patients (56%) received treatment to the neck and/or thorax and nine (25%) to the abdomen or pelvis. The total dose ranged from 18 to 42.5 Gy in 6–17 fractions/2.67–5 Gy per fraction. The median dose in 2 Gy fractions for an alpha/beta (α/β) ratio of 10 amounted to 39 Gy (SD ± 13.86) and 43.6 Gy (SD ± 12) for an α/β of 3. The most commonly used fractionation scheme was 39 Gy in 13 fractions. ORR was 94.4% for the entire cohort, and 100, 94.4, and 83.3% for indolent NHL, aggressive NHL, and HL patients. The two-year FFLP was 76% (95% CI: 34–93%) for the entire cohort and 100, 87 (95% CI: 56.4–96.5%), and 42% (95% CI: 1.1–84.3%) for the indolent NHL, aggressive NHL, and HL patients. Two-year OS for the entire cohort was 80% (95% CI: 59.9–90.5%) and 100, 66.1 (95% CI: 36.4–84.4%), and 100% for the indolent NHL, aggressive NHL, and HL patients. Only one patient presented with grade two pulmonary toxicity. Conclusions: HFRT in HM provides excellent local control to be validated in a larger prospective study. Full article

Local and metastatic recurrence are primary concerns following the treatment of locally advanced rectal cancer (LARC). Chemoradiation (CRT) can reduce the local recurrence rates and has subsequently moved to the neoadjuvant setting from the adjuvant setting. Pathological complete response (pCR) rates have also been noted to be greater in patients treated with neoadjuvant CRT prior to surgery. The standard approach to treating LARC would often involve CRT followed by surgery and optional adjuvant chemotherapy and remained the treatment paradigm for almost two decades. However, patients were often unable to complete adjuvant chemotherapy due to a decreased tolerance of chemotherapy following surgery, which led to upfront treatment with both CRT and chemotherapy, and total neoadjuvant therapy, or TNT, was created. The efficacy outcomes of local recurrence, disease-free survival, and pCR have improved in patients receiving TNT compared to the standard approach. Additionally, more recent data suggest a possible improvement in overall survival as well. Patients with a complete clinical response following TNT have the opportunity for watch-and-wait surveillance, allowing some patients to undergo organ preservation. Here, we discuss the clinical trials and studies that led to the adoption of TNT as the standard of care for LARC, with the possibility of watch-and-wait surveillance for patients achieving complete responses. We also review the possibility of overtreating some patients with LARC. Full article

Female BRCA1/2 and PALB2 germline pathogenic variant carriers have an increased lifetime risk of breast cancer and may wish to consider risk-reducing mastectomy (RRM) for surgical prevention. Quantifying the residual lifetime risk and absolute benefit from RRM requires careful consideration of a patient’s age, pathogenic variant, and their personal history of breast or ovarian cancer. Historically, patients have been counselled that RRM does not necessarily prolong survival relative to high-risk surveillance, although recent studies suggest a possible survival benefit of RRM in BRCA1 carriers. The uptake of RRM has increased dramatically over the last several decades yet varies according to sociodemographic factors and geographic region. The increased adoption of nipple-sparing mastectomy techniques, ability to avoid axillary staging, and availability of reconstructive options for most germline pathogenic variant carriers has helped to minimize the morbidity of RRM. Preoperative discussions should include evidence regarding postmastectomy sensation, the potential for supplemental surgery, pregnancy-related chest wall changes, and the need for continued clinical surveillance. Approaches that include sensation preservation and robotic nipple-sparing mastectomy are an area of evolving research that may be more widely adopted in the future. Full article

Amid pandemics, health care teams face unprecedented challenges, requiring significant efforts to sustain optimal functioning and navigate rapid practice changes. It is therefore crucial to identify factors affecting team functioning in these contexts. The present narrative review more specifically summarizes the literature on key elements of cancer teams’ functioning during COVID-19. The search strategy involved four main databases (i.e., Medline OVID, EMBASE, PsycINFO, and CINAHL), as well as Google Scholar, from January 2000 to September 2022. Twenty-three publications were found to be relevant. Each was read thoroughly, and its content summarized. Across publications, three key themes emerged: (1) swiftly adopting virtual technology for communication and interprofessional collaboration, (2) promoting team resilience, and (3) encouraging self-care and optimizing team support. Our findings underscore key team functioning elements to address in future pandemics. More research is needed to document the perspectives of broader-based team members (such as patients and lay carers) to inform more comprehensive evidence-based team functioning guidelines. Full article

Although the disease burden of elderly cancer patients is rapidly increasing, reliable scientific information, value and preference information of domestic patients, and standardized guidelines for determining the treatment of elderly cancer patients are lacking. The aim of this study is to compare the therapeutic effects of radiofrequency ablation (RFA) and surgery in hepatocellular carcinoma (HCC) patients aged 65 years or older. For the meta-analysis, the databases including PubMed (MEDLINE), EMBASE, OVID Medline, and the Cochrane Library were systematically searched. After the abstract-based review by two investigators, selected manuscripts were read in detail. The surgery group showed higher overall survival (OS) (HR 1.44, 95% CI 1.22–1.70) and disease-free survival (DFS) (HR 1.40, 95% CI 1.00–1.97) than the RFA group. This was also shown in small HCC of less than 3 cm (OS, HR 1.42, 95% CI 1.00–2.03; DFS, HR 1.32, 95% CI 0.91–1.91). This might be related to the high local recurrence in the RFA group (OR 4.90, 95% 2.16–11.08). On the other hand, adverse events were significantly lower in the RFA group (OR 0.22, 95% CI 0.14–0.36), which led to a decrease in the duration of hospital stay (mean difference −14.88 days, 95% CI −22.44–−7.32). In elderly HCC patients, survival in the surgery group was significantly higher than in the RFA group, but various complications tended to increase; so, appropriate patient selection is required. Full article

Soft tissue sarcomas (STS) originating from connective tissue rarely affect the lymph nodes. However, involvement of lymph nodes in STS is an important aspect of prognosis and treatment. Currently, there is no consensus on the diagnosis and management of lymph node metastases in STS. The key risk factor for nodal involvement is the histological subtype of sarcoma. Radiological and pathological evaluation seems to be the most effective method of assessing lymph nodes in these neoplasms. Thus, sentinel lymph node biopsy (SLNB), which has been shown to be valuable in the management of melanoma or breast cancer, may also be a beneficial diagnostic option in some high-risk STS subtypes. This review summarizes data on the risk factors and clinical characteristics of lymph node involvement in STS. Possible management and therapeutic options are also discussed. Full article

Cervical cancer is frequently diagnosed in women during their reproductive years, and fertility preservation is an essential part of their cancer treatment. In highly selected patients with early stage, low-risk cervical cancer and a tumor size ≤ 2 cm, several treatment strategies can be offered for patients wishing to preserve fertility, including radical/simple trachelectomy or conization with pelvic lymph node assessment. Trachelectomy can be performed through a vaginal, abdominal, or minimally invasive approach and has been shown to have an equivalent oncologic outcome compared to radical hysterectomy. All surgical approaches for radical trachelectomy seem to have excellent survival with comparable oncologic outcomes. Nevertheless, patients undergoing vaginal trachelectomy have better obstetric outcomes compared to the other routes. In patients with larger tumors (2–4 cm), neoadjuvant chemotherapy followed by fertility-sparing surgery is an alternative option. Several chemotherapy regimens have been used for this indication, with a pathologic complete response rate of 17–73%. For locally advanced diseases that require radical hysterectomy or primary chemoradiation, fertility preservation can be performed using oocyte, embryo, or ovarian tissue cryopreservation, as well as ovarian transposition. For these patients, future pregnancy is possible through surrogacy. In addition to fertility preservation, ovarian transposition, where the ovaries are repositioned outside of the radiation field, is performed to maintain ovarian hormonal function and prevent premature ovarian failure. In summary, fertility-preservation treatment strategies for patients with early stage cervical cancer are continuously evolving, and less radical surgeries are becoming more acceptable. Additional and ongoing evidence is helping determine the impact of conservative procedures on oncologic and obstetric outcomes in these patients. Full article

Colorectal cancer is a common disease, both in Chile and worldwide. The most widely used chemotherapy schemes are based on 5-fluorouracil (5FU) as the foundational drug (FOLFOX, CapeOX). Genetic polymorphisms have emerged as potential predictive biomarkers of response to chemotherapy, but conclusive evidence is lacking. This study aimed to investigate the role of genetic variants associated with 5FU-based chemotherapy on therapeutic response, considering their interaction with oncogene mutations (KRAS, NRAS, PI3KCA, AKT1, BRAF). In a retrospective cohort of 63 patients diagnosed with metastatic colorectal cancer, a multivariate analysis revealed that liver metastases, DPYD, ABCB1, and MTHFR polymorphisms are independent indicators of poor prognosis, irrespective of oncogene mutations. BRAF wild-type status and high-risk drug-metabolism polymorphisms correlated with a poor prognosis in this Chilean cohort. Additionally, findings from the genomics of drug sensitivity (GDSC) project demonstrated that cell lines with wild-type BRAF have higher IC50 values for 5-FU compared to BRAF-mutated cell lines. In conclusion, the genetic polymorphisms DPYDrs1801265, ABCB1rs1045642, and MTHFRrs180113 may serve as useful biomarkers for predicting a poor prognosis in patients undergoing 5-fluorouracil chemotherapy, regardless of oncogene mutations. Full article

Immune checkpoint inhibitors (ICI) have significantly improved outcomes in advanced non-small cell lung cancer (NSCLC). We evaluated the effect of opioid use on outcomes in patients receiving ICI either alone or with chemotherapy. We conducted a retrospective review of 209 patients with advanced NSCLC who received an ICI at the University of Virginia between 1 February 2015 and 1 January 2020. We performed univariate and multivariate analyses to evaluate the impact of opioid use on duration of therapy (DOT) and overall survival (OS). Patients with no or low opioid use (n = 172) had a median DOT of 12.2 months (95% CI: 6.9–17.4) compared to 1.9 months (95% CI: 1.8–2.0) for those with high opioid use (n = 37, HR 0.26 95% CI: 0.17–0.40, p < 0.001). Patients with no or low opioid use had a median OS of 22.6 months (95% CI: 14.8–30.4) compared to 3.8 months (95% CI: 2.7–4.9) for those with high opioid use (HR 0.26 95% CI: 0.17–0.40 p < 0.001). High opioid use was associated with a shorter DOT and worse OS. This difference remained significant when accounting for possible confounding variables. These data warrant investigation of possible mechanistic interactions between opioids, tumor progression, and ICIs, as well as prospective evaluation of opioid-sparing pain management strategies, where possible. Full article

Objective: We aimed to evaluate the use of CDK4/6 inhibitors as a risk factor for medication-related osteonecrosis of the jaw (MRONJ) in a cohort of patients with metastatic breast cancer treated with denosumab. Methods: This was a multicentre, retrospective, observational study. All patients with breast cancer treated with denosumab (January 2011–December 2022) were included. The relationship between CDK4/6 inhibitors and MRONJ was analysed. Results: A total of 243 patients were included, ninety-five (44.2%) of whom used a CDK4/6 inhibitor. There were 21 patients with MRONJ. In patients treated with denosumab without CDK4/6 inhibitors, the incidence of MRONJ and mean time to the occurrence of MRONJ were 6.6% (8/120) and 16.8 months (SD 7.8), respectively; in patients treated with denosumab and CDK4/6 inhibitor, these values were 13.7% (13/95) and 15.4 months (SD 8.7), respectively. The difference in the incidence was not significant (p = 0.085). Among the 19 patients who used abemaciclib, the probability of MRONJ occurrence was significantly higher compared to patients not using CDK4/6 inhibitors (p = 0.0178). Conclusions: These results suggest that the incidence of MRONJ in patients with metastatic breast cancer treated with denosumab is higher, and the onset of MRONJ occurs earlier in the presence of CDK4/6 inhibitors. The differences were statistically significant in the patients who used abemaciclib. Given that the use of this combination is very common in routine clinical practice, it would be advisable to carry out larger prospective studies to clarify the risk of this association. Full article

High-grade serous ovarian cancer (HGSOC) is one of the most lethal tumors generally and the most fatal cancer of the female genital tract. The approved standard therapy consists of surgical cytoreduction and platinum/taxane-based chemotherapy, and of targeted therapy in selected patients. The main therapeutic problem is chemoresistance of recurrent and metastatic HGSOC tumors which results in low survival in the group of FIGO III/IV. Therefore, the prediction and monitoring of chemoresistance seems to be of utmost importance for the improvement of HGSOC management. This type of cancer has genetic heterogeneity with several subtypes being characterized by diverse gene signatures and disturbed peculiar epigenetic regulation. HGSOC develops and metastasizes preferentially in the specific intraperitoneal environment composed mainly of fibroblasts, adipocytes, and immune cells. Different HGSOC subtypes could be sensitive to distinct sets of drugs. Moreover, primary, metastatic, and recurrent tumors are characterized by an individual biology, and thus diverse drug responsibility. Without a precise identification of the tumor and its microenvironment, effective treatment seems to be elusive. This paper reviews tumor-derived genomic, mutational, cellular, and epigenetic biomarkers of HGSOC drug resistance, as well as tumor microenvironment-derived biomarkers of chemoresistance, and discusses their possible use in the novel complex approach to ovarian cancer therapy and monitoring. Full article