Environmental carcinogenesis is traditionally explained by the accumulation of genetic alterations induced by exogenous carcinogens. However, most exposed cells do not undergo malignant transformation because intrinsic tumor-suppressive mechanisms limit the expansion of damaged clones. Among these mechanisms, cellular senescence represents a major barrier that restricts proliferation following DNA damage, oncogenic stress, and other carcinogen-induced insults. In this review, we examine environmental carcinogenesis within a probabilistic evolutionary framework in which tumor initiation depends not only on mutation acquisition but also on the ability of rare cells to evade senescence-mediated growth arrest. Environmental carcinogens contribute to cancer development by increasing genomic instability, altering tissue microenvironments, and modifying selective pressures, whereas senescence acts as a critical constraint on clonal evolution. We further discuss how aging, immune surveillance, DNA-repair capacity, and tissue-specific factors influence the likelihood of senescence escape and malignant progression. This integrative perspective highlights carcinogenesis as a multistep stochastic process shaped by the interaction between mutational events, cellular fitness barriers, and microenvironmental selection. Understanding how these factors collectively regulate transformation may improve mechanistic models of cancer risk and identify new opportunities for prevention and early intervention.

Immunity plays critical roles in cutaneous melanoma. We investigated the association between the pro-inflammatory interleukin-1β gene (IL-1B) rs16944 (-511 C > T) promoter single nucleotide polymorphism (SNP) and cutaneous melanoma susceptibility and clinical features. This observational case-control study included 133 patients with cutaneous melanoma and 900 healthy controls from Northeastern Italy. The rs16944 C > T polymorphism was determined by genomic DNA restriction fragment analysis. The IL-1B rs16944 C allele (OR = 1.44, p = 0.014) and CC genotype (OR = 1.48, p = 0.037) were associated with modestly higher odds of melanoma. Among melanoma patients, the CC genotype was associated with Stage I disease (OR = 2.45, p = 0.016) and Breslow thickness ≤ 0.75 mm (OR = 2.27, p = 0.049), whereas it was less frequent in Stage IV melanoma (OR = 0.37, p = 0.029). The CT genotype was associated with Stage IV melanoma (OR = 3.03, p = 0.014) and with lower-limb (OR = 2.45, p = 0.038) and lower-extremity (OR = 3.09, p = 0.005) melanoma. These divergent associations are exploratory and do not establish disease trajectory or a functional effect of rs16944; mechanistic interpretation remains uncertain because IL-1β expression or activity was not measured in this cohort. To our knowledge, this is the first report of an association between a genetic polymorphism and lower-limb/lower-extremity melanoma. These exploratory findings require confirmation in independent cohorts.

Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL-NT), is a rare and aggressive lymphoma for which real-world data from resource-limited settings remain scarce. This study evaluated the efficacy and safety of frontline multimodal treatment strategies for localized ENKTL-NT.

We retrospectively analyzed 62 patients with localized ENKTL-NT treated at the Vietnam National Cancer Hospital between May 2019 and June 2025. Patients received concurrent chemoradiotherapy followed by VIPD or VIDL, or sequential chemoradiotherapy with GELOX/PGEMOX. Treatment responses, survival outcomes, and toxicities were assessed.

The median age was 44 years, and 67.7% of patients had stage I disease. Baseline EBV-DNA positivity was detected in 46.8%, while 54.8% had PINKE scores of 1-2. The overall response rate was 93.5%, including an 85.5% complete response rate. Grade 3-4 neutropenia was the most common adverse event (18.7%). The estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 76.3% and 79.5%, respectively. Multivariable Cox analysis identified PINKE risk stratification as an independent predictor of both PFS and OS.

Frontline multimodal treatment strategies achieved high response rates, favorable survival outcomes, and manageable toxicities in localized ENKTL-NT. The PINKE score remained an important prognostic factor, supporting risk-adapted treatment selection in routine clinical practice.

Background: Inequitable access to clinical trials persists in blood cancers despite ongoing equity, diversity, and inclusion (EDI) efforts. Despite the critical role of clinical trials in improving survival and outcomes, recruitment remains suboptimal, limiting patient access to potentially life-saving therapies. Practical and scalable approaches are therefore needed to address the non-medical barriers that hinder patient readiness upstream of enrolment. Methods: Myeloma Canada led a national, multi-phase initiative using human-centred design (HCD) to operationalize EDI in clinical trials. Following an initial systems level workshop, the two-day Phase 0 workshop used a HCD approach that convened a purposively selected multidisciplinary group of stakeholders to co-design operational solutions for non-medical barriers affecting trial participation for patients. Given the use of purposive sampling, the results should be interpreted as reflecting a balanced range of diverse, informed perspectives across the Canadian clinical trial ecosystem. Results: Participants identified persistent cultural, logistical, financial, and linguistic barriers, along with fragmented awareness of available supports. Across diverse personas and care settings, all groups independently converged on a human-centred, equity-focused pre-trial navigation model supported by simple digital tools, including AI-enabled infrastructure drawing on curated resources from validated sources with appropriate governance, privacy, and oversight. Digital tools were proposed to support, rather than replace, human support and to align with existing health system realities. Conclusions: This hypothesis-generating work proposes a feasible, sustainable, and scalable equity-embedded, protocol-agnostic navigation framework. Its external hub-and-spoke structure can reduce non-medical barriers, strengthen trial access and accrual, and enhance representativeness. Pilot implementation that assesses feasibility, uptake, workflow impact, equity effects, and implementation burden is warranted.

Background/Objectives: Multiple myeloma (MM) disproportionately affects older adults and racial/ethnic minorities, many of whom face socioeconomic barriers to care. Immunomodulators (IMiDs) are central to MM therapy, but their benefit relies on timely initiation and sustained adherence. In safety-net settings, barriers such as insurance approvals, Patient Medication Assistance Program (PMAP) enrollment, and Risk Evaluation and Mitigation Strategy (REMS) requirements may influence adherence. This study evaluated IMiD adherence during the first two years of therapy among socioeconomically vulnerable MM patients in a large safety-net hospital, with attention to PMAP enrollment and treatment delays. Methods: We conducted a retrospective cohort study of adults (≥18 years) with newly diagnosed MM between October 2010 and January 2022 who initiated lenalidomide or pomalidomide at a safety-net hospital. Adherence was measured using the proportion of days covered (PDC). Delays in initiation were defined as ≥1 month from diagnosis to first IMiD prescription fill. This threshold was selected a priori based on the REMS-mandated 28-day prescription supply limit for lenalidomide and pomalidomide, which establishes a natural monthly treatment cycle; a delay exceeding one full 28-day cycle before therapy initiation is operationally meaningful within the REMS framework. Results: Eighty patients met criteria (mean age 55.1 years; 56.3% Hispanic/Latino; 31.3% African American). Most were unemployed (63.8%), 42.5% uninsured, and 57.5% enrolled in PMAP. Only 12.5% achieved PDC ≥ 80%. Median PDC was higher among PMAP enrollees (0.40 vs. 0.31; p = 0.0293) and transplant-ineligible patients (0.46 vs. 0.27; p = 0.0218). Delays ≥ 1 month occurred in 65% of patients. Conclusions: Adherence to IMiDs was suboptimal in this younger safety-net cohort. Although PMAP improved adherence, program delays may reduce early treatment benefits, underscoring the need for streamlined access and targeted interventions to address both patient- and system-level barriers.

In the companion article in this issue of Current Oncology, 'Management of AML in Older Patients: An Updated Canadian Consensus', the authors have presented the third iteration of Canadian consensus guidelines on AML treatment in the elderly. While many aspects of AML treatment in the elderly have become better defined, some old questions remain and new questions and controversies have arisen. Here, we address three topics on which there is, at this time, no universal consensus. The first is the development and features of new risk-stratification systems specifically aimed at older, less-intensively treated patients. Several different systems now exist in parallel, potentially causing confusion amongst clinicians. The second topic is good-prognosis AML subtypes (IDH1- and NPM1-mutated AML). In the Canadian context, IDH1-mutated AML is of particular interest due to the new availability of ivosidenib in Canada. The third topic is adverse-risk AML subtypes (FLT3- and TP53-mutated AML). FLT3-mutated AML remains problematic, although it is anticipated that new drug approvals and measurable residual disease-based treatment approaches may alleviate this, at least in part. And in particular, TP53-mutated AML remains a major problem. Ongoing clinical trial enrollment is essential.

Lymphovascular space invasion (LVSI) is a well-established prognostic factor in endometrial cancer; however, its independent contribution to para-aortic nodal metastasis remains incompletely defined. Identifying factors associated with nodal dissemination is important for surgical staging and postoperative management. This retrospective, single-center cohort study included 121 patients with endometrial cancer who underwent laparoscopic pelvic and para-aortic lymphadenectomy. The cohort was predominantly obese (median BMI: 32 kg/m²). Clinicopathological variables were analyzed using univariable and multivariable logistic regression models to identify associations with lymph node metastasis and para-aortic lymph node metastasis. Lymph node metastasis was observed in 16.5% of patients, including para-aortic involvement in 9.9%. In univariable analysis, the LVSI category was significantly associated with lymph node metastasis (p = 0.002), with substantial LVSI being present in 50.0% of patients with nodal metastasis compared with 14.9% of those without. LVSI was categorized as negative, focal, or substantial. In multivariable logistic regression analyses using negative LVSI as the reference category, substantial LVSI remained independently associated with both overall nodal metastasis (OR 5.44, 95% CI 1.67-17.65, p = 0.005) and para-aortic nodal metastasis (OR 6.98, 95% CI 1.81-26.78, p = 0.005), whereas focal LVSI was not significantly associated with either outcome. These findings suggest that the extent of LVSI may be relevant to nodal metastasis, with substantial LVSI showing a stronger association than focal LVSI.

The study aims to investigate the Health-Related Quality of Life (HRQOL) in lung cancer survivors, comparing it with the HRQOL of survivors of other types of cancer, analyzing its association with clinically significant distress, and exploring the modulating role of sociodemographic, clinical, and psychosocial variables. A total of 141 lung cancer survivors who had completed treatment with curative intent and were disease-free completed the Quality of Life in Adult Cancer Survivors questionnaire (QLACS), the Brief Symptom Inventory-18 (BSI-18), the Medical Outcomes Study-Social Support Survey (MOS-SSS), and the Utrecht Proactive Coping Competence scale (UPCC). Several multivariate analyses of variance (MANOVA) were performed to address the study objectives. Statistical analysis was performed using IBM SPSS Statistics 22.0. The overall HRQOL of lung cancer survivors did not differ from the HRQOL of hematologic, breast, and gynaecologic cancer survivors and was lower than that of colorectal, head/neck, prostate, and melanoma cancer survivors. HRQOL was associated with clinically significant distress. Younger age, female sex, lower levels of proactive coping, and less positive social interaction were independently associated with worse HRQOL in lung cancer survivors. The overall HRQOL of lung cancer survivors is among those with the poorest HRQOL compared with other cancer survivors' groups. The modifiable nature of the psychosocial variables that characterize the risk profile (with the exception of sociodemographic ones) allows for the establishment of more ambitious goals than the simple establishment of subgroups on which to prioritize care. The team of professionals involved in the care of lung cancer survivors should also provide intervention strategies that improve their well-being.

The literature on the qualitative experiences of patients with non-Hodgkin lymphoma (NHL) is limited. Qualitative interviews were conducted to investigate participants' experiences with two types of NHL (diffuse large B-cell lymphoma [n = 20] and mantle cell lymphoma [n = 10]) and evaluate the comprehensiveness of patient-reported outcome (PRO) measures. Fatigue, tiredness, body aches, night sweats, lethargy, headache, appetite loss, altered taste, and weakness were the most frequent and bothersome symptoms. Key impacts were decreased physical performance, restricted activity, sadness, distress, fear of recurrence, and worry about future. Most participants expressed positive opinions about the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) (n = 22/28), EORTC QLQ-NHL-High Grade Module 29 (EORTC QLQ-NHL-HG29) (n = 12/16), EORTC QLQ-NHL-Low Grade Module 20 (EORTC QLQ-NHL-LG20) (n = 8/12), and Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) (n = 10/14), considering them relevant to their experiences (22/27, 13/15, 9/13, and 10/12, respectively). All measures adequately captured their experiences with NHL (QLQ-C30: n = 26/26, NHL-HG29: n = 14/14, NHL-LG20: n = 11/11, and FACT-Lym: n = 12/13). These findings provide a valuable framework for informing the selection of appropriate PRO measures in NHL clinical trials and identifying potentially meaningful trial endpoints.

After radical hysterectomy for cervical cancer, postoperative bladder dysfunction is common. This randomized controlled trial evaluated whether adjunctive transcutaneous electrical acupoint stimulation (TEAS) reduces urinary retention. A total of 108 patients were assigned to a control group (standard bladder training, n = 53) or a TEAS group (standard training plus daily 30 min TEAS for 7 days from postoperative day 3, n = 55). The primary outcome was urinary retention (post-void residual > 100 mL on day 11). Secondary outcomes included residual volume, recovery time, recatheterization, urinary tract infection (UTI), treatment efficacy, and quality of life (SF-36). Urinary retention occurred in 35.8% of controls versus 23.6% of TEAS patients (p = 0.164). TEAS significantly reduced median residual volume (70 vs. 85 mL, p = 0.004), shortened median recovery time (2 vs. 4 h, p < 0.001), and lowered recatheterization (16.4% vs. 34.0%, p = 0.036). UTI rates were similar. Treatment efficacy favored TEAS (p = 0.009), and all eight SF-36 domains significantly improved (all p < 0.01). In conclusion, adjunctive TEAS did not significantly reduce the primary outcome of urinary retention but significantly improved multiple secondary bladder-emptying measures and quality of life after radical hysterectomy for cervical cancer.