Oncologist最新文献

Introduction: Metastatic or locally advanced cutaneous squamous cell carcinomas (CSCC) affect mainly individuals over 75 years of age. Anti-PD1 therapy is the first-line treatment. Limited data are available on the continuation of immunotherapy after complete response (CR) has been achieved.

Materials and methods: We present a retrospective monocentric study of patients over 75 years of age treated with anti-PD1 therapy for CSCC after early immunotherapy discontinuation. Patients were treated between 01/2019 and 01/2024.

Results: We identified 44 patients over 75 years of age treated with anti-PD1 therapy, 14 of whom achieved CR, leading to the discontinuation (31%). Median age was 83.5 years. Tumor were located on the head and neck in 92.9% of cases. Median follow-up was 20 months. Median time to CR was 5 months. Discontinuation occurred 1.3 months after the CR diagnosis. One-third of the patients experienced no adverse events. Only one patient experienced grade 3 toxicity, and 10 months after discontinuation of treatment, experienced a nodal recurrence. One death occurred 8 months after CR and was unrelated to CSCC or treatment.

Conclusion: Anti-PD1 therapy is effective and safe in elderly patients. CR can be achieved quickly and maintained, despite early treatment discontinuation. The use of anti-PD1 therapy is therefore encouraged even in this fragile and comorbid population, with discontinuation planned as soon as a complete response is obtained to limit the duration of treatment and promote quality of life for patients. Further studies and prolonged follow-up are needed to establish guidelines regarding anti-PD1 discontinuation.

Background: Sperm cryopreservation offers male cancer patients a critical opportunity to preserve fertility prior to gonadotoxic therapy, yet utilization of banked sperm remains modest, typically under 10%. A structured understanding of barriers across the cancer survivorship continuum is needed to support patients in utilization of cryopreserved sperm in alignment with their reproductive goals.

Materials and methods: This expert review synthesizes current evidence and clinical experience to explore the multifaceted barriers to cryopreserved sperm use and propose specific solutions. Key intervention timepoints are examined, including the post-treatment fertility return visit, long-term cryopreservation while remote from family building, readiness for family building, and posthumous considerations. We subsequently outline an optimal Oncofertility Patient Care Pathway.

Results: Multiple clinical, psychosocial, and financial obstacles limit the transition from sperm banking to use. Approximately one-third of survivors do not attend post-treatment fertility return visits, reducing opportunities for counseling and longitudinal reproductive planning. Psychological factors-including fear of cancer recurrence and delayed readiness for family building-contribute to prolonged storage. Many patients remain underinformed about the efficacy and processes of assisted reproductive techniques, while financial concerns are significant. These intersecting barriers hinder use of cryopreserved sperm. Opportunities exist to intervene at key timepoints, as outlined in the Oncofertillity Patient Care Pathway.

Conclusion: A multidisciplinary and structured oncofertility pathway, such as detailed in this review, is needed to support cancer survivors in achieving their reproductive goals. Enhanced counseling, technology-enabled follow-up systems, targeted psychological support, and policies promoting broader insurance coverage for assisted reproduction represent key strategies to overcome existing barriers.

Background: Historically, brain metastasis (BM) is associated with poor survival for patients with metastatic renal cell carcinoma (mRCC). The prognostic significance of BM in the immune checkpoint (ICI) era is unclear.

Methods: We performed a retrospective cohort study of patients diagnosed with clear cell RCC (ccRCC) between 2012-2023. We examined the association between BM and overall survival (OS) among patients by treatment type (with or without ICI in any line of therapy) and whether they had brain MRI screening.

Results: We identified 338 patients with metastatic ccRCC between 2012 and 2023, of whom 96 (28.4%) had BM. mOS from the time of metastatic ccRCC diagnosis was 54.3 months (mo) in patients without BM versus 37.3 mo in patients with BM (P = .03). Among patients who received ICI therapy, mOS was 66.4 mo in those without BM versus 37.7 mo in those with BM (P = .01). In patients who did not receive ICI therapy, mOS was 32.1 mo in those without BM versus 17.6 mo in those with BM (P = .4). In those with BM, mOS from the time of initial metastatic disease diagnosis was 86.7 mo for those who underwent MRI brain screening versus 27.9 mo for those who did not (P = .00016).

Conclusion: In our ccRCC population, OS for patients with metastatic ccRCC and brain metastases has improved in the era of ICI therapy. Brain metastases are associated with poor prognosis. Patients with brain metastases discovered on screening had improved overall survival compared to those with brain metastases discovered because of symptoms.

Pseudosarcomatous myofibroblastic proliferation (PMP) is a rare anaplastic lymphoma kinase (ALK), ALK fusion-associated tumor-like lesion that requires differentiation from inflammatory myofibroblastic tumor (IMT). This article reports two cases of bladder ALK fusion-positive PMP: a 16-year-old male achieved partial remission (PR) postoperatively with lorlatinib but experienced memory decline and mood disturbances, which resolved after dose reduction; a 34-year-old female showed significant tumor shrinkage (PR) without severe adverse reactions. The study confirms the marked efficacy of ALK inhibitors in ALK-positive PMP, but highlights the need to monitor neurotoxicity in adolescent patients. Through analysis of the FN1 (Fibronectin 1)-ALK fusion mechanism and literature review, this study emphasizes the importance of pathological differentiation, individualized treatment, and dynamic cognitive monitoring, providing insights for precision therapy in rare diseases.

Purpose: Immune checkpoint inhibitors (ICIs) improve recurrence outcomes in stage III melanoma but can cause immune-related adverse events (irAEs) of varying severity. While some studies suggest irAEs correlate with improved survival, findings remain inconsistent. Optimal management of recurrent stage III melanoma after adjuvant ICI therapy is also unclear. Here, we evaluate the impact of irAEs on survival and describe subsequent treatments in patients with recurrent stage III melanoma.

Patients and methods: We identified 171 patients with stage III melanoma treated with adjuvant ICIs since 2017. Clinical endpoints included overall survival, progression-free survival, distant metastasis-free survival, melanoma-specific survival, and time-to-irAE, which were analyzed using Kaplan-Meier method, Cox model, and Fine-Gray's method. Cox model with time-varying covariate modeling addressed immortal-time bias. Subgroup analysis examined survival by irAE type, grade, and treatment resumption.

Results: irAEs occurred in 43.86% of patients, with dermatitis (17.64%), colitis (16.67%), and hypothyroidism (15.69%) the most common. irAE presence did not impact survival outcomes. Thirty-one grade 3+ irAEs occurred, which were linked to increased short-term melanoma-specific mortality. Immune-related hepatitis was associated with higher mortality risk in multivariable modeling. Recurrence or progression occurred in 28.65% of patients, with 38.78% located at a distal site. Among those who started additional medical treatment, 42.86% received dual-checkpoint inhibitor therapy and 14.29% enrolled in clinical trials.

Conclusion: Our findings do not support an association between irAEs and survival in patients with stage III melanoma. However, specific types of events, particularly hepatitis, may increase mortality. Prospective studies are needed to clarify optimal treatment after recurrence.

Background: Cervical cancer is one of the leading causes of cancer-related deaths among Ethiopian women, despite being largely preventable. Women treated for precancerous cervical lesions remain at elevated risk of developing invasive cancer, yet little is known about the burden and predictors of persistent lesions following treatment in resource-limited settings.

Materials and methods: We conducted a cross-sectional study among 242 women who underwent ablative or excisional therapy for precancerous cervical lesions at 3 clinics in Addis Ababa between November 2022 and December 2023. Data were collected using structured questionnaires and clinical records. Logistic regression analysis was used to identify factors associated with persistent lesions, reported as adjusted odds ratios (AORs) with 95% CIs.

Results: Of the 242 women treated, 104 (43.0%; 95% CI, 37.2-49.6%) experienced persistent lesions within 1 year. Persistent lesion rates were highest among women initially screened with a Pap smear (97.4%) compared to visual inspection with acetic acid (VIA) (21.9%) and HPV DNA testing (14.7%). Independent predictors of persistent lesions included an age of ≥50 years (AOR = 5.4; 95% CI, 1.56-18.93), being married (AOR = 2.5; 95% CI, 1.15-5.44), an HIV-positive status (AOR = 5.0; 95% CI, 1.41-20.3), and Pap smear as the initial screening modality (AOR = 4.9; 95% CI, 1.04-23.15).

Conclusion: Nearly half of the women treated for precancerous cervical lesions experienced persistent disease within 1 year, particularly those who were older, married, HIV-positive, or initially screened by Pap smear. These findings raise concerns about the effectiveness of current treatment and screening strategies.

Background: The incidence of central nervous system (CNS) leukemia is approximately 5%-10% in pediatric T-cell acute lymphoblastic leukemia (T-ALL), typically conferring a poor prognosis.

Materials and methods: We further investigated the relationship between prognosis and CNS status at different treatment stages, retrospectively examining 185 patients with pediatric T-ALL of 2131 consecutive patients with ALL seen between April 2008 and October 2020.

Results: Patients with CNS involvement-positive (CNSI+) disease during induction had lower initial platelet counts (P = .021), a higher proportion of ETP-ALL (P = .031), hepatomegaly (P = .034), and splenomegaly (P = .030), but a lower recurrence rate (P = .004) than those of patients with CNSI+ disease occurring in the consolidation/maintenance stages. Children with CNSI+ disease in the consolidation/maintenance stages by univariate/multivariate analyses had a significantly lower 10-year overall survival (OS) (46.2 ± 10.8%, 67.5 ± 9.5%, and 80.7 ± 3.4%, P = .003), event-free survival (EFS; 20.8 ± 8.3%, 48.0 ± 10.0%, and 77.4 ± 3.6%, P < .001), and a significantly higher cumulative recurrence rate (CRR) (76.8 ± 9.1%, 48.6 ± 10.1%, and 17.3 ± 3.3%, P < .001) than those of patients with CNSI+ disease in induction and those who were CNSI- (P values all <.05). PHF6, RELN, TP53, and IKZF1 mutations were more common in patients with CNSI+ observed during the consolidation/maintenance stages (P values all <.05), which may indicate a role in pathogenesis.

Conclusion: CNSI+ disease, especially in the consolidation/maintenance stage, was an independent poor prognostic factor in pediatric T-ALL. HSCT partially improved outcomes of children with T-ALL. Individualized treatment strategies containing a combination of immunotherapy and targeted therapy in addition to chemotherapy may improve patient outcomes.

Background: Ramucirumab plus paclitaxel after progression on fluoropyrimidine/platinum in metastatic gastric (GA) and gastroesophageal junction adenocarcinoma (GEJC) has shown improvement in overall survival over paclitaxel alone. However, the incidence of neuropathy was 46%. Therefore, there is an unmet need for novel treatment to minimize the long-term toxicity of neuropathy. We conducted a single arm phase II study of ramucirumab and trifluridine/tipiracil (FTD/TPI) in metastatic GA/GEJC.

Methods: Patients received ramucirumab at 8 mg/kg intravenously on day 1 and 15, and FTD/TPI at 35 mg/m2 orally twice daily on days 1-5 and days 8-12 on every 28-days cycle. The primary endpoint was 6-months overall survival (OS) rate and secondary endpoints were progression free survival (PFS), objective response rate and safety.

Results: At data cut-off of August 15, 2021, 23 pts were enrolled. The median age was 62 years. Most common treatment-related toxicities were diarrhea (39%), fatigue (39%), hypertension (39%), and nausea (35%). Most common treatment related Grade 3 or 4 adverse events were neutropenia (17%) and anemia (13%). The median PFS and OS was 4.8 and 6.1 months, respectively. The 6-month OS rate was 57% (95% CI: 36.4%-79.8%). Of the 18 evaluable patients with at least one post-baseline imaging, 2 (11%) patients demonstrated objective partial response, and 15 (83%) had stable disease.

Conclusion: The combination of ramucirumab and FTD/TPI demonstrated well-manageable safety profile. Our study did not meet primary endpoint. Ongoing clinical trials will help us understand if ramucirumab plus FTD/TPI is noninferior to ramucirumab/paclitaxel. The trial was registered at www.clinicaltrials.gov (NCT03686488).

Introduction: Extended-interval (EI) dosing of pembrolizumab (400 mg IV every 6 weeks) was approved across all solid tumors based on pharmacokinetic modeling and exposure-response analyses. Although EI dosing is more convenient for patients, whether the higher dose and extended dosing interval impacts immune-related adverse events (irAE) and clinical outcomes in patients with breast cancer is unknown.

Methods: In this retrospective cohort study, patients with breast cancer treated with pembrolizumab between 2017 and 2024 were included. Safety (irAE) and clinical outcomes including event-free survival (EFS), progression-free survival (PFS) and overall survival (OS) were compared between patients who received only standard-interval (SI) dosing (200 mg IV every 3 weeks) pembrolizumab and those who received ≥ 1 cycle of EI dosing.

Results: Of the 355 patients included, 59 (17%) received ≥ 1 cycle of EI and 296 (83%) received ≥ 1 cycle of only SI. Of those who received ≥ 1 cycle of pembrolizumab EI, 27 (45.8%) started with 200 mg, 7 (11.9%) started with 400 mg, 9 (15.2%) received only 400 mg, and 16 (27.1%) switched between dosing schedules. The majority (71%) of patients had early-stage disease, and 92% had triple-negative breast cancer. In patients with early-stage disease, rates of any-grade irAE were similar (p = 0.3), while grade 3 or higher irAE was lower in EI dosing versus SI (4% vs. 20%; p = 0.01). EFS and OS were similar between the two dosing regimens (p = 0.8 and p = 0.5, respectively). In patients with metastatic disease, any-grade irAE (p = 0.5), grade 3 or higher irAE (p = 0.1), PFS (p = 0.8), and OS (p = 0.5) were similar between the dosing regimens.

Conclusion: In this real-world study in which patients were often switched to EI dosing after initial SI therapy, safety and efficacy of EI dosing were maintained in patients with breast cancer. As more patients are treated with EI dosing, this data provides new evidence that switching to EI dosing is safe and effective, while improving medication burden for patients.

Purpose: Axillary lymph node dissection (ALND) has traditionally been recommended for breast cancer patients with positive sentinel lymph nodes (SLNs). Although omitting ALND is now widely accepted for patients undergoing breast-conserving surgery (BCS) with limited sentinel lymph node biopsy (SLNB) involvement, based on trials such as Z0011, evidence for patients undergoing total mastectomy (TM) remains limited and conflicting. This meta-analysis aimed to evaluate whether ALND can be safely omitted in TM patients with 1-2 positive SLNs by comparing survival outcomes between ALND and SLNB alone groups.

Methods: A systematic search of PubMed, Embase, Cochrane Library, and Web of Science (up to December 2024) identified 29 studies (6 randomized controlled trials and 23 observational) involving a total of 146 407 patients. Survival outcomes, including overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS), were pooled using random- or fixed-effects models. Heterogeneity and publication bias were assessed using I2 statistic, Begg's test, and Egger's test. Subgroup analyses were performed based on study design, type of surgical (TM vs. BCS), and pathological T-stage.

Results: Overall, no significant differences in OS (OR = 0.93, 95% confidence interval [CI]: 0.83-1.04), DFS (OR = 1.02, 95% CI: 0.87-1.20), or RFS (OR = 1.08, 95% CI: 0.89-1.30) were observed between ALND and SLNB alone groups. However, in the TM subgroup, ALND was associate with improved OS (OR = 0.75, 95% CI: 0.62-0.90). Similarly, patients with T3-4 tumors demonstrate better OS outcomes with ALND. No significant differences in DFS or RFS were observed across subgroups.

Conclusion: SLNB alone provides comparable survival outcomes to ALND in early breast cancer (EBC) patients with 1-2 positive SLNs, supporting its safety in those undergoing BCS. However, while our analysis suggests a potential survival advantage with ALND in TM patients and those with advanced T-stage (T3-4), this observation requires cautious interpretation due to potential selection bias, residual confounding from unmeasured variables and confounding by indication where ALND may reflect more intensive multimodal therapy rather than causally improving OS. Therefore, these subgroup findings should not be considered practice-changing at this stage. Further high-quality prospective studies are warranted to validate these associations and optimize patient selection criteria.