Oncologist [JOURNAL]
Sun
200 papers
The Impact of Relative Dose Intensity on pCR in Neoadjuvant Chemotherapy of Muscle-Invasive Urothelial Cancer: a Multicentre Retrospective Study.
Neola G, Flauto F, Caso C … +23 more , Montuori G, Maruzzo M, Lai E, Banna GL, Maffezzoli M, Rizzo M, Massari F, Mollica V, Scagliarini S, Conteduca V, Giannatempo P, Rametta A, Maiorano BA, Facchini G, Lenci E, Tambaro R, Grillone F, Bosso D, Crocetto F, Imbimbo C, Servetto A, Bianco R, Formisano L
Oncologist · 2026 Jul · PMID 42398048 · Publisher ↗
Cisplatin-based neoadjuvant chemotherapy (NAC) improves survival in muscle-invasive urothelial cancer (MIUC), yet pathological complete response (pCR) is achieved in a minority of patients. Relative dose intensity (RDI)...
Cisplatin-based neoadjuvant chemotherapy (NAC) improves survival in muscle-invasive urothelial cancer (MIUC), yet pathological complete response (pCR) is achieved in a minority of patients. Relative dose intensity (RDI) is a potentially modifiable determinant of chemotherapy efficacy, but its impact during NAC in MIUC remains unexplored. This multicentre retrospective study included patients with MIUC treated with cisplatin-gemcitabine NAC followed by radical cystectomy. RDI was calculated from original administration records and categorised as ≥ 85% versus <85%. The primary endpoint was pCR (ypT0N0M0). Secondary endpoints included overall survival (OS) and event-free survival (EFS). A total of 330 patients were included; 66% maintained RDI≥85%. Overall pCR rate was 25.2%. Patients with RDI≥85% achieved higher pCR rates compared with those with RDI<85% (29.7% vs 16.2%; p = 0.008). RDI≥85% remained independently associated with pCR in multivariable analysis (OR = 2.10; p = 0.032). Preserved RDI was also associated with improved EFS (HR = 0.65; p = 0.039) and OS (HR = 0.53; p = 0.026) at univariate analysis. Achievement of pCR was strongly associated with superior EFS (HR = 0.23; p < 0.001) and OS (HR = 0.35; p = 0.009). Preservation of cisplatin RDI≥85% during NAC is independently correlated with higher pCR rates and associated to a better survival trend in MIUC. Optimisation of chemotherapy delivery represents a clinically actionable strategy to enhance neoadjuvant efficacy.
Prevalence, treatment and survival of Malignant Peripheral Nerve Sheath Tumor in the Danish neurofibromatosis type 1 population.
Aggerholm-Pedersen N, Handrup MM, Thomassen SB … +7 more , Engelmann B, Kongstad KM, Jakobsen MV, Baad-Hansen T, Farholt S, Thomas D, Ejerskov C
Oncologist · 2026 Jul · PMID 42397226 · Publisher ↗
PURPOSE: While neurofibromatosis type 1 (NF1)-associated malignant peripheral nerve sheath tumor (nfMPNST) is often considered to have a particularly poor prognosis compared to sporadic malignant peripheral nerve sheath...
PURPOSE: While neurofibromatosis type 1 (NF1)-associated malignant peripheral nerve sheath tumor (nfMPNST) is often considered to have a particularly poor prognosis compared to sporadic malignant peripheral nerve sheath tumor (sMPNST), this assumption remains insufficiently substantiated. This study aimed to compare clinical characteristics, treatment outcome, and survival between nfMPNST and sMPNST in a nationwide Danish cohort. PATIENT AND METHOD: We conducted a retrospective cohort study of patients with malignant peripheral nerve sheath tumor (MPNST) in Denmark from 2000 to 2020. NF1-associated cases were identified through a national NF1 registry, while sporadic cases of MPNST were extracted from the Danish Sarcoma Database. Clinical, pathological, and treatment data were supplemented by chart review and national pathology records. Survival outcomes were analysed using Kaplan-Meier estimates and Cox proportional hazards models. RESULTS: A total of 146 patients were included of which 42 had nfMPNST and 104 sMPNST. Patients with nfMPNST were significantly younger at diagnosis (median 37 (min-max: 12-73) vs. 58 (min-max: 5-93) years, p < 0.001) and had larger tumors (>5 cm in 88% vs. 50%, p < 0.001). Wide margin resection was achieved less often in nfMPNST (35% vs. 66%, P = 0.003), and adjuvant radiotherapy was more commonly administered (61% vs. 36%). Five-year overall survival for localized disease was significantly lower in nfMPNST (44% vs. 63%, P = 0.03), with higher recurrence rates (69% vs. 49%, P = 0.049) and shorter time to recurrence (median 2.2 vs 3.4 years) Among 27 sMPNST tumors analysed by next-generations sequencing, 5 (19%) harbored pathogenic NF1 variants. CONCLUSION: nfMPNST presents at a younger age with more aggressive features and worse outcomes compared to sporadic cases. These findings support the need for tailored surveillance and treatment strategies in NF1 patients and highlight the potential role of NF1 alterations in sMPNST pathogenesis.
Molecular Tumor Board-Guided Osimertinib Therapy in EGFR L858R/Q701L-Mutant Lung Adenocarcinoma Supported by Functional Validation.
Albers-Leischner C, Ritgen M, Paulsen FO … +8 more , Schmidt B, von Bubnoff N, Gorantla SP, Letsch A, Janning M, Loges S, Bokemeyer C, Christopeit M
Oncologist · 2026 Jul · PMID 42391607 · Publisher ↗
BACKGROUND: Rare or compound EGFR variants in non-small cell lung cancer (NSCLC) can create substantial therapeutic uncertainty, particularly when accompanied by additional co-alterations with potential resistance implic...
BACKGROUND: Rare or compound EGFR variants in non-small cell lung cancer (NSCLC) can create substantial therapeutic uncertainty, particularly when accompanied by additional co-alterations with potential resistance implications. In such settings, molecular tumor boards (MTBs) may integrate genomic, functional, and clinical data to guide treatment selection. CASE PRESENTATION: A 59-year-old Caucasian woman was diagnosed with metastatic lung adenocarcinoma involving the lungs, bones, and lymph nodes. Histopathology showed a TTF-1 positive pulmonary adenocarcinoma with low PD-L1 espression. MOLECULAR FINDINGS: Next-generation sequencing identified a compound EGFR alteration consisting of L858R and Q701L, along with additional alterations in PIK3CA, ATM, and CTNNB1 and loss of CDKN2A/B, MLH1 and BAP1. FUNCTIONAL AND MOLECULAR TUMOR BOARD ASSESSMENT: To resolve this uncertainty, the EGFR mutations were recreated in vitro and characterized within national Network Genomic Medicine (nNGM) preclinical platform. In Ba/F3 models, the EGFR L858R/Q701L co-mutation showed sensitivity to first-, second-, and third-generation EGFR tyrosine kinase inhibitors. After integrating the molecular profile, functional data, and clinical context, the institutional MTB recommended in-label therapy with Osimertinib. OUTCOME: Treatment resulted in rapid clinical improvement and a radiologically confirmed partial remission followed by durable disease control for 18 months. Disease progression occurred thereafter, and the patient died 23.4 months after initial diagnosis. CONCLUSION: This case highlights the importance of functional validation and multidisciplinary tumor board discussion in interpreting complex genomic profiles and guiding personalized therapy in NSCLC.
Phase 2 Dose Expansion Trial of OBI-3424, a DNA-Alkylating Prodrug, in Patients with Advanced Solid Tumors Expressing AKR1C3.
Tsimberidou AM, Verschraegen C, Sigal D … +7 more , Lenz HJ, Hochster H, Baysal MA, Chakraborty A, Lee I, Ristoski K, Xu D
Oncologist · 2026 Jul · PMID 42390142 · Publisher ↗
BACKGROUND: OBI-3424 is an investigational small molecule prodrug. In a dose-escalation trial, the OBI-3424 recommended phase 2 dose (RP2D) was 12 mg/m2 administered every 21 days. In this phase 2 dose-expansion trial, w...
BACKGROUND: OBI-3424 is an investigational small molecule prodrug. In a dose-escalation trial, the OBI-3424 recommended phase 2 dose (RP2D) was 12 mg/m2 administered every 21 days. In this phase 2 dose-expansion trial, we evaluated the safety and efficacy of OBI-3424 in pancreatic adenocarcinoma and other solid tumor types ("basket" cohort). METHODS: Patients with advanced solid tumors and AKR1C3 IHC H-score of ≥ 100 were treated at the RP2D of OBI-3424. Tumor response, progression-free survival (PFS), overall survival (OS), and treatment-emergent adverse events (TEAEs) were assessed (www.clinicaltrials.gov NCT03592264). RESULTS: Of the 29 patients treated, 26 were evaluable for response (pancreatic adenocarcinoma, n = 10; basket cohort, n = 16). In the pancreatic adenocarcinoma cohort, stable disease (SD) was observed in 40.0% of patients and the median PFS and OS durations were 1.35 months and 3.8 months, respectively. In the basket cohort, the objective response rate was 6.3% (1 of 16 patients had a partial response), 50% of patients had SD and the median PFS and OS durations were 2.53 months and 5.32 months, respectively. The most common TEAEs in both cohorts were anemia, fatigue, and thrombocytopenia. CONCLUSION: While OBI-3424 demonstrated a favorable safety profile, limited efficacy led to early trial termination.
Divergent Biology and Outcomes of Somatic Transformations in Germ Cell Tumors.
Thomas Z, Johns AC, Glover M … +13 more , Crupi E, Nieto YL, Ward JF, Karam JA, Hofstetter WL, Desai M, Choi SL, Shah AY, Lin J, Moussa MJ, Jiang CY, Alhalabi O, Campbell MT
Oncologist · 2026 Jun · PMID 42378441 · Publisher ↗
PURPOSE: Somatic-type malignancy (SM) of germ cell tumor (GCT) is rare but demonstrates aggressive behavior. Differences by primary site, time to transformation, and mutational status remains poorly characterized. PATIEN...
PURPOSE: Somatic-type malignancy (SM) of germ cell tumor (GCT) is rare but demonstrates aggressive behavior. Differences by primary site, time to transformation, and mutational status remains poorly characterized. PATIENTS AND METHODS: We reviewed all SM patients from June 2016 - May 2025 at a tertiary referral center. Time to somatic transformation (TST) was defined from initial GCT diagnosis to SM detection. SM were classified based on time of detection- at initial diagnosis (de novo), at consolidative surgery, relapse under 5 years, and evolved SM- relapse after 5 years. Descriptive statistics, Kaplan-Meier estimates, and Cox regression analyses were used. RESULTS: 72 patients were identified: 40 (56%) with testicular, 24 (33%) with mediastinal, and 8 (11%) with other primaries. 22/24 (92%) mediastinal tumors with SM had sarcomatous transformation. Sarcoma was seen in 25/42 (60%) of de novo SM while adenocarcinoma was detected as an evolved entity in 5/6 (83.3%) cases. Embryonic type neuroectodermal tumor (ENET) histology carried poor prognosis compared to non-ENET histology (median OS 1.8 vs 8 years; HR 1.94, p = 0.1). Genomic data available showed PTEN-AKT-mTOR pathway mutations (33%) and TP53 mutations (33%), enriched in extra-gonadal sarcomatous SM. CONCLUSIONS: SM exhibits temporal, histologic, and molecular distinctions across primary sites. Response to front-line therapy and survival outcomes are poor. Future direction includes the exploration of underlying predictors of transformation and identification of targetable alterations in the relapsed setting.
Modernizing Disease Assessment in Prostate Cancer Trials: The Prostate Cancer Working Group 4 Framework.
Zugman M, Barata PC
Oncologist · 2026 Jun · PMID 42371793 · Publisher ↗
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Use of liposomal irinotecan with 5-FU and oxaliplatin (NALIRIFOX) in neoadjuvant pancreatic adenocarcinoma: NEO-Nal-IRI trial.
George TJ, Lin T, Nassour I … +15 more , Rogers SC, Jang T, Sahin I, Ramnaraign BH, Fabregas J, Hitchcock K, Liu G, Russell KB, Turk AA, Kayaleh O, Fan ZH, DeRemer DL, Thomas RM, Lee JH, Hughes SJ
Oncologist · 2026 Jun · PMID 42371783 · Publisher ↗
BACKGROUND: While neoadjuvant FOLFIRINOX is an effective regimen for pancreatic ductal adenocarcinoma (PDAC), toxicity frequently limits its use. Nanoliposomal irinotecan (nal-IRI) offers improved pharmacokinetic propert...
BACKGROUND: While neoadjuvant FOLFIRINOX is an effective regimen for pancreatic ductal adenocarcinoma (PDAC), toxicity frequently limits its use. Nanoliposomal irinotecan (nal-IRI) offers improved pharmacokinetic properties and may mitigate some of the side effects. We conducted a multi-institutional, phase II study to evaluate the safety and clinical activity of neoadjuvant NALIRIFOX (nal-IRI, 5-fluorouracil, leucovorin, and oxaliplatin) in patients with resectable and borderline resectable (R/BR) PDAC. METHODS: Patients with untreated R/BR PDAC received eight cycles of neoadjuvant NALIRIFOX. The primary endpoint was the 30-day post-operative major complication rate among resected patients. Secondary endpoints included treatment completion rate, R0 resection rate, objective response rate (ORR), biochemical (CA19-9) and radiographic responses, nodal downstaging, and quality of life (QoL by FACT-G). RESULTS: Of the 45 enrolled patients, 73% completed all eight cycles of neoadjuvant NALIRIFOX. 34 patients (76%) underwent attempted surgery, of whom 29 (64%) had complete resection (15 BR patients and 14 R patients). The 30-day post-operative major complication rate was 10% (95% CI, 2.2-27%, p = 0.012), meeting the pre-specified threshold. R0 resection was achieved in 90% of resected patients. The radiographic ORR was 45% (95% CI, 29-62%), and the clinical benefit rate was 73% (95% CI, 58-85%). CONCLUSION: Neoadjuvant NALIRIFOX is a safe and active regimen in R/BR PDAC with a low post-operative complication rate, high treatment completion and R0 resection rates, and meaningful clinical responses. These findings support further investigation of NALIRIFOX as part of a total neoadjuvant therapy (TNT) approach in PDAC. [ClinicalTrials.gov identifier: NCT03483038].
Dose-Expansion Study of OBI-999, a Globo H-Targeting Antibody-Drug Conjugate, in Patients with Advanced Solid Tumors.
Tsimberidou AM, Sigal D, Varghese A … +11 more , Vaena D, Bai LY, Chen MH, Yeh CN, Yen CJ, Baysal MA, Chakraborty A, Lee I, Shia CS, Ristoski K, Xu D
Oncologist · 2026 Jun · PMID 42371780 · Publisher ↗
BACKGROUND: OBI-999 is an antibody-drug conjugate consisting of the Globo H-targeting antibody OBI-888 linked to the cytotoxic payload monomethyl auristatin E. In a dose-escalation study, the OBI-999 recommended phase 2...
BACKGROUND: OBI-999 is an antibody-drug conjugate consisting of the Globo H-targeting antibody OBI-888 linked to the cytotoxic payload monomethyl auristatin E. In a dose-escalation study, the OBI-999 recommended phase 2 dose (RP2D) was 1.2 mg/kg every 3 weeks. This dose-expansion study evaluated the efficacy and safety of OBI-999 in patients with pancreatic cancer, colorectal cancer (CRC), or other tumor types ("basket cohort") and tumoral Globo-H H-scores ≥100 (NCT04084366). PATIENTS AND METHODS: Patients were treated at the RP2D of OBI-999. We assessed response, progression-free survival (PFS), treatment-emergent adverse events (TEAEs), and pharmacokinetics of OBI-999. RESULTS: Of 29 patients treated, 23 were evaluable for response. Eight (34.8%) had stable disease): pancreatic cancer, 4 of 7; CRC, 2 of 8; basket cohort, 2 of 8. No objective response was noted. The median time on treatment was 22 days. No association between H-score and tumor size reduction was noted. Median PFS was 3.3 months, 1.3 months, and 1.4 months in the pancreatic, CRC, and basket cohorts, respectively. One patient (3.4%) experienced a serious TEAE related to OBI-999 (febrile neutropenia) that led to discontinuation of OBI-999; the TEAE resolved 3 days after onset. OBI‑999 showed consistent pharmacokinetics with comparable exposure at the RP2D across cohorts. CONCLUSION: OBI-999 had a favorable safety profile. Although 34.8% of patients had disease stabilization, no objective response was noted, likely owing to inefficient antigen binding, suboptimal systemic exposure at the tolerated dose, and complex tumor biology.
Comparison of Allo-HSCT outcomes after CAR-T therapy versus chemotherapy in pediatric patients with relapsed/refractory B-ALL: a retrospective study.
Li B, Luo C, Lu J … +27 more , Cai J, Zhu Y, Li CK, Guo Y, Jiang H, Huang X, Cheng Y, Pan J, Sun Z, Feng X, Liu X, Chen K, Yu J, He G, Wang J, Liu A, Wu X, Wan L, Wang H, Xiao X, Qin M, Pan K, Lu J, Xiao P, Chen J, Sun R, Hu S
Oncologist · 2026 Jun · PMID 42371770 · Publisher ↗
BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a curable treatment for refractory/relapse B-cell acute lymphoblastic leukemia (R/R B-ALL).Traditional chemotherapy or Chimeric antigen receptor T-cell (CAR-T...
BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a curable treatment for refractory/relapse B-cell acute lymphoblastic leukemia (R/R B-ALL).Traditional chemotherapy or Chimeric antigen receptor T-cell (CAR-T) therapy are both important methods to achieve MRD negativity before HSCT. However, which treatment is preferred needs to be clarified. PATIENTS AND METHODS: In this study, 269. PATIENT: s with R/R B-ALL who underwent allo-HSCT after CAR-T cell therapy (CAR-T, n = 142) or chemotherapy (CT, n = 127) were enrolled from multicenters. RESULTS: The 3-year overall survival (OS) after transplantation was 66.8% in the CAR-T group and 72.3% in the chemotherapy (CT) group. The 3-year relapse-free survival (RFS) was 65.3% in the CAR-T group and 65.9% in the CT group. The 3-year graft-versus-host disease, relapse-free survival (GRFS) and cumulative incidence of relapse (CIR) were also similar between the two groups. Among patients who achieved first complete remission (CR1) before transplantation, the proportion receiving chemotherapy was significantly higher than that receiving CAR-T therapy (37.5% vs. 13.6%; P < 0.001). In this CR1 subgroup, the CT group demonstrated superior outcomes, including improved OS, RFS, and GRFS. CONCLUSION: In pediatric R/R B-ALL, CAR-T bridging to HSCT appears to yield post-transplant survival comparable to chemotherapy, though a higher rate of moderate to severe chronic GVHD was observed. CAR-T may be a reasonable option, but closer GVHD monitoring seems warranted.
Patient, care partner, and oncologist perspectives on clinically important survival thresholds after considering time toxicity in advanced cancer.
Gupta A, Lin K, Jansen RJ … +8 more , Stevens SX, George M, Breininger A, Booth CM, Parsons HM, Ziegenfuss JY, Vogel RI, Blaes AH
Oncologist · 2026 Jun · PMID 42366681 · Full text
A treatment's time toxicity (measured using contact days) can decrease days spent at home (home days). We evaluated the minimum clinically important difference (MCID) and non-inferiority margin (NIM) of home days, and tr...
A treatment's time toxicity (measured using contact days) can decrease days spent at home (home days). We evaluated the minimum clinically important difference (MCID) and non-inferiority margin (NIM) of home days, and treatment acceptance when all additional survival time was spent in health care by surveying people with lived (patients, n = 42; informal care partners, n = 29) and professional (oncologists, n = 8) experience of advanced cancer. All 3 groups reported similar MCIDs and NIMs (6-month survival; median MCID range, 14-15; P = .79; median NIM range, 5-11; P = .14). Care partners (48%) and patients (21%) more often accepted 2-week survival gains without an increase in home days than oncologists (0%), P = .09. Caregivers reported altruism guided their responses, and clinicians' responses in stated-preference work may differ from revealed-preferences in the clinic. By empirically deriving MCID/NIM for home days and evaluating treatment acceptance, this work will aid trial design and decision studies using an endpoint of home days.
Biomarker testing patterns among patients newly diagnosed with metastatic non-small cell lung cancer, prostate cancer, and bladder cancer.
Mahmud S, Dwyer Orr L, Cline M … +5 more , Mirsalehi A, Lisi M, Ensley L, Brisbin L, Paulson RS
Oncologist · 2026 Jun · PMID 42366674 · Publisher ↗
BACKGROUND: National clinical guidelines recommend biomarker testing to identify actionable alterations across cancers, supporting personalized treatment. METHODS: This retrospective database study characterized biomarke...
BACKGROUND: National clinical guidelines recommend biomarker testing to identify actionable alterations across cancers, supporting personalized treatment. METHODS: This retrospective database study characterized biomarker testing patterns among adult patients newly diagnosed with metastatic non-small cell lung cancer (NSCLC), prostate cancer, or bladder cancer (January 2018-December 2022), receiving care within a large regional community oncology network in the West South-Central United States. RESULTS: Of 18 491 patients with NSCLC, 20 810 with prostate cancer, and 4120 with bladder cancer, 7383 (40%), 4985 (24%), and 888 (22%), respectively, had metastatic disease. For these metastatic subgroups, biomarker testing rates were 80% (NSCLC), 34% (prostate), and 42% (bladder). Median time from disease diagnosis to first test order was 10 days (NSCLC), 98 days (prostate), and 23 days (bladder), with differences observed across racial and ethnic groups. Among tested patients, actionable mutations were identified in 29% (NSCLC), 25% (prostate), and 14% (bladder) of patients, and targeted therapy was received by 54%, 15%, and 38% of these patients, respectively. Among patients who initiated treatment prior to receipt of test results, 72% (NSCLC), 12% (prostate), and 30% (bladder) subsequently switched to targeted therapy following a positive result. Testing rates increased between 2018 and 2022 for all cohorts; result turnaround times improved in prostate and bladder cancers. CONCLUSIONS: Biomarker testing was highest in metastatic NSCLC and lower in prostate and bladder cancer in this community oncology setting. Despite improvements over time, gaps remain in timely testing and use of targeted therapies, highlighting opportunities to optimize precision oncology implementation.
Phase IB/II study of alpelisib combined with paclitaxel in patients with PIK3CA-altered metastatic or recurrent gastric cancer.
Kim JW, Yoon S, Ryu MH … +9 more , Lim SH, Kim ST, Kim TY, Han HS, Jung M, Kim JW, Kim JH, Zang DY, Lee KW
Oncologist · 2026 Jun · PMID 42363423 · Publisher ↗
BACKGROUND: This phase IB/II study assessed safety, pharmacokinetics, and efficacy of alpelisib, a selective PI3Kα inhibitor, plus weekly paclitaxel in patients with PIK3CA-altered metastatic or recurrent gastric cancer...
BACKGROUND: This phase IB/II study assessed safety, pharmacokinetics, and efficacy of alpelisib, a selective PI3Kα inhibitor, plus weekly paclitaxel in patients with PIK3CA-altered metastatic or recurrent gastric cancer (GC). METHODS: In phase IB, patients with advanced solid tumors received alpelisib 250 mg (dose level [DL] 0) or 300 mg (DL1) once daily plus paclitaxel 70 mg/m2 on days 1, 8, and 15 every 4 weeks to determine maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and the recommended phase II dose (RP2D). In phase II, patients with PIK3CA-altered GC received RP2D, and the primary endpoint was 4-month progression-free survival (PFS). Subjects with diabetes or those with risk factors for diabetes who also had impaired glucose tolerance were excluded. Pharmacokinetic sampling was performed in phase IB at cycle 1, days 1 (initial dose) and 8 (steady state). RESULTS: In phase IB, MTD was not reached; RP2D was established at DL1. Two patients developed DLTs at DL0 (grade 3 hyperglycemia, diarrhea, and fatigue) and DL1 (grade 3 hyponatremia). Toxicities were consistent with known PI3Kα inhibitor plus taxane combination profiles and were generally manageable. In phase II (n = 9), the 4-month PFS rate was 22.2%, and enrollment was discontinued early for futility; no objective responses were observed, and the median PFS was 2.6 months. Alpelisib exposure, assessed by Cmax and AUC0-24, was within expected ranges, and prior gastrectomy was associated with lower exposure. CONCLUSION: Alpelisib plus paclitaxel was tolerable and pharmacologically feasible with a defined RP2D but showed limited efficacy in PIK3CA-altered GC.
Very Young Age Stratification and Development of a Multiple-Imputation Cox Nomogram for Disease-Free Survival in Breast Cancer Women Aged ≤40 Years.
Lyu X, Zhong Y, Zhou Y … +5 more , Sun Q, Mao F, Shen S, Lin Y, Huang X
Oncologist · 2026 Jun · PMID 42363420 · Publisher ↗
BACKGROUND: Breast cancer in women aged 40 years or younger is clinically heterogeneous, yet risk stratification within this already-young population and rigorously validated disease-free survival (DFS) tools remain limi...
BACKGROUND: Breast cancer in women aged 40 years or younger is clinically heterogeneous, yet risk stratification within this already-young population and rigorously validated disease-free survival (DFS) tools remain limited. METHODS: We retrospectively analyzed 2,069 women aged 40 years or younger who underwent surgery between 2006 and 2021. Patients were compared as younger than 35 versus 35-40 years to assess the prognostic relevance of very young age. Age was additionally modeled continuously using restricted cubic splines, and the optimal cutpoint was examined using maximally selected rank statistics. DFS was evaluated with Kaplan-Meier estimates and multivariable Cox models. We developed a Cox nomogram for 3- and 5-year DFS using age, molecular subtype, pathologic T stage, pathologic N stage, histologic grade, Ki-67 category, and calendar period. Missing covariates were handled by multiple imputation by chained equations (20 imputations), with internal validation by 1,000 bootstrap resamples and temporal validation of a reduced model. RESULTS: Of 2,069 women, 779 were younger than 35 years. Very young patients had more aggressive features, including higher frequencies of HER2-positive and triple-negative disease, grade 3 tumors, high Ki-67, and advanced T/N stage. Overall 5-year DFS was 88.9%; patients younger than 35 years had worse 5-year DFS (85.0% vs 91.4%; log-rank P = 0.0005; absolute difference 6.4 percentage points). Spline modeling showed a continuous, monotonic increase in risk with younger age without evidence of non-linearity (P = 0.88), and maximally selected rank statistics identified 35 years as the optimal cutpoint (standardized log-rank z = 3.51, P < 0.001). After adjustment for molecular subtype and pathologic T and N stage, age younger than 35 years remained independently associated with worse DFS (hazard ratio 1.34, 95% CI 1.03-1.76; P = 0.032). The multiple-imputation nomogram had an apparent C-index of 0.660, a bootstrap-corrected C-index of 0.636, and a temporal-validation C-index of 0.617. CONCLUSION: Very young age identifies a higher-risk subgroup among women aged 40 years or younger with breast cancer. A multiple-imputation Cox nomogram based on routinely available variables provided moderate discrimination and acceptable calibration and is best suited to broad risk-group stratification rather than precise individual-level prediction.
Targeted Therapy in Recurrent Clival Chordoma: A Case Report of Response to Ivosidenib.
Rahbarlayegh E, Kesari S
Oncologist · 2026 Jun · PMID 42348221 · Publisher ↗
Genetic and molecular alterations in cancer cells can serve as therapeutic targets and enable more precise, individualized treatment strategies. In rare tumors with limited systemic treatment options, molecular profiling...
Genetic and molecular alterations in cancer cells can serve as therapeutic targets and enable more precise, individualized treatment strategies. In rare tumors with limited systemic treatment options, molecular profiling may help identify therapeutic opportunities when conventional approaches are exhausted. We report the case of a 72-year-old woman with a long-standing, multiply recurrent clival chordoma and no remaining surgical or radiation options who experienced a meaningful clinical and metabolic response to targeted therapy. Comprehensive tumor molecular profiling identified an activating isocitrate dehydrogenase 1 (IDH1) p. R132C mutation, which guided off-label treatment with the IDH1 inhibitor ivosidenib. Treatment was well tolerated and associated with durable radiographic response with tumor reduction, partial metabolic response on FDG-PET imaging, and clinically significant improvement in neurological symptoms and quality of life. This case highlights the value of molecular tumor board-guided interpretation of genomic alterations and illustrates the potential role of IDH-targeted therapy in select patients with recurrent chordoma.
Beyond the Binary: A Nationwide Study of Physician Decision Orientations Toward Artificial Hydration in Terminal Cancer Care.
Wu CY, Yang JH, Shih CY … +7 more , Hsiao IA, Huang HL, Peng JK, Tang CC, Yao CA, Tsai JS, Cheng SY
Oncologist · 2026 Jun · PMID 42332810 · Publisher ↗
BACKGROUND: Artificial hydration (AH) in terminally ill cancer patients remains ethically and clinically controversial. Although evidence suggests limited benefit near the end of life, AH is frequently administered, part...
BACKGROUND: Artificial hydration (AH) in terminally ill cancer patients remains ethically and clinically controversial. Although evidence suggests limited benefit near the end of life, AH is frequently administered, particularly in East Asian settings where it may carry symbolic meaning. This study conceptualized physician decision-making as a clinical spectrum and examined demographic, clinical, and ethical factors associated with AH decision orientations. MATERIALS AND METHODS: A nationwide cross-sectional survey of palliative care-trained physicians in Taiwan assessed clinical practices and ethical domains (autonomy, beneficence, non-maleficence, justice, cultural, and emotional factors). Scenario-based scores were used to derive continuation, withdrawal, and variability indices. Two-step cluster analysis identified decision-orientation profiles. Group differences were analyzed using ANOVA, chi-square tests, and multinomial logistic regression. RESULTS: Among 377 respondents, four decision-orientation clusters emerged: contextual/proportional, selective continuation, conservative/continuation-leaning balancing, and consistent withdrawal. Several demographic and professional characteristics differed across clusters. Ethical domains also differed significantly. Multinomial regression showed that cultural and emotional factors were associated with contextual/proportional orientation, whereas beneficence independently predicted selective continuation orientation. Hydration volume and consideration of life expectancy differed across clusters, supporting behavioral distinctions among decision orientations. CONCLUSION: AH decision-making reflects multiple context-sensitive physician orientations shaped by both ethical considerations and professional characteristics, rather than a binary continuation-withdrawal model.
Genomic determinants and an exploratory prognostic model for immunotherapy outcomes in recurrent or metastatic cervical cancer.
Gu L, Zhu B, Liu C … +6 more , Wu X, Zhang Y, Yin J, Wang F, Hu T, Wu Y
Oncologist · 2026 Jun · PMID 42332782 · Full text
BACKGROUND: Immune checkpoint inhibitors (ICIs) improve outcomes in recurrent or metastatic cervical cancer, but responses are heterogeneous and biomarkers beyond programmed death-ligand 1 (PD-L1) are limited. MATERIALS...
BACKGROUND: Immune checkpoint inhibitors (ICIs) improve outcomes in recurrent or metastatic cervical cancer, but responses are heterogeneous and biomarkers beyond programmed death-ligand 1 (PD-L1) are limited. MATERIALS AND METHODS: Targeted sequencing of 437 cancer-related genes was performed in 42 patients receiving ICI-based therapy. Genomic correlates of progression-free survival (PFS) were evaluated, and an exploratory prognostic model was developed using least absolute shrinkage and selection operator regression and multivariable Cox regression. The Cancer Genome Atlas (TCGA) cohort was used for transcriptomic analysis. RESULTS: The cohort included 42 patients, with a median age of 51 years; 85.7% were human papillomavirus-positive, 90.5% had squamous cell carcinoma, and 54.8% had a programmed death-ligand 1 combined positive score (PD-L1 CPS) ≥5. Frequent alterations included PIK3CA (57.1%), FBXW7 (21.4%), TERT (21.4%), BAP1 (19.0%), and EP300 (16.7%). Tumor mutational burden-associated mutations in PIK3CA, EP300, CREBBP, and TERT were associated with prolonged PFS (P < .001), whereas PD-L1-associated mutations showed numerically longer PFS (P = .170). EP300 (P = .007), PIK3CA (P < .01), and homologous recombination repair pathway alterations (P = .016) were associated with favorable PFS, whereas KEAP1 (P < .01) and TP53 (P = .010) mutations were associated with shorter PFS. A five-feature genomic model stratified patients into high- and low-risk groups (P < .001, 1-year AUC = .889). In the exploratory cohort, high-risk patients showed numerically shorter PFS (P = .060). In TCGA samples, high-risk tumors showed enrichment of angiogenesis, epithelial-mesenchymal transition, hypoxia, inflammatory response, and tumor necrosis factor-α/nuclear factor-κB signaling. CONCLUSION: Specific genomic alterations may help stratify immunotherapy outcomes in recurrent or metastatic cervical cancer. The proposed genomic risk model remains exploratory and requires validation in larger, independent cervical cancer cohorts.
Follow-up rescreening among women living with human immunodeficiency virus who tested positive and treated for cervical pre-cancer lesions in South Ethiopia.
Lencha B, Geda B, Ahmed K … +2 more , Kapps L, Spigt M
Oncologist · 2026 Jun · PMID 42316805 · Full text
BACKGROUND: Women living with human immunodeficiency virus face a heightened risk of cervical cancer. Lack of follow-up rescreening among women with cervical lesions could result in increased risk of cancer-related morbi...
BACKGROUND: Women living with human immunodeficiency virus face a heightened risk of cervical cancer. Lack of follow-up rescreening among women with cervical lesions could result in increased risk of cancer-related morbidity and mortality. METHODS: A retrospective cross-sectional study was conducted among 191 women living with HIV who tested positive for visual inspection with acetic acid and were treated from September 2020 to September 2023. A data extraction checklist was used to collect data from October 1, 2023 to March 30, 2024. Descriptive statistics was computed and then logistic regression analysis was used to assess the association between the independent variables and follow-up rescreening. The association was ascertained using adjusted odds ratio (AOR) and 95% confidence interval (CI). Statistical significance was declared at a P-value less than 0.05. RESULT: The mean age of the participants was 36.88 (±7.29) years. Slightly less than one-third (60, 31.4%) of the women came back for follow-up rescreening within 3 years. Those women who were educated [AOR = 2.2, 95% CI: 1.03-4.68] and treated by Cryotherapy [AOR = 2.4, 95% CI: 1.1-5.4] were more likely to come back for rescreening compared to those who were uneducated and treated by thermal ablation, respectively. CONCLUSION: Follow-up rescreening for cervical pre-cancer remains low. Women's educational status and treatment modality affect the follow-up rescreening. Proper counselling on post-treatment follow-up and available screening and treatment options is very crucial to improve adherence to protocol. A qualitative study is warranted to identify the challenges of follow-up rescreening.
Robust response to pembrolizumab in temozolomide-associated hypermutated and microsatellite instability-high functional pancreatic neuroendocrine tumor.
Grewal US, Shi CW, Muzahir S … +3 more , Ear PH, Concors SJ, Halperin DM
Oncologist · 2026 Jun · PMID 42296390 · Full text
Pancreatic neuroendocrine tumors (PanNETs) are typically characterized by low tumor mutational burden and limited responsiveness to immune checkpoint inhibitors. Emerging evidence suggests that prior exposure to alkylati...
Pancreatic neuroendocrine tumors (PanNETs) are typically characterized by low tumor mutational burden and limited responsiveness to immune checkpoint inhibitors. Emerging evidence suggests that prior exposure to alkylating chemotherapeutic agents may be associated with a hypermutated phenotype (along with DNA mismatch repair dysfunction or DNA damage response gene alterations), potentially sensitizing tumors to immunotherapy. We present a case of a 68-year-old woman with metastatic functional PanNET (VIPoma) who developed a treatment-associated hypermutated, microsatellite instability-high phenotype following capecitabine-temozolomide therapy. Treatment with pembrolizumab resulted in a robust clinical, biochemical, and radiographic response. This case highlights dynamic genomic evolution in PanNETs and underscores the importance of serial molecular profiling in guiding therapeutic decisions.
Can clinicians predict individual patient outcomes in neuroendocrine tumors treated with [177Lu]Lu-DOTATATE?
López-Robles J, Mitjavila M, Jimenez-Fonseca P … +21 more , Marín-Melero I, Belló P, Pubul V, Garcia-Burillo A, Hernando J, Llana B, Ardila J, Arbizu J, Valverde R, Velasco M, Castellón M, Alonso-Gordoa T, García-Cañamaque L, Cano JM, Tabuenca MJ, Riesco MC, Custodio AB, Piñeiro A, Balaguer-Muñoz D, Nevares M, Carmona-Bayonas A
Oncologist · 2026 Jun · PMID 42296387 · Full text
BACKGROUND: Peptide receptor radionuclide therapy (PRRT) has become a cornerstone in the management of neuroendocrine tumors (NETs), yet optimal sequencing and patient selection remain unsettled. This study aimed to deve...
BACKGROUND: Peptide receptor radionuclide therapy (PRRT) has become a cornerstone in the management of neuroendocrine tumors (NETs), yet optimal sequencing and patient selection remain unsettled. This study aimed to develop and internally validate the NEPTUNE score to predict progression-free survival (PFS) in advanced NETs patients receiving [177Lu]Lu-DOTATATE. MATERIALS AND METHODS: Real-world data from the nationwide SEPTRALU registry and the Jules Bordet Institute included patients with advanced NETs treated with [177Lu]Lu-DOTATATE. Predictors of PFS were identified using an accelerated failure time model and combined into the NEPTUNE score. Internal validation was performed using bootstrap resampling. This tool was subsequently transformed into a nomogram and an interactive web-based calculator to enhance its integration into routine clinical practice. RESULTS: The cohort comprised 647 patients with diverse NET subtypes: pancreatic (39%), midgut (30%), bronchopulmonary (9%), pheochromocytoma/paraganglioma (3%), other gastroenteropancreatic (11%), and other non-gastroenteropancreatic (8%). The NEPTUNE score incorporates ten routinely available variables: ECOG performance status, PRRT line, Ki67 index, number of metastatic sites, primary tumor site, sex, Krenning grade, surgical resection of metastases, presence of liver metastases, and time from advanced tumor diagnosis to PRRT. The score demonstrated strong performance, with an Integrated Brier Score of 0.201 and a bias-corrected C-index of 0.702, indicating good calibration and discrimination. CONCLUSIONS: The NEPTUNE score is a promising tool for predicting individual PFS in patients with advanced NETs treated with [177Lu]Lu-DOTATATE. By integrating readily available clinical variables, it may support clinical decision-making. However, external validation is required before broader clinical implementation.
Lymphovascular and perineural invasion guides adjuvant therapy after neoadjuvant chemoimmunotherapy in esophageal squamous cell carcinoma.
Huang Y, Chen M, Yang Z … +7 more , Cai B, Zhang Y, Zhang S, Zeng T, Yu J, Chen C, Zheng B
Oncologist · 2026 Jun · PMID 42287715 · Full text
BACKGROUND: Lymphovascular (LVI) and perineural invasion (PNI) are adverse pathological features in esophageal squamous cell carcinoma (ESCC). We evaluated the prognostic significance of combined LVI/PNI (LNI) after neoa...
BACKGROUND: Lymphovascular (LVI) and perineural invasion (PNI) are adverse pathological features in esophageal squamous cell carcinoma (ESCC). We evaluated the prognostic significance of combined LVI/PNI (LNI) after neoadjuvant chemoimmunotherapy (nCIT) and the potential benefit of adjuvant therapy. METHODS: We retrospectively analyzed 473 ESCC patients undergoing nCIT followed by curative resection. LNI status was assessed in resected specimens. Survival outcomes were compared between LNI-positive and -negative patients using propensity score matching and multivariable Cox models. External validation was performed using an independent patient-level dataset. RESULTS: LNI was present in 21% of patients. LNI-positive patients had worse 3-year overall survival (OS) (49.8% vs 76.4%) and disease-free survival (DFS) (41.7% vs 69.3%), which remained significant after matching. LNI independently predicted inferior OS (hazard ratio [HR] 1.52, P = .022) and DFS (HR 1.40, P = .045). Recurrence occurred more frequently in LNI-positive patients (39.4% vs 19.8%, P < .001), predominantly locoregional. Among LNI-positive patients, adjuvant therapy improved 3-year OS (56.8% vs 32.4%) and DFS (49.7% vs 20.7%; adjusted HR 0.43, P = .002). External validation confirmed these findings, with independent prognostic impact of LNI and benefit from adjuvant therapy. CONCLUSIONS: LNI after nCIT is an independent adverse prognostic factor in ESCC. Patients with these high-risk pathological features have markedly worse outcomes but appear to derive significant benefit from adjuvant therapy, supporting its incorporation into postoperative management.
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