Oncologist [JOURNAL]
Sun
200 papers
Clinical and molecular response to vorasidenib in post-transplant patient with IDH2-mutant intrahepatic cholangiocarcinoma.
Altiery De Jesus VV, McMahon T, Young SE … +3 more , Zabransky DJ, Yarchoan M, Baretti M
Oncologist · 2026 Jun · PMID 42286810 · Full text
BACKGROUND: IDH2 mutations occur in a small subset of intrahepatic cholangiocarcinoma and currently lack approved targeted therapies. CASE PRESENTATION: We report a post-transplant patient with IDH2-mutant intrahepatic c...
BACKGROUND: IDH2 mutations occur in a small subset of intrahepatic cholangiocarcinoma and currently lack approved targeted therapies. CASE PRESENTATION: We report a post-transplant patient with IDH2-mutant intrahepatic cholangiocarcinoma who developed recurrent disease following multiple treatments for hepatocellular carcinoma and subsequent liver transplantation. Comprehensive genomic profiling revealed an IDH2 p. R172K mutation. Given limited treatment options and contraindications to immunotherapy, off-label treatment with the dual IDH1/2 inhibitor vorasidenib was initiated. RESULTS: The patient achieved a durable radiographic and molecular response, with a reduction in circulating tumor DNA and a partial response by RECIST criteria sustained for approximately 1 year. CONCLUSION: This case highlights the potential clinical relevance of IDH-directed therapy in IDH2-mutant cholangiocarcinoma and demonstrates feasibility in an immunosuppressed post-transplant setting. These findings are hypothesis-generating and support further evaluation of IDH inhibition in this population.
Evaluation of the efficacy of topical cosmetic products in patients with hand-and-foot syndrome undergoing oncological treatments.
Martuscelli A, Tosti G, Maisonneuve P … +5 more , Redaelli C, Indino M, Cereda M, Curigliano G, Minchella I
Oncologist · 2026 Jun · PMID 42286807 · Publisher ↗
BACKGROUND: Hand-foot syndrome (HFS) is a complication of many anticancer therapies and negatively affects patients' quality of life (QoL). Currently, little data are available on using non-pharmacological skin products...
BACKGROUND: Hand-foot syndrome (HFS) is a complication of many anticancer therapies and negatively affects patients' quality of life (QoL). Currently, little data are available on using non-pharmacological skin products as standard therapy for HFS. AIM: This study aims to investigate whether a specific set of cosmetic products is effective for managing HFS skin side effects in cancer patients. MATERIAL AND METHODS: This single-arm study involved 53 cancer patients with grade 1 of HFS undergoing chemotherapy, targeted, or hormonal treatments at the European Institute of Oncology (IEO). The study included a baseline visit and a follow-up visit 45 days later. All enrolled patients were prescribed a set of four cosmetic products for skin treatment. Patients underwent instrumental measurement to evaluate skin hydration and erythema while their QoL was assessed using the Skindex-16 self-questionnaire. Additionally, physicians clinically evaluated the HFS severity, using the CTCAE (Common Terminology Criteria for Adverse Events) scale and by comparing patient photographs. RESULTS: No patients worsened. After 45 days, the application of the cosmetic set increases skin hydration by 33% (p < 0.0001), while skin erythema decreases by 82,9% (p < 0.0001). Patients also showed a significantly lower mean Skindex-16 score at 45 days (-35.5%, p < 0.0001) compared to baseline. These findings were associated with clinical improvement in HFS-related skin symptoms in 58.5% of patients. CONCLUSIONS: These results show that a set of cosmetic products specific for cancer skin care can effectively manage HFS-related symptoms, resulting in improved QoL for patients, regardless of the anticancer treatment received.
Women's health across the reproductive lifespan in women with germline TP53 pathogenic variants: a clinical perspective.
Halpern N, Bernstein-Molho R, Peerless Y … +5 more , Kventsel I, Frenkel Z, Mizrachi Y, Shani H, Safrai M
Oncologist · 2026 Jun · PMID 42275193 · Full text
Li-Fraumeni syndrome, caused by germline TP53 pathogenic sequence variants (PSVs), is among the most penetrant hereditary cancer syndromes. With broader genetic testing and improved survivorship, more women with TP53 PSV...
Li-Fraumeni syndrome, caused by germline TP53 pathogenic sequence variants (PSVs), is among the most penetrant hereditary cancer syndromes. With broader genetic testing and improved survivorship, more women with TP53 PSVs now seek reproductive and hormonal guidance throughout their lifespan. Yet, no evidence-based framework currently exists to support women's health care in this population. In this review, we searched the available literature and found an absence of data regarding contraception, fertility preservation, pregnancy, and menopause, resulting in inconsistent counseling and both under- and overtreatment. Drawing on analogies from other high-risk cancer syndromes and our multidisciplinary clinical experience, we present interim suggestions centered on shared decision-making, individualized hormonal management, and avoiding unnecessary interventions. These findings underscore the need for prospective studies and international registries to establish evidence-based and equitable women's health care for women with TP53 PSVs.
Association between endocrine therapy and survival outcomes in estrogen receptor-low breast cancer: a systematic review and meta-analysis.
Xia F, Hu X, Zhang L … +2 more , Peng X, Xie M
Oncologist · 2026 Jun · PMID 42271640 · Full text
BACKGROUND: The clinical significance of endocrine therapy (ET) in patients with estrogen receptor-low (ER-low, 1%-10%) breast cancer remains uncertain. Increasing evidence suggests that these tumors differ biologically...
BACKGROUND: The clinical significance of endocrine therapy (ET) in patients with estrogen receptor-low (ER-low, 1%-10%) breast cancer remains uncertain. Increasing evidence suggests that these tumors differ biologically from typical hormone receptor-positive cancers, raising questions about the true benefit of ET in this subgroup. METHODS: This systematic review and meta-analysis was conducted in accordance with the PRISMA 2020 guidelines. PubMed, Embase, the Cochrane Library, and Web of Science were searched from inception to July 1, 2025. Hazard ratios (HRs) with corresponding 95% CIs for time-to-event outcomes were extracted directly or estimated from Kaplan-Meier curves when not explicitly reported. Pooled analyses were performed using random-effects models to account for between-study heterogeneity. The protocol was registered in PROSPERO (CRD420251055521). RESULTS: A total of 6 retrospective observational studies involving 8765 patients with estrogen receptor-low breast cancer were included. Endocrine therapy was associated with improved overall survival (OS) (HR 0.81, 95% CI 0.69-0.95; P = .01; I2 = 0%) and disease-free survival (DFS) (HR 0.64, 95% CI 0.45-0.90; P = .01; I2 = 0%). CONCLUSIONS: Endocrine therapy was associated with improved OS and DFS in patients with estrogen receptor-low breast cancer. These findings suggest that estrogen receptor-low breast cancer should not be uniformly considered endocrine-insensitive and that routine omission of endocrine therapy should be approached cautiously. Given that the available evidence is derived from retrospective observational studies, further prospective studies are needed to identify patients most likely to benefit from endocrine therapy.
A phase II clinical trial of albumin-bound paclitaxel, cisplatin, gemcitabine (NABPLAGEM), and paricalcitol as neoadjuvant therapy in pancreatic cancer.
Viniotis AF, Jameson GS, Wertheim BC … +18 more , Roe DJ, Lee K, Tsai FY, Gordon MS, Sharma S, Guarnieri CM, Snyder CE, Thosani AJ, Amini A, Sckolnik SE, Garrick JM, Korn RL, Rahmanuddin S, Evans RM, Downes M, Truitt M, Von Hoff DD, Borazanci EH
Oncologist · 2026 Jun · PMID 42268676 · Publisher ↗
BACKGROUND: For patients with untreated pancreatic ductal adenocarcinoma (PDAC), chemotherapy before surgery ("neoadjuvant therapy") has shown benefit in reducing recurrence and prolonging survival. Targeting the vitamin...
BACKGROUND: For patients with untreated pancreatic ductal adenocarcinoma (PDAC), chemotherapy before surgery ("neoadjuvant therapy") has shown benefit in reducing recurrence and prolonging survival. Targeting the vitamin D receptor (VDR) with analogs such as paricalcitol may improve chemotherapy effectiveness. This study evaluated the efficacy and safety of neoadjuvant albumin-bound paclitaxel (nab-paclitaxel) plus cisplatin plus gemcitabine (NABPLAGEM) plus paricalcitol (NCT03138720). METHODS: Participants were ≥18 years, had stage I-III PDAC without prior chemotherapy or radiation, Karnofsky Performance Status ≥70, and elevated CA 19-9. Study treatment included nab-paclitaxel (125 mg/m2), cisplatin (25 mg/m2), gemcitabine (1000 mg/m2), and paricalcitol (25 mcg) on days 1 and 8 of a 21-day cycle for up to 6 months. The primary outcome was CA 19-9 normalization. Secondary outcomes included margin-negative resection (R0), pathologic complete response (pCR), radiologic response, safety, and survival. Microbiome was analyzed as an exploratory outcome. RESULTS: Thirty-two participants were enrolled with median age 69.4 years, 56.2% male, and 93.8% white. Patients had resectable (cohort A, n = 10) and borderline resectable/locally advanced (cohort B, n = 22) tumors. CA 19-9 normalization occurred in 14 patients (43.8%). Two patients (6.2%) achieved pCR, and 19 (59.4%) achieved R0. Complete or partial radiologic response occurred in 39.3% of patients. Adverse events included grade 3-4 anemia (43.8%) and thrombocytopenia (59.4%). Median (95% CI) overall survival was 43.2 (7.5-upper bound not achieved) and 18.4 (10.9-41.2) months for cohorts A and B, respectively. CONCLUSION: Neoadjuvant NABPLAGEM plus paricalcitol demonstrated a high CA 19-9 normalization rate and was fairly well tolerated.
Navigating first- and second-line treatment options in HR+HER2-negative advanced breast cancer.
Sandoval J, Neven P, Emde A … +11 more , Bidard FC, Aftimos P, Llombart A, Ciruelos E, Fasching P, Li H, Campone M, Coersmeyer M, Srock S, Gnant M, Barrios C
Oncologist · 2026 Jun · PMID 42266036 · Publisher ↗
Outcomes for patients with hormone receptor-positive, HER2-negative (HR+HER2-) advanced breast cancer have improved considerably in recent years and CDK4/6 inhibitors are the preferred first-line therapy for most patient...
Outcomes for patients with hormone receptor-positive, HER2-negative (HR+HER2-) advanced breast cancer have improved considerably in recent years and CDK4/6 inhibitors are the preferred first-line therapy for most patients. Newer therapeutic classes include PI3K/AKT inhibitors, oral selective estrogen receptor degraders (SERDs), proteolysis-targeting chimeras (PROTACs), poly ADP ribose polymerase (PARP) inhibitors, and antibody-drug conjugates (ADCs). The development and regulatory approval of these new therapies to treat HR+HER2- breast cancer raises the question of how to use and sequence this fast-growing armamentarium to maximize benefit for individual patients. Disease progression and resistance mechanisms emerging on treatment (therapeutic pressure) add further complexity by inducing molecular alterations; thus, a clear understanding of the mechanisms behind resistance to both endocrine and CDK4/6 inhibitor therapies and their implications for subsequent treatment is critical. In principle, the most effective and tolerable drugs should be used first with the goals of delaying chemotherapy and offering patients the best quality and duration of life. This review aims to explain the evolving treatment landscape for HR+HER2- advanced breast cancer and provides the scientific background for developing future treatment algorithms driven by preclinical and clinical results.
Dynamic therapeutic response to osimertinib and immunotherapy in an EGFR L747S and L858R co-mutant NSCLC.
Tan Y, Wang T, Yu J … +1 more , Ouyang W
Oncologist · 2026 Jun · PMID 42249563 · Full text
BACKGROUND: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are recommended as the first-line standard treatment for advanced lung adenocarcinoma with common EGFR sensitive mutations (exon 19 E746...
BACKGROUND: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are recommended as the first-line standard treatment for advanced lung adenocarcinoma with common EGFR sensitive mutations (exon 19 E746-A750 deletion and exon 21 L858R). However, the optimal management for rare or compound EGFR mutations remains undefined. CASE PRESENTATION: We report a case of advanced lung adenocarcinoma with a rare compound EGFR L747S/L858R mutation. The patient underwent four lines of therapy, showing significant responses to alternating cycles of Osimertinib and Pembrolizumab-chemotherapy, despite intervening disease progression. The clinical course culminated in fatal treatment-induced myelosuppression, with an overall survival exceeding 43 months. CONCLUSION: This case underscores dynamic clonal evolution in advanced NSCLC: the initial L747S/L858R clone showed Osimertinib sensitivity, while subsequent resistance revealed a distinct profile (distinct TP53 mutation, MET amplification, high PD-L1/TMB) that explained the durable response to Pembrolizumab. These findings provide crucial evidence for sequential therapy strategies in compound EGFR mutations. Our findings also highlight the utility of Next Generation Sequencing (NGS) in identifying targetable resistance mechanisms, enabling prolonged survival in patients with compound EGFR mutations and offering valuable insights for clinical decision-making.
Niraparib in pancreatic cancer with germline or somatic DNA damage repair (DDR) gene alterations (BRCA and beyond): A phase II study (NIRA-PANC).
Kasi A, Al-Rajabi RMT, Baranda JC … +16 more , Saeed A, Dai J, Chalise P, Weir S, Sear B, Carroll E, Bradbury S, Tripathi A, Hyter S, Beeki V, McKittrick RJ, Kumer S, Schmitt T, Soper S, Godwin AK, Sun W
Oncologist · 2026 Jun · PMID 42249558 · Publisher ↗
BACKGROUND: Globally, pancreatic cancer is one of the leading causes of cancer-related mortalities. Although FDA-approved chemotherapy regimens are available, rapid deterioration is often observed after first-line treatm...
BACKGROUND: Globally, pancreatic cancer is one of the leading causes of cancer-related mortalities. Although FDA-approved chemotherapy regimens are available, rapid deterioration is often observed after first-line treatment. The PARP inhibitor niraparib may offer a therapeutic benefit in patients with advanced pancreatic cancer, necessitating thorough investigation. PATIENTS AND METHODS: This was an open-label, single-arm, Phase II trial involving 37 patients with metastatic or unresectable pancreatic cancer with DNA damage repair (DDR) gene alteration. Patients were administered niraparib (either 300 or 200 mg daily, based on weight and platelet count) in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal. Efficacy was assessed using the 6-month progression-free survival rate as the primary endpoint. RESULTS: Of the 37 patients, 29 were evaluated for efficacy. The 6-month PFS rate was 41.38% (12/29 patients; 95% CI 4.70%- 100%), the median PFS was 4.4 months (95% CI 3.6-6.5 months), and the median OS was 10.3 months (95% CI 7.6 -15.9 months). Further subgroup analysis revealed that the BRCA1/2 germline mutation-positive patient group (n = 14) reported a 6-month PFS rate of 50% and a median overall survival (mOS) of 12.1 months, while the non-BRCA group (n = 15) showed a 6-month PFS rate of 33.33% and a median overall survival (mOS) of 10.3 months. Adverse events occurred in 78% of patients, the most common being anemia (27%), and no treatment-related deaths were observed. CONCLUSIONS: These data demonstrate clinical activity of niraparib in patients with metastatic or unresectable pancreatic cancers harboring DDR gene defects. Future studies are warranted to establish their roles in diverse genetic patient subpopulations. CLINICALTRIALS.GOV IDENTIFIER: NCT03553004.
Transformation of ALK-translocated lung adenocarcinoma to LCNEC under alectinib treatment - a case report and mini-review.
Kim J, Stephan LU, Steinestel K … +3 more , Tamal YA, Arndt A, Barck T
Oncologist · 2026 Jun · PMID 42249553 · Full text
The histologic transformation of non-small-cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) alterations remains a rare phenomenon and a challenge for treatment with ALK tyrosine kinase inhibitors (TKI). We...
The histologic transformation of non-small-cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) alterations remains a rare phenomenon and a challenge for treatment with ALK tyrosine kinase inhibitors (TKI). We present a seldom-reported case of transformation of lung adenocarcinoma into large-cell neuroendocrine carcinoma (LCNEC) during treatment with alectinib, a second-generation ALK inhibitor, aiming to evaluate diagnostic and therapeutic approaches. The underlying mechanisms driving this transformation-likely due to a secondary resistance mechanism acquired during treatment-remain poorly understood but may involve genetic alterations, changes in the tumor microenvironment, and the emergence of additional oncogenic mutations. This case adds to the limited body of evidence and underscores the importance of recognizing neuroendocrine differentiation in ALK-positive lung cancer cases that show clinical progression. Further studies are needed to elucidate the molecular drivers of this transformation and to optimize treatment strategies for affected patients.
Hepatic Arterial Infusion Chemotherapy for Metastatic Colorectal Cancer: Real-World Outcomes of Intensification and Salvage Strategies.
Gandini A, Lipsich F, Netter-Coti J … +7 more , Lahlou W, Lepere C, Guerra X, Pellerin O, Taieb J, Boeken T, Gallois C
Oncologist · 2026 Jun · PMID 42241233 · Publisher ↗
BACKGROUND: Hepatic arterial infusion chemotherapy (HAIC) is a valuable option in patients with liver-dominant metastatic colorectal cancer (mCRC) but remains underutilized due to limited data. METHODS: We conducted a re...
BACKGROUND: Hepatic arterial infusion chemotherapy (HAIC) is a valuable option in patients with liver-dominant metastatic colorectal cancer (mCRC) but remains underutilized due to limited data. METHODS: We conducted a retrospective study of mCRC patients treated with HAIC in an expert center between 2010 and 2024. Patients were grouped according to treatment setting: intensification (INT; 1st/2nd line) and salvage (SALV; ≥3rd line). RESULTS: Among 213 patients, 99 received INT-HAIC and 114 SALV-HAIC. SALV patients had worse baseline features, including more ECOG ≥2 (16% vs 4%), RAS mutation (55% vs 45%), extra-hepatic disease (45% vs 23%), liver burden >50% (65% vs 40%), and prior IV oxaliplatin progression (41% vs 16%). Oxaliplatin was the main agent used (81% INT, 78% SALV). Objective response and disease control rate were 51%/77% (INT) and 32%/60% (SALV). Median PFS, hepatic PFS and OS were 7.6, 9, and 23 months (INT) and 3.7, 5.7, and 12 months (SALV). Prior IV oxaliplatin progression was associated with poorer outcomes of oxaliplatin-HAIC in the INT-setting. Radical liver treatment followed HAIC in 28% (INT) and 7% (SALV). Grade 3-4 adverse events occurred in 42.7% and catheter complications in 26.7%. Concomitant antiangiogenic therapy was associated with a higher rate of catheter-related complications (44% vs 22%) and remained associated after adjustment for clinical covariates. CONCLUSIONS: HAIC demonstrates promising efficacy and manageable toxicity in liver-dominant mCRC when delivered in expert multidisciplinary centers, although careful patient selection and caution with concomitant antiangiogenic therapy are warranted.
Multidisciplinary clinics in cancer-models, metrics, and meaning: a review.
Lee S, Doolin JW, Avigan DE … +21 more , Balan S, Chang P, Crowell K, Dib M, Downey K, Edmiston C, Fidias P, Freed JA, Garrett LA, Hertan L, Jalisi S, McDermott D, Messaris E, Sarpel U, Sarwar A, Shea M, Vega R, Whooley PD, Wilson JL, Mittendorf EA, Zerillo JA
Oncologist · 2026 Jun · PMID 42241230 · Full text
Few studies have been published on the existing models of cancer multidisciplinary clinics (MDCs) and no studies have conclusively compared the implications of different MDC models. We aimed to characterize MDC structura...
Few studies have been published on the existing models of cancer multidisciplinary clinics (MDCs) and no studies have conclusively compared the implications of different MDC models. We aimed to characterize MDC structural elements and reported quality measures through a narrative review of cancer MDCs in the United States. Forty-one unique MDCs were examined (8 breast, 13 gastrointestinal [GI], 8 genitourinary [GU], 4 head and neck [HN], 3 lung, 5 other cancers). MDCs were most commonly weekly (19/41) and evaluated new patients (9/41). All breast and most GU (5/8) and lung (2/3) MDCs were asynchronous whereas all HN MDCs were synchronous. Interdisciplinary discussions most frequently preceded provider visits, except for HN and other cancer MDCs. Medical, radiation, and surgical oncology were almost always included across all MDCs. The 41 unique institutional MDCs were reported across 54 studies (10 breast, 17 GI, 13 GU, 4 HN, 4 lung, 6 other cancers). Outcome measures were investigated by 38/54 (70%) studies, of which 13 reported overall survival and 6 (46%) noted a statistically significant improvement with MDCs. All lung and approximately half of GI (7/17), breast (5/10), and HN (2/4) MDCs examined a process measure. Structure and balance measures were not as widely reported. Current understanding of MDCs is based on disparate reports with significant heterogeneity in MDC structures and reported outcomes. Further investigation is needed to better elucidate the impact of MDCs in cancer care outcomes across different cancer diagnoses.
Rarity within rarity: complete response to chemoimmunotherapy in a patient with polymerase epsilon (POLE)-mutated locally advanced jejunal carcinoma.
Prisciandaro M, Morano F, Citterio D … +4 more , Flores Reyes M, Barella M, Mazzaferro V, Pietrantonio F
Oncologist · 2026 Jun · PMID 42241221 · Full text
BACKGROUND: Jejunal carcinoma is an exceptionally rare malignancy with limited therapeutic options beyond chemotherapy. Polymerase epsilon (POLE) mutations in this tumor type are even rarer, yet they may represent a pred...
BACKGROUND: Jejunal carcinoma is an exceptionally rare malignancy with limited therapeutic options beyond chemotherapy. Polymerase epsilon (POLE) mutations in this tumor type are even rarer, yet they may represent a predictive biomarker for response to immune checkpoint inhibitors in jejunal cancer and agnostically. CASE PRESENTATION: We report a 58-year-old male patient diagnosed with a POLE-mutated jejunal carcinoma. He presented with left-sided abdominal pain and was found to have an extremely large mass in the left upper quadrant. Biopsy confirmed jejunal adenocarcinoma. He was initially treated with two cycles of FOLFOX, and upon detection of the POLE mutation, nivolumab was added. After four cycles of chemo-immunotherapy, imaging demonstrated significant tumor regression. However, radiologic and clinical signs of subocclusion prompted treatment discontinuation and surgical resection. Histopathologic analysis revealed a complete pathological response, with no viable tumor cells. The patient has been disease-free since January 2025. CONCLUSION: This case underscores the role of immunotherapy in POLE-mutated tumors regardless of the site of origin and highlights the potential usefulness of molecular profiling in rare malignancies. In line with the agnostic approach used for microsatellite instability, molecular-driven clinical trials should be prioritized over histology-based studies to optimize treatment strategies for these orphan diseases.
Assessing contribution of effect in oncology combination therapies: lessons learned to inform and optimize future registrational trial designs.
Andrews HS, Agnihotram R, Blumenthal G … +20 more , Bullock J, Collins G, Doherty GJ, Farago AF, Ishii Y, Kasichayanula S, LeBlanc M, Levi-D'Ancona E, Li C, McCullough K, Morrow PKP, Navarro B, Sandhu P, Shah S, Sharon E, Su Z, Vallett C, Villalobos Y, Allen JD, Stewart MD
Oncologist · 2026 Jun · PMID 42236300 · Full text
Combination therapies can be used to significantly improve clinical outcomes in patients undergoing treatment for cancer; however, they also present challenges when establishing the contribution of effect (COE) for each...
Combination therapies can be used to significantly improve clinical outcomes in patients undergoing treatment for cancer; however, they also present challenges when establishing the contribution of effect (COE) for each component. Although factorial trials remain the most rigorous approach for determining COE, they are often impractical, such as in settings with rare cancers, aggressive disease, evolving standards of care, or monotherapy components with limited activity. As more combination regimens are co-developed from the outset, alternative approaches to registrational trial designs are needed to balance scientific rigor with feasibility and patient acceptability. Thoughtfully designed alternative approaches can support an understanding of COE when grounded in prior evidence and mechanistic understanding. Four major categories of evidence emerge to support designing combination trials without factorial arms: (1) data from trials of the same combination in other tumor types; (2) data from trials of agents with similar mechanisms of action; (3) data from early-phase or parallel trials of the combination within the same disease setting; and (4) strong mechanistic or clinical evidence that a monotherapy component lacks activity and/or imposes harm, supporting omission of inactive arms. Early regulatory engagement, prespecified decision rules, and transparent justification of design choices are essential to ensure that combination regimens provide meaningful improvement in efficacy over monotherapies while minimizing unnecessary toxicity. Applying these principles to combination therapy development can maximize patient benefit while maintaining scientific rigor.
How can integration of oncology and palliative care services be achieved for optimal patient benefit? Stakeholders' perspectives in Zimbabwe.
Nkhoma KB, Chifamba D, Chirenje ZM … +13 more , Dandadzi A, Evans CJ, Mujuru N, Mundawarara M, Mupaza L, Musaringo P, Moyo N, Mzeche S, Nyakabau AM, Tererai AC, Tsiko T, Harding R, GHAP
Oncologist · 2026 Jun · PMID 42231133 · Full text
BACKGROUND: Cancer is a main driver of death and serious health-related suffering. The growing body of evidence for early integration of palliative care alongside oncological treatment to optimizes patient-reported outco...
BACKGROUND: Cancer is a main driver of death and serious health-related suffering. The growing body of evidence for early integration of palliative care alongside oncological treatment to optimizes patient-reported outcomes is almost exclusively from high-income countries, while the greatest need is in low- and middle-income countries (LMICs). We aimed to explore the perspectives of patients, families and clinical staff on what constitutes a feasible, acceptable and appropriate model of integrated palliative and oncology care in Zimbabwe. MATERIALS AND METHODS: We conducted an exploratory qualitative study underpinned by indicators for integrated oncology and palliative care. Participants comprised healthcare professionals, patients, and families. Semistructured guides were developed and iteratively refined. Deductive framework analysis was conducted to Hui's evidence-based framework of integrated oncology and palliative care indicators. The data were then further inductively coded into the framework. RESULTS: Analysis of data from 45 stakeholders (n = 15 per group) identified 19 of 38 indicators (50%) aligned with Hui's model, indicating partial and uneven integration. Alignment was strongest in clinical processes (n = 9) and education (n = 5), with more limited support for administration (n = 3) and structure (n = 2). No findings aligned with the research domain. Inductive coding identified 3 indicators that aligned with clinical processes (routine discussion of prognosis, advance care planning and goals), clinical structure (physical environment) and education (training needs). DISCUSSION: While the Hui model is broadly applicable, substantial contextual adaptation is required. Integration cannot be achieved through coordination alone and requires system-level investment in workforce, training, infrastructure, and policy. We propose a phased "minimum package" for integration tailored to Zimbabwe and similar LMIC settings.
Reporting of primary endpoint and associated spin in randomized myeloma trials.
Singstock M, Abdul Khader AHS, Wayant C … +3 more , Lemieux M, Mainou M, Mohyuddin GR
Oncologist · 2026 Jun · PMID 42231132 · Full text
BACKGROUND: Oncology clinical trials, regardless of success in meeting their primary endpoint, often suffer from spin-the misrepresentation of research findings. Despite dramatic improvements in myeloma outcomes, numerou...
BACKGROUND: Oncology clinical trials, regardless of success in meeting their primary endpoint, often suffer from spin-the misrepresentation of research findings. Despite dramatic improvements in myeloma outcomes, numerous recent myeloma trials have failed to meet their primary endpoints while others have amplified marginally positive findings. A thorough evaluation of reporting practices and spin in myeloma randomized controlled trials (RCTs) is needed. MATERIALS AND METHODS: We performed a cross-sectional analysis of myeloma RCTs that began enrollment in January 2015 or later, with final search conducted in March 2025. Reporting of prespecified primary endpoints and sample size calculations was abstracted. Two reviewers screened for the presence of spin, defined as at least one reporting practice that could mislead readers by emphasizing benefit or minimizing unfavorable findings. Multivariable logistic regression was used to determine factors associated with spin. The methods were registered on the Open Science Framework. RESULTS: Of 82 screened studies, 71 RCTs were included. The prespecified primary endpoint was statistically significant in 46 trials (64.8%). Sample size calculations were reported in 51 trials (71.8%), and conclusions aligned with primary endpoint results in 63 trials (88.7%). Spin occurred in 25 trials (35.2%), most commonly through optimistic language and emphasis on secondary/subgroup findings. In multivariable analysis, meeting the prespecified primary endpoint was associated with lower odds of spin (adjusted odds ratio [OR] = 0.15; 95% CI, 0.03-0.70; P = .016). CONCLUSION: Spin affected one-third of contemporary myeloma RCTs and was strongly associated with nonsignificant primary endpoints, highlighting the need for primary endpoint-aligned interpretation and transparent sample size reporting.
Clinicopathologic, molecular, and treatment features of metastatic and distantly recurrent extramammary Paget disease: Mayo clinic experience.
Suleiman R, Guo R, Lohman ME … +5 more , Thome SD, Pagliaro LC, Markovic SN, Halfdanarson TR, Fuentes Bayne HE
Oncologist · 2026 Jun · PMID 42231129 · Full text
BACKGROUND: Extramammary Paget disease (EMPD) is a rare cutaneous adenocarcinoma. While localized disease has an excellent prognosis, metastatic EMPD is aggressive with no standardized systemic therapy. This study charac...
BACKGROUND: Extramammary Paget disease (EMPD) is a rare cutaneous adenocarcinoma. While localized disease has an excellent prognosis, metastatic EMPD is aggressive with no standardized systemic therapy. This study characterizes the clinicopathologic and molecular landscape of metastatic/recurrent EMPD to identify therapeutic vulnerabilities. PATIENTS AND METHODS: We conducted a retrospective cohort study of 26 patients with metastatic or distantly recurrent EMPD treated at Mayo Clinic (2000-2025). Descriptive statistics were used to summarize baseline characteristics. Survival outcomes were estimated using Kaplan-Meier methods, with group comparisons performed using log-rank testing. Continuous variables were compared using nonparametric tests, and categorical variables were analyzed using appropriate comparative tests. Pathway-level genomic correlations with TCGA reference cohorts were assessed using Spearman rank correlation. Treatment responses were retrospectively evaluated from radiologic reports. RESULTS: The cohort was predominantly male (73.1%) and White (92.3%), with a median age of 68 (IQR, 53-79). Lymph nodes were the most common metastatic site (61.5%). The median overall survival (OS) was 20.0 months (95% CI, 0-40.4). IHC showed universal CK7 and GATA3 positivity, with 80% androgen receptor (AR) expression. HER2 was positive (3+) or amplified in approximately one-third of cases. NGS revealed frequent mutations in TP53 (68.8%), ERBB2 (50%), and CDKN2A/B (50%). A "triple-hit" deletion at the 9p21 locus (CDKN2A/B/MTAP) was identified in 25% of cases. Genomic profiling showed strong similarity to HER2+ breast and urothelial carcinomas. HER2-directed therapy was associated with longer overall survival (median OS 73.0 months [95% CI, 0-177.9] vs 19.0 months [95% CI, 0-41.4]; HR 0.50 [95% CI, 0.0-177.9], P = .3), although this difference did not reach statistical significance. CONCLUSION: Metastatic EMPD exhibits distinct clinicopathologic and molecular features, including high AR and HER2 expression, TP53 and CDKN2A/B alterations, and similarity to systemic HER2+ malignancies. The observed activity of HER2-directed therapies in this cohort suggests the potential value of further investigating biomarker-guided treatment strategies in metastatic EMPD. NGS-guided profiling may inform precision treatment strategies, including AR-targeted therapy and emerging MTAP-directed approaches.
Prognostic significance of KRAS G12C versus non-G12C RAS mutations in metastatic colorectal cancer: a systematic review and meta-analysis.
Khamis MM, Lapari MS, Alkharabsheh O … +9 more , Baral MR, Sahin IH, Archwamety A, Firwana B, Patel GK, Singh A, Al Diffalha S, Manne U, Khushman M
Oncologist · 2026 Jun · PMID 42231123 · Full text
BACKGROUND: KRAS G12C mutations occur in approximately 3%-4% of metastatic colorectal cancer (mCRC) cases. While the introduction of KRAS G12C inhibitors has transformed the therapeutic landscape for this molecular subse...
BACKGROUND: KRAS G12C mutations occur in approximately 3%-4% of metastatic colorectal cancer (mCRC) cases. While the introduction of KRAS G12C inhibitors has transformed the therapeutic landscape for this molecular subset, conflicting evidence exists regarding the independent prognostic impact of this mutation in inhibitor-naïve settings. Small sample sizes and methodological heterogeneity have limited individual studies, precluding definitive conclusions. To address this knowledge gap, we conducted a systematic review and meta-analysis to establish the prognostic significance of KRAS G12C mutations in mCRC. METHODS: A comprehensive systematic literature search was conducted across PubMed, Google Scholar, and Cochrane Library through August 2025. Studies comparing overall survival between KRAS G12C and non-G12C RAS-mutant mCRC were included. Hazard ratios (HRs) were extracted or calculated from reconstructed individual patient data. Pooled analyses employed random-effects models. Quality assessment utilized the Newcastle-Ottawa Scale. RESULTS: Fourteen retrospective studies encompassing 9308 patients (903 KRAS G12C, 8405 non-G12C RAS) were included. The pooled analysis demonstrated that KRAS G12C mutations confer significantly worse prognosis, with a 28% increased risk of mortality compared to non-G12C RAS mutations (HR = 1.28, 95% CI, 1.10-1.48; p = .0015). A meta-analysis of difference in medians showed a pooled median overall survival (mOS) difference of -4.5 months (95% CI, -9.1 to 0.0; P = .05) and a pooled median progression-free survival (mPFS) difference of -1.3 months (95% CI, -2.4 to -0.1; P = .03) for KRAS G12C versus non-G12C patients. Moderate heterogeneity was observed (I2 = 54.3%). Sensitivity analysis restricted to high-quality studies confirmed these findings (HR = 1.31, 95% CI, 1.11-1.54). No publication bias was detected. CONCLUSIONS: KRAS G12C mutations represent an independent adverse prognostic biomarker in mCRC, with a statistically significant 28% increased risk of mortality compared to other RAS mutations. The consistent HR across multiple sensitivity analyses supports a true prognostic effect. These findings have important implications for patient counseling and risk stratification. While the poor prognosis may provide rationale for prioritizing trial enrollment, translation into therapeutic decision-making requires caution, as prospective data demonstrating benefit from earlier use of KRAS G12C inhibitors are lacking.
Recrudescence of a FLT3 wild-type CMML clone after allogeneic stem cell transplant for FLT3-ITD acute myeloid leukemia.
Ellaithy HA, Nardi V, Hergott CB … +1 more , Chen YB
Oncologist · 2026 Jun · PMID 42231121 · Full text
Late relapse after allogeneic hematopoietic cell transplantation (HCT) with phenotypic and molecular divergence from the original leukemia is rare. We describe a 60-year-old man with FLT3-ITD-mutated acute myeloid leukem...
Late relapse after allogeneic hematopoietic cell transplantation (HCT) with phenotypic and molecular divergence from the original leukemia is rare. We describe a 60-year-old man with FLT3-ITD-mutated acute myeloid leukemia (AML) who achieved durable remission following venetoclax-based therapy and a combined HLA-matched sibling HCT-kidney transplant with FLT3 inhibitor maintenance. Four years post-transplant, he developed chronic myelomonocytic leukemia (CMML-1) characterized by re-emergence of driver mutations without FLT3-ITD, marked loss of donor myeloid chimerism, preserved donor T-cell chimerism, and sustained renal allograft function. This case highlights a unique clinical circumstance that may function to recontextualize myelomonocytic features in AML: that they can be attributed to acute leukemias arising from clonal hematopoiesis or occult chronic malignancies, as opposed to de novo AML, particularly given the difficulty in differentiating the two in the acute leukemic setting.
KRAS-driven immune exclusion in pancreatic ductal adenocarcinoma: mechanisms and therapeutic reversal.
Kern KA
Oncologist · 2026 Jun · PMID 42226008 · Full text
Pancreatic ductal adenocarcinoma (PDAC) remains largely resistant to immunotherapy, with response rates below 5%. Emerging evidence suggests that immune exclusion in PDAC is actively maintained by oncogenic KRAS signalin...
Pancreatic ductal adenocarcinoma (PDAC) remains largely resistant to immunotherapy, with response rates below 5%. Emerging evidence suggests that immune exclusion in PDAC is actively maintained by oncogenic KRAS signaling. Mechanistic studies implicate three coordinated processes: autophagy-mediated degradation of MHC-I and impaired antigen presentation, expansion of suppressive myeloid populations, and desmoplastic stromal remodeling that restricts cytotoxic T-cell access to malignant epithelium. These barriers are at least partially reversible. Inhibition of autophagy restores surface MHC-I expression and re-enables antigen-dependent CD8+ T-cell killing. Suppression of KRAS pathway signaling remodels the myeloid compartment, alters stromal architecture, and increases intratumoral CD8+ T-cell infiltration in experimental systems. Recent studies further demonstrate that combining allele-specific KRAS inhibition with multi-arm immunotherapy can produce durable responses in resistant PDAC models. Spatial profiling data also suggest that immune architecture differs by KRAS allele, with KRAS G12D tumors more frequently exhibiting stromal T-cell segregation and KRAS G12R tumors demonstrating altered immune proximity and metabolic dependence. Together, these findings support a model in which KRAS-targeted therapy functions not only as tumoricidal therapy but also as immune conditioning of the tumor microenvironment. Translating this biologic reversibility into durable clinical benefit will require rational, barrier-specific, and allele-informed combination strategies.
KRAS G12R in pancreatic cancer: why this mutation resists current inhibitor strategies.
Kern KA
Oncologist · 2026 Jun · PMID 42226005 · Full text
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains among the most lethal solid malignancies, with limited therapeutic progress despite decades of cytotoxic chemotherapy. About 90% of PDAC tumors harbor activatin...
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains among the most lethal solid malignancies, with limited therapeutic progress despite decades of cytotoxic chemotherapy. About 90% of PDAC tumors harbor activating mutations in the Kirsten rat sarcoma viral oncogene homolog (KRAS), making oncogenic KRAS signaling a longstanding therapeutic target. Although KRAS G12C inhibitors have demonstrated clinical success in lung and colorectal cancers, this strategy has not translated to the same degree in the glycine-to-arginine substitution at codon 12 (G12R), present in 15%-20% of PDAC tumors. METHODS: A focused narrative review of the literature was conducted using PubMed and Google Scholar to examine structural, biochemical, and clinical data relevant to KRAS G12R, binding pocket dynamics, therapeutic outcomes, and novel approaches. RESULTS: G12R substitution introduces a bulky, positively charged arginine side chain that sterically occludes the binding pocket of KRAS (Switch II pocket), precluding both covalent and competitive inhibitor engagement. In addition to structural inaccessibility, G12R mutations exhibit distinct signaling rewiring, including impaired phosphoinositide 3-kinase alpha (PI3Kα) and mitogen-activated protein kinase (MEK) interactions, along with increased survival driven by amplified autophagy. These features limit the efficacy of pocket-directed inhibitors and downstream MEK blockade. Emerging pan-RAS(ON) ternary complex inhibitors bypass the occluded pocket by recruiting cyclophilin A to block effector signaling and may provide an effective means to address KRAS G12R-mutated disease. CONCLUSIONS: KRAS G12R defines a structurally and biologically distinct subset of PDAC characterized by binding-pocket occlusion and increased survival pathways. Effective treatment will require pocket-independent strategies or targeting of G12R-specific biological vulnerabilities.
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