The activating BRAF mutation V600E occurs in 8%-12% of metastatic colorectal cancers (mCRC) and is associated with peritoneal carcinomatosis (PC) and poor prognosis. Targeted inhibition with the oral BRAF inhibitor encor...The activating BRAF mutation V600E occurs in 8%-12% of metastatic colorectal cancers (mCRC) and is associated with peritoneal carcinomatosis (PC) and poor prognosis. Targeted inhibition with the oral BRAF inhibitor encorafenib, combined with intravenous cetuximab targeting epithelial growth factor receptor (EGFR) and standard chemotherapy FOLFOX, has improved outcomes and received FDA approval in 2025 based on results from the phase III BREAKWATER trial. We report a 26-year-old male with rapidly progressive, BRAF V600E-mutant, microsatellite-stable (MSS) rectal adenocarcinoma, liver metastases, and PC presenting with bowel obstruction and inability for oral intake. To enable targeted therapy, encorafenib was administered rectally and via nasogastric tube, together with intravenous cetuximab and FOLFOX (FOLFOX+EC). Most adverse events (AEs) were present before treatment and improved during FOLFOX+EC, indicating tumor association. Severe AEs included emesis, fatigue, pain, and elevated cholestatic liver enzymes. Treatment-related AEs were manageable with anaemia (°3), neutropenia (°4), and thrombocytopenia (°1). No encorafenib-specific toxicities (rash, pyrexia, QTc prolongation, or ocular effects) were observed. Pharmacokinetic analysis showed trough plasma exposure comparable to oral dosing in patients without PC, and CT imaging at weeks 4 and 8 revealed early tumor shrinkage. This case demonstrates that rectal and nasogastric administration of encorafenib is feasible, achieves therapeutic plasma concentrations, and induces objective and clinical remission in the context of FOLFOX+EC. Short-term safety appeared manageable, though increased infection risk cannot be excluded.
Pretzell I, Fleischhauer A, Mavroeidi I
… +16 more, Prasuhn N, Kaminski K, Bender N, Grünwald V, Holly J, Hörbelt-Grünheidt T, Pakull T, Rosery V, Schürmann H, Bauer S, Siveke JT, Wiesweg M, Zimmer L, Schadendorf D, Schuler M, Benson S
BACKGROUND: Molecular Tumor Boards (MTBs) are a pillar of precision oncology, integrating results of extended molecular profiling into clinical care. Yet, their protocols are typically incomprehensible for patients. Syst...BACKGROUND: Molecular Tumor Boards (MTBs) are a pillar of precision oncology, integrating results of extended molecular profiling into clinical care. Yet, their protocols are typically incomprehensible for patients. Systematic patient-facing communication has remained limited. METHODS: In the single-center study MyCODE, individually tailored lay-language MTB protocols were developed based on didactic and psychological principles and prospectively evaluated. Using questionnaires adapted and developed for this task, patients with cancer evaluated their individual protocols and overall experience. Treating physicians were surveyed separately. RESULTS: Forty-three patients were enrolled, 33 (77%; 55% women; median age 65; patients with 10 different cancer entities) returned completed questionnaires. Of those, 82% shared the questionnaire with at least one additional person. Lay-language protocols were perceived as helpful (68% "very," 29% "rather"), well-structured (71% "very," 29% "rather"), and easily comprehensible (63% "very," 31% "rather") by most patients. 85% reported that the protocol improved their understanding of treatment decisions, and 94% perceived them as supportive even if the MTB failed to provide options for precision therapy. Additionally, 13 treating physicians received questionnaires, of which 9 were returned. Responding physicians rated the benefit for patients as high (44%) or very high (44%) and supportive (67%) or rather supportive (33%) for their personal work. CONCLUSIONS: Providing patients with lay-language MTB protocols is feasible, accepted, and valued even in the absence of therapeutic options. The MyCODE approach seems to enable patient empowerment and to support patients and physicians in shared decision-making in precision oncology.
Morrison JK, Kiefer LV, Camp A
… +18 more, Moore E, Laffan M, Adams B, Maccarone J, Kelly E, Knutsen M, Scott S, Robinson R, Huamani-Bundy J, Burns N, Haines M, Crecelius E, Sud S, Finch K, Potter J, Wheeler SB, Martin BA, Lee C
BACKGROUND: Cancer clinical trials are essential to high-quality oncology care, yet regulatory and logistical barriers have concentrated trial activity at academic medical centers, limiting access for rural and underserv...BACKGROUND: Cancer clinical trials are essential to high-quality oncology care, yet regulatory and logistical barriers have concentrated trial activity at academic medical centers, limiting access for rural and underserved populations. In 2022, 75% of U.S. counties had no active cancer treatment trials. North Carolina (NC) exemplifies these disparities, where limited local trial options, long travel distances, and socioeconomic barriers hinder participation. MATERIALS AND METHODS: To develop operational methodologies for hybrid decentralized clinical trials (hDCTs), the University of North Carolina Lineberger Comprehensive Cancer Center (LCCC) conducted an engagement initiative across nine community hospitals in NC without formal contractual research network agreements. 120 stakeholders-healthcare providers (HCPs), nurses, pharmacists, administrators, and advocates-shared insights that informed the co-development of adaptable workflows, including communication protocols, adverse event management strategies, and literacy-sensitive patient materials. Procedures were designed to align with local clinical practices and reduce burden on HCPs without requiring engagement from a regulatory standpoint. RESULTS: Visits revealed critical local resources, such as patient transportation, culturally tailored educational materials, and advocacy, that could facilitate hDCT participation. Key facilitators included motivated local champions, supportive leadership, and infrastructure for remote visits. Within 3 months, seven of nine locations initiated hDCT planning, five began patient referrals, and two enrolled patients. Early data show promising uptake and strong institutional commitment. CONCLUSIONS: hDCTs are feasible in community settings beyond traditional healthcare networks and can expand trial access by reducing logistical and financial burdens. The LCCC model offers a scalable framework to promote equity in cancer research.
BACKGROUND: Dose reduction of tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukaemia (CML) can reduce side effects and improve quality of life while maintaining treatment effectiveness and reducing...BACKGROUND: Dose reduction of tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukaemia (CML) can reduce side effects and improve quality of life while maintaining treatment effectiveness and reducing costs. OBJECTIVE: This study evaluates the views of both patients with CML and healthcare providers involved in CML care on dose reduction of TKIs. METHODS: A qualitative study with semi-structured interviews via phone or video call was conducted with Dutch adult patients with CML and their healthcare providers. The COM-B model served as a theoretical framework to guide data collection and analysis to understand participants' capability, opportunity, and motivation for dose reduction. An inductive coding approach was utilized to derive themes from the data. RESULTS: Eighteen patients and twelve healthcare providers (haematologists, nurse specialists, and pharmacists) participated, who in general were supportive of dose reduction. Two main themes were identified: (1) willingness and acceptance of dose reduction, which was shaped by participants' beliefs about the use of TKIs, the impact of TKIs on patients' quality of life, and associated hopes, fears and concerns; and (2) needs and preferences regarding dose reduction such as timing, eligibility, practical aspects, and shared-decision making. CONCLUSION: Patients and healthcare providers have positive views on TKI dose reduction to improve the burden of CML treatment. Acceptance is shaped by their beliefs and concerns, while successful implementation depends on addressing practical needs and shared-decision making.
Pancreatic cancer remains one of the most lethal malignancies, with limited integration of precision oncology into routine clinical care. We present a unique case of a RAS wild-type, MSI-H, TMB-H pancreatic ductal adenoc...Pancreatic cancer remains one of the most lethal malignancies, with limited integration of precision oncology into routine clinical care. We present a unique case of a RAS wild-type, MSI-H, TMB-H pancreatic ductal adenocarcinoma harboring a TPM3-NTRK1 fusion, monitored through 13 serial liquid biopsies over 3 years. Dynamic changes in NTRK1-fusion allele frequency, tumor mutational burden, and the emergence of an NTRK1 resistance mutation guided finely tuned, situation-adapted therapeutic adjustments: rapid disease control with targeted NTRK inhibition followed by durable remission under immune checkpoint blockade. This case highlights the power of comprehensive molecular profiling and high-frequency ctDNA monitoring to capture tumor evolution and minimal residual disease. Importantly, it further demonstrates how MRD-guided surveillance enables a precise balance between fast-acting targeted therapy and the sustained effects of immunotherapy, providing a blueprint for individualized, context-driven treatment strategies in rare molecular subtypes of pancreatic cancer.
Mezzapesa F, De Leo A, Coada CA
… +10 more, Bilancia EP, Genovesi L, Mantovani G, Ravaioli C, Turchetti D, De Biase D, Rubino D, Zamagni C, De Iaco P, Perrone AM
BACKGROUND: Chemotherapy Response Score (CRS) is a three-tier histopathologic system evaluating response to neoadjuvant chemotherapy (NACT) in high-grade serous ovarian cancer (HGSOC). METHODS: We evaluated recurrence pa...BACKGROUND: Chemotherapy Response Score (CRS) is a three-tier histopathologic system evaluating response to neoadjuvant chemotherapy (NACT) in high-grade serous ovarian cancer (HGSOC). METHODS: We evaluated recurrence patterns and survival outcomes in advanced-stage HGSOC patients treated with NACT and interval debulking surgery (IDS) between 2015 and 2024. RESULTS: Among 238 patients, CRS3 was most frequent (43.3%) and was associated higher complete cytoreduction (CC0) rates (93%) compared to CRS2 (81%) and CRS1 (57%) (p < 0.001). Median follow-up was 35 months (IQR 12.6-42.2). Median progression-free survival (PFS) was 40.4 months for CRS3, 23.4 for CRS2, and 21.5 for CRS1 (p = 0.001). Among 109 (45.7%) patients who relapsed, 25 (23%) presented with oligometastatic disease (≤5 lesions), more frequently in CRS3 (46%) than CRS2 (8.9%) or CRS1 (15%) (p < 0.001). Specifically, peritoneal (p = 0.002) and nodal (p = 0.05) oligorecurrences were more common in the CRS3 group. CRS3 predicted oligometastatic recurrence (OR = 4.89; p = 0.008) and was associated with increased use of locoregional therapies (surgery or radiotherapy) at relapse (p = 0.014). Median overall survival (OS) was 93.9, 37.2, and 31.7 months for CRS3, CRS2, and CRS1, respectively (p < 0.001). CONCLUSIONS: CRS3 predicts lower recurrence risk, increased rates of oligometastatic relapse, and greater use of locoregional treatments in patients with recurrent HGSOC after NACT and IDS.
Clinical evidence to assess the utility of routine cardiac biomarker surveillance during immune checkpoint inhibitor treatment is limited. We examined cardiac biomarkers at baseline and during initial treatment in the JA...Clinical evidence to assess the utility of routine cardiac biomarker surveillance during immune checkpoint inhibitor treatment is limited. We examined cardiac biomarkers at baseline and during initial treatment in the JAVELIN Renal 101 phase 3 trial of avelumab plus axitinib vs sunitinib in patients with previously untreated advanced renal cell carcinoma (NCT02684006). At baseline, among available patients, levels of troponin T, troponin I, B-type natriuretic peptide (BNP), and N-terminal pro-BNP were high (per local assay) in 19.8%, 1.5%, 13.0%, and 32.8%, respectively. In addition, a notable proportion of patients developed high cardiac biomarker levels during treatment in both arms. We did not find an association between elevation in cardiac biomarkers and incidence of major adverse cardiac events, although assessment was limited by the small number of events. Overall, these findings suggest that a high proportion of patients with cancer may have elevated cardiac biomarkers at baseline. Therefore, any attempt at routine surveillance of cardiac biomarkers must include testing of the same biomarker at baseline (before initiating cancer treatment).
Berrino E, Bellomo SE, Aquilano MC
… +14 more, Falcinelli M, Chesta A, Valtorta E, Zampieri D, Mauri G, Sala G, Marsoni S, Bardelli A, Sartore-Bianchi A, Siena S, Sapino A, Bonoldi E, d'Adda di Fagagna F, Marchiò C
BACKGROUND: The phosphorylated form of the histone H2AX (γH2AX), a sensor of DNA double-strand breaks (DSB), can serve as a biomarker of DNA damage and therapy response. This study aimed to evaluate the association betwe...BACKGROUND: The phosphorylated form of the histone H2AX (γH2AX), a sensor of DNA double-strand breaks (DSB), can serve as a biomarker of DNA damage and therapy response. This study aimed to evaluate the association between γH2AX expression and pathological, molecular, and immune features in colorectal cancer (CRC). PATIENTS AND METHODS: Levels of γH2AX were assessed by immunohistochemistry in a cohort of 198 CRCs, alongside immune-related markers (CD3 and CD8). A sub-cohort of 65 CRCs (26 γH2AX- and 39 γH2AX+) underwent RNA extraction and gene expression profiling using the IO360 Nanostring Panel to infer immune cell composition. Overall survival data were analyzed for exploratory correlations. RESULTS: γH2AX+ CRCs (155/198, 78%) were significantly associated with higher stage and tumor grade (P < .01). A lower γH2AX prevalence was found in MMR-deficient tumors (64%) compared to MMR-proficient cases (81%, P = .05). γH2AX+ tumors showed increased CD3+ cell infiltration in the overall population (P = .038) and in MMR-proficient CRCs (P = .028). Gene expression analysis revealed higher T-cell counts (P < .01) and reduced B-cell abundance (P < .01) in γH2AX+ CRCs. Unsupervised clustering identified 3 immune subgroups with differential γH2AX accumulation. Cluster #3, enriched in γH2AX+ tumors, displayed increased CD8+ T-cells and conferred the best survival outcome. CONCLUSION: Elevated γH2AX expression correlates with MMR proficiency, aggressive histopathologic features, and a distinctive immune-active microenvironment in CRC. These findings may support γH2AX as a marker of immune-modulated CRC subgroups with potential prognostic and therapeutic relevance.
BACKGROUND: Small cell carcinoma of the esophagus (SCCE) is a rare and aggressive malignancy lacking a standardized treatment approach. Multimodal strategies such as chemotherapy plus surgery (CT + S) or chemotherapy plu...BACKGROUND: Small cell carcinoma of the esophagus (SCCE) is a rare and aggressive malignancy lacking a standardized treatment approach. Multimodal strategies such as chemotherapy plus surgery (CT + S) or chemotherapy plus radiotherapy (CT + RT) are commonly employed, but comparative evidence remains limited and inconsistent. METHODS: We retrospectively analyzed 491 patients with pathologically confirmed SCCE from 2 independent cohorts: a Chinese single-center cohort (n = 333) and the U.S. SEER database (n = 158). Patients who received monotherapy or multimodal treatment (CT + S or CT + RT) were eligible. Overall survival (OS) was evaluated using Kaplan-Meier analysis and Cox proportional hazards models. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were applied to adjust for baseline confounders. Subgroup analyses explored potential effect modifiers. RESULTS: Multimodal therapy was associated with significantly improved OS compared to monotherapy in both cohorts (China: HR = 0.719, 95% CI: 0.561-0.922, P = .009; SEER: HR = 0.626, 95% CI: 0.417-0.938, P = .023). Among patients receiving multimodal therapy, no significant OS difference was observed between CT + S and CT + RT (P > .05), both before and after adjustment by PSM and IPTW. Subgroup analyses revealed no significant interactions between treatment strategy and clinical variables such as age, sex, tumor location, or disease stage. CONCLUSIONS: Multimodal therapy improves survival over monotherapy in SCCE. CT + S and CT + RT offer comparable effectiveness, supporting their clinical interchangeability and broader use in individualized treatment planning.
BACKGROUND: Primary brainstem lymphoma (PBSL) is rare and generally has a poor prognosis. This study aimed to analyze the clinical, therapeutic, and prognostic factors in a single-center retrospective cohort. METHODS: Fi...BACKGROUND: Primary brainstem lymphoma (PBSL) is rare and generally has a poor prognosis. This study aimed to analyze the clinical, therapeutic, and prognostic factors in a single-center retrospective cohort. METHODS: Fifty-six patients diagnosed with PBSL from January 2018 to December 2022 were retrospectively enrolled. Data on the clinical course of disease, pathological parameters, neuroradiological imaging, laboratory results, and survival data were collected and analyzed. RESULTS: The median age at diagnosis was 56 years (range: 10-77), and 23 (41.1%) patients had a Karnofsky Performance Score ≤60. The mid-brain was the most commonly involved brainstem region (35.7%). The histological type of all patients was diffuse large B-cell lymphoma. The first-line treatment was high-dose methotrexate (HD-MTX)-based chemotherapy, with an overall response rate (ORR) of 70.5%, of which 62.1% achieved complete response. For relapsed or refractory disease, radiotherapy was the most common salvage therapy and significantly improved overall survival (OS). With a median follow-up of 56 months, the median OS for the entire cohort was 30 months (95% CI 18-42 months). In both univariate and multivariate analysis, an age of ≥60 years at diagnosis was a significant prognostic factor for poor OS (hazard ratio [HR] 3.086, P = .003, 95% CI 1.467-6.492) and progression-free survival (HR 2.309, P = .030, 95% CI 1.087-4.905). CONCLUSIONS: PBSL has worse survival outcomes compared to tumors in other sites. HD-MTX chemotherapy remains effective, achieving a high ORR. Radiotherapy is an important salvage alternative for rapidly reducing brainstem lesions.
The global incidence of cancer is on the rise, with Africa experiencing a particularly steep increase in both cancer incidence and mortality. This upward trend is driven by a combination of factors, including population...The global incidence of cancer is on the rise, with Africa experiencing a particularly steep increase in both cancer incidence and mortality. This upward trend is driven by a combination of factors, including population growth, poverty, aging, urbanization, and the adoption of lifestyles that increase the risk of cancer. It is projected that from 2022 to 2045, the incidence of cancer in Africa will increase by 106.8%, while cancer mortality will rise by 111.7% if no action is taken. In contrast, Europe is expected to see increases of only 22.5% in incidence and 32.2% in mortality. Despite global advancements in cancer care, Africa continues to grapple with significant inequities in access to cancer prevention, diagnosis, and treatment. These disparities are primarily driven by financial barriers, inadequate healthcare infrastructure, and imbalances in the global pharmaceutical market. As a result, we are witnessing a troubling rise in premature deaths and their associated consequences. This paper delves into the escalating public health crisis of cancer in Africa. The authors highlight the urgent need to improve access to essential cancer medicines for all affected individuals. Additionally, the paper calls for policy reforms and a coordinated, collaborative effort among stakeholders-including governments, international organizations, and pharmaceutical companies-to ensure equitable access to treatments and improve outcomes for cancer patients in Africa. Addressing this crisis requires alignment with the sustainable development goals to prevent avoidable deaths.
Mercinelli C, Pavlick D, Agarwal N
… +14 more, Spiess PE, Li R, Kamat AM, Grivas P, Gupta S, Maiorano BA, Tateo V, Cigliola A, Piacentini M, Jacob JM, Bratslavsky G, Basnet A, Ross JS, Necchi A
BACKGROUND: the homologous recombination deficiency signature (HRDsig) is emerging as a novel potential predictor of PARP-inhibitor (PARPi) response. We compared genomic alterations (GA) across BRCA2-loss, BRCA2 short va...BACKGROUND: the homologous recombination deficiency signature (HRDsig) is emerging as a novel potential predictor of PARP-inhibitor (PARPi) response. We compared genomic alterations (GA) across BRCA2-loss, BRCA2 short variant-mutated (svmut), and BRCA2-wild type (wt) clinically advanced prostate carcinoma (CAPC) samples, combined with an assessment of HRDsig status to gain a better understanding of these biomarkers. METHODS: Comprehensive genomic profiling (CGP) was performed on 22 061 CAPC cases to evaluate all classes of GA. Microsatellite instability (MSI) status, tumor mutational burden (TMB), genomic ancestry, were derived from sequencing data. HRDsig status was calculated using genome-wide copy number features. PD-L1 expression was assessed by IHC. Comparisons were performed using Fisher's exact test with Benjamini-Hochberg correction for false discovery. RESULTS: Among 22 061 CAPC cases, 10.2% were HRDsig+. HRDsig+ and were enriched for BRCA2, RB1, MYC, RAD21, and AR alterations, while SPOP, MSI-high, high TMB, and MMR signatures were more frequent in HRDsig- cases. Across BRCA2-defined subgroups, 597 (2.7%) were BRCA2-loss, 1085 (4.9%) BRCA2-svmut, and 20 379 (92.4%) BRCA2-wt. Both BRCA2-loss and BRCA2-svmut were associated with higher GA burden and enrichment for RB1 alterations. BRCA2-loss cases displayed lower TMB-high incidence, while BRCA2-svmut showed higher MSI-high and TMB-high incidence. Most BRCA2 alterations were bi-allelic, with concurrent alterations in other HRR genes being rare. CONCLUSIONS: BRCA2-loss CAPC displays a distinct genomic landscape, marked by robust HRD features, suggesting the potential of higher sensitivity to PARPi. These findings highlight the relevance of HRDsig, and routinely use of CGP in refining patient selection for PARPi and guiding the design of future clinical trials.
Invasive lobular carcinoma (ILC) of the breast demonstrates a distinct infiltrative growth pattern and a predilection for metastasis to the gastrointestinal tract, often without forming discrete masses. We report on a 64...Invasive lobular carcinoma (ILC) of the breast demonstrates a distinct infiltrative growth pattern and a predilection for metastasis to the gastrointestinal tract, often without forming discrete masses. We report on a 64-year-old woman with a history of estrogen receptor-positive, human epidermal growth factor receptor 2-negative ILC who presented with progressive nausea, vomiting, and diarrhea. Recent surveillance imaging had shown no evidence of metastatic disease. Computed tomography revealed nonspecific findings despite extensive mucosal involvement that was later identified on endoscopy. Upper endoscopy and colonoscopy demonstrated diffuse nodular and congested mucosa throughout the duodenum and colon without focal lesions. Histologic evaluation revealed poorly cohesive tumor cells infiltrating the lamina propria, and immunohistochemistry was positive for cytokeratin 7, GATA3, and estrogen receptor, confirming metastatic breast carcinoma. Diffuse gastrointestinal involvement by ILC is uncommon and may mimic inflammatory, infectious, ischemic, or medication-related conditions, contributing to delayed diagnosis. This case highlights an important diagnostic pitfall and underscores the need to consider metastatic disease in patients with a history of lobular breast carcinoma who present with unexplained gastrointestinal symptoms, even in the absence of radiographically apparent disease.
BACKGROUND: The first-generation Bruton's tyrosine kinase inhibitor (BTKi), ibrutinib, is associated with significant cardiotoxicity. Second-generation agents were developed to mitigate this risk and offer an improved sa...BACKGROUND: The first-generation Bruton's tyrosine kinase inhibitor (BTKi), ibrutinib, is associated with significant cardiotoxicity. Second-generation agents were developed to mitigate this risk and offer an improved safety profile. This systematic review and meta-analysis of six direct comparator studies compares the cardiac safety profiles of first- and second-generation BTKi. METHODS: We systematically searched Medline, Embase, and Cochrane for studies directly comparing first- and second-generation BTKi. Data from 6 studies, encompassing 14 455 patients (12 816 in the first-generation arm and 1639 in the second-generation arm), were included. The primary outcomes were the incidence of atrial fibrillation (AF) and cardiac events, defined by the Medical Dictionary for Regulatory Activities system organ class. All pooled analyses were conducted using a random-effects model. Publication bias was evaluated visually using a funnel plot, quantitatively with Egger's regression test, and corrected using the Duval and Tweedie trim-and-fill method. RESULTS: Compared to second-generation agents, ibrutinib was associated with a significantly higher risk of AF (OR 2.50, 95% CI, 1.97-3.17), total cardiac events (OR 1.53, 95% CI, 1.18-1.99), and heart failure (OR 2.08, 95% CI, 1.13-3.83). This translated to a 3-fold higher rate of treatment discontinuation for a cardiac cause (OR 3.32, 95% CI, 1.46-7.55). No significant difference in all-cause mortality was found. CONCLUSION: Second-generation BTKi may provide a more favorable cardiovascular safety profile than ibrutinib, resulting in fewer key cardiac events and less treatment-limiting toxicity. These findings should inform clinical decision-making, especially for patients with increased risk for cardiovascular disease.
BACKGROUND: Cytogenetic abnormalities (CAs) in multiple myeloma (MM) are traditionally assessed statically at diagnosis, but longitudinal monitoring reveals dynamic clonal evolution, particularly during relapse. In Asian...BACKGROUND: Cytogenetic abnormalities (CAs) in multiple myeloma (MM) are traditionally assessed statically at diagnosis, but longitudinal monitoring reveals dynamic clonal evolution, particularly during relapse. In Asian populations, data on CA dynamics and their prognostic impact remain scarce. PATIENTS AND METHODS: This retrospective study included 106 MM patients (2014-2024) in whom CAs were evaluated at diagnosis and relapse via cIg-FISH. The prognostic impact of clonal burden, copy number alterations, and longitudinal evolution of cytogenetic complexity was comprehensively assessed. RESULTS: At first relapse, 33.0% of patients acquired new CAs, with 1q21+ and del(17p13) incidences significantly increasing (P = .032, P = .003). Longitudinal analysis showed 1q21 amplification (≥4 copies) expanded (27.4%-40.6%), while gain (3 copies) remained stable. Baseline 1q21 amplification predicted shorter 1st PFS (P = .002), whereas 1q21 gain at relapse correlated with inferior 2nd PFS (P = .023), often co-occurring with del(17p13) (28.1%). Persistent 1q21+ and de novo del(17p13) both predicted inferior OS (P < .05). Based on clonal dynamics, patients with >20% expansion exhibited significantly shorter 1st PFS (P = .045) compared to the stable (unchanged) CAs subgroup. Similarly, those acquiring new CAs had shorter 2nd PFS (P = .039) and a trend toward worse OS (P = .056). CONCLUSION: Both acquisition of new CAs and expansion of existing clones at relapse are key prognostic indicators, highlighting the importance of dynamic CA monitoring in MM management.
Lim M, Grandhi N, Shah P
… +14 more, Raghav K, Serpas V, Morelli MP, Pedersen K, Kalyan A, Salem M, Huey R, Shen JP, Wang H, Wang H, Vinocha A, Thomas J, Wolff R, Overman MJ
BACKGROUND: Small bowel adenocarcinoma (SBA) is molecularly distinct from colorectal and gastric cancers, yet treatment typically parallels colorectal cancer. We evaluated the activity of taxane-based therapy in the larg...BACKGROUND: Small bowel adenocarcinoma (SBA) is molecularly distinct from colorectal and gastric cancers, yet treatment typically parallels colorectal cancer. We evaluated the activity of taxane-based therapy in the largest SBA cohort to date. METHODS: We retrospectively reviewed SBA patients treated with taxane-based chemotherapy at MD Anderson Cancer Center from 1994 to 2024. Eligible patients had pathologic confirmation, received >1 treatment cycle, and had tumor response evaluation. Survival analyses were analyzed using Kaplan-Meier and Cox proportional hazard models. RESULTS: Seventy patients were identified. Median age was 57, and 59% were male. Primary sites were duodenum (44%), jejunum (34%), and ileum (16%). Metastatic sites included peritoneum (39%) and liver (31%). Common mutations were TP53 (63%), KRAS (47%), SMAD4 (24%), and APC (15%). Taxanes were administered as single agents (29%) or in combination (71%), most often in second- (40%) or third-line (33%) settings. Overall response rate was 24%. Median time to progression (mTTP) was 3.1 months (95% CI: 2.0-4.2) and median overall survival (mOS) was 8.7 months (95% CI: 7.4-10.1). Efficacy did not differ by treatment line, regimen type, or tumor site, but was significantly associated with TP53 status; response rate was 20% in TP53-mutated vs 45% in wild-type (P = .009), with mTTP 2.5 vs 4.9 months (P = .009) and mOS 7.3 vs 10.6 months (P = .002). On multivariable analysis, TP53 mutation predicted worse outcomes. CONCLUSION: Taxane-based therapy demonstrated activity in metastatic SBA, with 24% response and 3.1-month mTTP. TP53 mutation may be a negative predictive marker for taxane efficacy. These findings support prospective investigation in metastatic SBA.
BACKGROUND: Exocrine pancreatic insufficiency (EPI), a common complication of pancreatic cancer (PC), reduces quality of life and may shorten survival. While pancreatic enzyme replacement therapy (PERT) improves symptoms...BACKGROUND: Exocrine pancreatic insufficiency (EPI), a common complication of pancreatic cancer (PC), reduces quality of life and may shorten survival. While pancreatic enzyme replacement therapy (PERT) improves symptoms and outcomes, real-world patterns of EPI workup and PERT use across PC subtypes remain poorly described in the United States. PATIENTS AND METHODS: We retrospectively analyzed 250 patients with resectable or metastatic PC from a single institution's prospectively maintained registry (2013-2018), collecting data on clinical characteristics, EPI symptoms, fecal elastase testing, and PERT prescriptions. In addition to the retrospective analysis, a quality improvement intervention for EPI management was implemented (1/2021-1/2023), and outcomes were analyzed. RESULTS: Among 250 patients, 97 underwent surgery for resectable disease and 153 received non-surgical management for metastatic PC. Exocrine pancreatic insufficiency symptoms occurred in 58% of metastatic and 68% of surgical patients. Fecal elastase testing was rarely performed (2% vs 9%, respectively). Pancreatic enzyme replacement therapy was prescribed to 46.5% of metastatic and 84% of surgical patients, but average doses were suboptimal (18 500 vs 20 000 USP units per meal; recommended: ≥40 000). Among those on PERT, symptom resolution was reported in 33% of metastatic and 44% of surgical patients. Contrasting with results from the retrospective analysis, the quality improvement intervention led to 90% of 41 participants being prescribed PERT at an average dose of 44 700 USP units per meal. Treated patients (74.1%) experienced complete resolution of EPI symptoms. CONCLUSION: Despite prevalent EPI symptoms in PC patients, fecal elastase testing was infrequently utilized, and PERT was often underdosed. Educational initiatives are needed to improve guideline adherence and optimize outcomes.