BACKGROUND: Symptom trajectories vary among patients during cancer treatment. The National Institutes of Health resilience model, which defines resilience as the ability to resist, recover, or grow from stressors, may be...BACKGROUND: Symptom trajectories vary among patients during cancer treatment. The National Institutes of Health resilience model, which defines resilience as the ability to resist, recover, or grow from stressors, may be useful in understanding these variations. This study examined variations in symptom trajectories through the lens of resilience among older adults with advanced cancer. METHODS: This longitudinal quantitative study included patients aged 70 and older with advanced cancer who were receiving treatment regimens associated with a high risk of treatment-related toxicities, using data from the GAP70+ study (NCT02054741). A summary severity score of 24 symptoms from the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events and functional status (measured by instrumental activities of daily living) were assessed prior to the treatment regimen initiation, at 4-6 weeks, 3 months, and 6 months later. Symptom trajectories were estimated using growth mixture models. Resilience was indicated by trajectories of resisting, recovering, or growing (ie, improving from moderate/severe to none/mild severity). Its association with functional status was examined using longitudinal linear mixed models. RESULTS: The study included 710 patients (average age 77.2, 43.2% female, 88.0% receiving chemotherapy). Overall, 17.7% of patients showed resilience in symptom response, which was associated with higher baseline functional status (13.2 vs 12.0, P <.001) and stable functioning over 6 months. In contrast, non-resilience in symptom response was associated with a functional decline of 0.7-0.9 points without recovery by 6 months (P<.001). CONCLUSION: Resilience in symptom response provides a novel perspective on symptom trajectory variations. Future research should explore underlying contributing factors to inform interventions that promote resilient symptom responses.
BACKGROUND: To investigate the outcomes of combined lenvatinib plus immune checkpoint inhibitors (ICIs) in patients with unresectable, recurrent, or metastatic hepatocellular carcinoma (HCC) in a real-world setting. MATE...BACKGROUND: To investigate the outcomes of combined lenvatinib plus immune checkpoint inhibitors (ICIs) in patients with unresectable, recurrent, or metastatic hepatocellular carcinoma (HCC) in a real-world setting. MATERIAL AND METHODS: This retrospective study included patients with unresectable, recurrent, or metastatic HCC who received lenvatinib combined with ICIs at the Fifth Medical Center of the Chinese PLA General Hospital between May 2018 and November 2022. The study outcomes were overall survival (OS), progression-free survival (PFS), and treatment response. RESULTS: This study included 117 patients. The objective response rate (comprising both complete and partial responses) was 53.2%. Among those with first-line lenvatinib plus ICI (n = 109), the disease control rate (complete response, partial response, and stable disease) was 89.9%. In all patients, the median OS and PFS were 26.0 (95% CI, 22.0-30.4) and 15.3 (95% CI, 13.2-17.5) months, respectively. In first-line patients, the median OS and PFS were 27.6 (95% CI, 23.4-34.6) and 15.4 (95% CI, 13.4-18.2) months, respectively. Among the 117 patients, treatment was discontinued in 58 (50%) because of AE (n = 9, 16%), PD (n = 43, 74%), or an unknown reason (n = 6, 10%). Among the 117 patients, treatment was interrupted in 26 (22%), and the dose was adjusted in 24 (21%). CONCLUSION: This real-world study supports the possibility of using lenvatinib combined with ICI for the management of patients with unresectable, recurrent, or metastatic HCC, including first-line treatment. Confirmation through a formal clinical trial would provide firmer conclusions.
Procaccio L, Giordano G, Nichetti F
… +29 more, Milella M, Pretta A, Iacono D, Niger M, Casalino S, Vivaldi C, De Vita F, Pusceddu V, Landriscina M, Di Paolo G, Sperotto S, Masucci M, Tortora G, Bianco R, Vasile E, Zaniboni A, Miceli CC, Ongaro E, Giommoni E, Tinè G, Barsotti G, Marchesi S, Di Marco M, Ortolani S, Aprile G, Scartozzi M, Bergamo F, Melisi D, Lonardi S
BACKGROUND: International guidelines recommend 5FU/LV, Nal-IRI + 5FU/LV, FOLFIRI, FOLFOX, or (m)FOLFIRINOX as second-line (2L) chemotherapy for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) after fail...BACKGROUND: International guidelines recommend 5FU/LV, Nal-IRI + 5FU/LV, FOLFIRI, FOLFOX, or (m)FOLFIRINOX as second-line (2L) chemotherapy for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) after failure of gemcitabine+Nab-paclitaxel (GnP). However, a head-to-head comparison has not been performed. PATIENTS AND METHODS: We conducted an observational cohort study of consecutive mPDAC patients treated with 2L chemotherapy after GnP failure at 41 Italian centers. Progression-free survival (PFS) and overall survival (OS) were compared using inverse probability of treatment weighting. Interpretable artificial intelligence methods were applied to optimize treatment allocation. A counterfactual Cox model was trained on baseline characteristics to estimate 12-month PFS under each regimen, and an Optimal Policy Tree (OPT) was derived to generate treatment recommendations, validated in a test set. Net-benefit curves evaluated clinical utility. RESULTS: Among 704 eligible patients, 56 (8.0%) received 5FU/LV, 153 (21.7%) FOLFIRI, 209 (29.7%) FOLFOX, 209 (29.7%) Nal-IRI + 5FU/LV, and 77 (10.9%) FOLFIRINOX. FOLFIRINOX was associated with the longest PFS and OS. Median PFS was comparable among doublets (3.5 months FOLFOX, 3.6 FOLFIRI, 3.3 Nal-IRI + 5FU/LV), though Nal-IRI + 5FU/LV showed a long-term benefit. The OPT recommended Nal-IRI + 5FU/LV for patients with head/body tumors, Eastern Cooperative Oncology Group performance status (PS) 0, or CA19.9 < 109 U/mL in those with PS > 0. Net-benefit analysis showed that the OPT consistently outperformed uniform treatment strategies, achieving a 2.5 percentage-point net benefit at a threshold probability of ∼9%. CONCLUSIONS: FOLFIRINOX appears the most effective option for carefully selected, fit patients eligible for 2L chemotherapy after GnP failure. Interpretable artificial intelligence-derived treatment policies may provide superior net clinical benefit compared to uniform approaches and guide individualized therapy, warranting integration with upcoming targeted strategies such as RAS inhibitors.
BACKGROUND: Epigenetic regulators represent a novel strategy to modulate the tumor immune microenvironment in pancreatic ductal adenocarcinoma (PDAC). In preclinical models, DNA hypomethylating agents enhance cytotoxic T...BACKGROUND: Epigenetic regulators represent a novel strategy to modulate the tumor immune microenvironment in pancreatic ductal adenocarcinoma (PDAC). In preclinical models, DNA hypomethylating agents enhance cytotoxic T-cell infiltration, synergize with PD-1 blockade, and improve survival when combined with immune checkpoint blockade. This single-institution, phase II study evaluated the safety, efficacy, and biomarkers of azacitidine plus pembrolizumab in patients with previously treated PDAC. METHODS: Patients with locally advanced or metastatic PDAC after one prior regimen received 50 mg/m2 subcutaneous azacitidine on days 1-5 of a 28-day cycle, starting week 1, and pembrolizumab 200 mg intravenously every 3 weeks starting week 3. Baseline and on-treatment blood and tumor was collected for exploratory biomarker analysis. RESULTS: Thirty-six patients enrolled between October 2017 and September 2021 (median age: 62.5 years); 34 were evaluable for safety; 31 for efficacy. Treatment was generally well-tolerated, with Grade 1-2 fatigue and diarrhea most common AEs. Three patients (9.7%) had a partial response, and the disease control rate was 35.5%. Median progression-free and overall survival was 1.51 and 4.83 months, respectively. Exploratory analysis suggested higher baseline CD8+ T cells and lower tumor Ki-67 was associated with response, whereas low baseline CD8+ T cell and Granzyme B infiltration correlated with higher exponential tumor growth rate. PD-L1 and CD68 expression were not predictive of benefit. CONCLUSION: Azacitidine plus pembrolizumab demonstrated limited clinical activity in second line, locally advanced or metastatic PDAC. Biomarker analysis suggests higher baseline CD8+ T-cell infiltration and lower proliferative index may identify patients more likely to benefit. Clinical trial registration number: NCT03264404.
BACKGROUND: Contact days are increasingly used as a measure of time toxicity, but current measurement approaches (eg, claims data) face limitations. To determine whether participant recall of contact days could serve as...BACKGROUND: Contact days are increasingly used as a measure of time toxicity, but current measurement approaches (eg, claims data) face limitations. To determine whether participant recall of contact days could serve as a practical approach, we evaluated contact day recall accuracy among patients, care partners, and clinicians across multiple recall windows. METHODS: This single-center cross-sectional survey study enrolled adults with cancer, their informal care partner, and their primary oncologist. Participants were asked to recall the number of patient contact days and associated care burden over the prior 7, 14, 30, and 60-days. Electronic medical record (EMR) data provided gold standard contact day data. The primary outcome was recall accuracy (within ±1, ±2, ±4, and ±8 days of EMR counts across windows). RESULTS: We enrolled 42 patients, 29 care partners, and 8 clinicians. Median EMR-derived contact days were 2, 3, 7, and 11 across the 7-, 14-, 30-, and 60-day periods. Accuracy was high for all groups at 7 and 14 days (≥75%) and declined with longer windows. Participant-estimated contact days were moderately correlated with participant-assessed patient burden for patients and clinicians. We did not observe a meaningful correlation between EMR-derived contact days and patient-reported burden. CONCLUSION: A single-item patient (or care partner or clinician)-reported outcome of recalling contact days may be a practical and accurate method of determining recent contact days, particularly over shorter recall periods. The subjective recall of contact days may be more associated with burden than the exact objective contact day number.
BACKGROUND: Glioblastoma (GBM) is the most common and aggressive primary CNS tumor in adults and carries a poor prognosis. Although molecular classification has advanced, patient outcomes remain variable. Next-generation...BACKGROUND: Glioblastoma (GBM) is the most common and aggressive primary CNS tumor in adults and carries a poor prognosis. Although molecular classification has advanced, patient outcomes remain variable. Next-generation sequencing (NGS) can reveal genomic alterations that, while not yet treatment-guiding, offer prognostic and biological insight. The study aimed to investigate the association between molecular alterations in primary GBM tumors and patient survival outcomes. METHODS: This study analyzed medical records of consecutive GBM patients treated between November 1, 2018 and December 31, 2021 at a comprehensive cancer center, for whom NGS data from the tumor was available. Survival analyses were performed according to clinical, radiological, therapeutic, and molecular data. RESULTS: Of 199 patients, 38 were excluded: 15 for recurrence-only data and 23 for incomplete molecular data after first progression. In the survival analysis of the cohort (n = 161) adjusted on surgical resection, MGMT promoter methylation status, number of alterations, age, tumor localization, MIB1 and performance status, EGFR substitutions were significantly associated with increased overall survival (OS) (HR = 0.43 [0.26; 0.72], P = .001), while CDKN2A/B loss and TP53 substitutions were associated with decreased OS (HR = 1.75 [1.08; 2.84], P = .023 and HR = 1.69 [1.04; 2.74], P = .034 respectively). NOTCH1 substitutions showed a trend towards improved progression-free survival (PFS) (HR = 0.55 [0.30; 1.01], P = .054). CONCLUSION: We identified new prognostic markers in GBM, showing for the first time that EGFR substitutions improve OS. Validation in external cohorts and preclinical studies is needed.
BACKGROUND: Health-related social conditions (HRSCs) are modifiable factors affecting ovarian cancer outcomes. How best to manage HRSCs as part of ovarian cancer care remains unclear. We sought interest-holder perspectiv...BACKGROUND: Health-related social conditions (HRSCs) are modifiable factors affecting ovarian cancer outcomes. How best to manage HRSCs as part of ovarian cancer care remains unclear. We sought interest-holder perspectives on HRSC assessment and assistance to inform integration of social care with gynecologic oncology practice. METHODS: In this qualitative descriptive study, we conducted individual, semi-structured interviews with patients with ovarian cancer, their caregivers, and oncology clinicians from an academic medical center. We solicited thoughts on HRSC assessment and assistance, including whether and how HRSC discussions should occur, as well as opinions on a 20-item HRSC assessment and a community resource referral document. We analyzed data using the Rigorous and Accelerated Data Reduction (RADaR) technique. RESULTS: Participants (n = 14) included 5 patients with ovarian cancer, 4 caregivers, and 5 clinicians. Patients and caregivers were open to HRSC conversations with clinicians from various disciplines if undertaken with empathy, respect, and active listening. In addition to common HRSCs like food insecurity and housing instability, participants endorsed attending to religion/spirituality and assessing for financial hardship, interpersonal violence, psychological support, and neighborhood safety. Patients and clinicians characterized the HRSC screening questions as straightforward and in-depth. All participants felt the community resource referral document was well-organized and helpful. CONCLUSION: Even in the context of a life-threatening disease, participants affected by and caring for patients with ovarian cancer regard social conditions as relevant to cancer care. Our findings inform practical considerations of who, what, when, where, why, and how HRSC assessment and assistance can be undertaken in oncology.
BACKGROUND: Participation in cancer trials requires a commitment of time and research burden from patients. Prior work has highlighted the time burden of clinic visits during phase 1 trial participation. We extended thes...BACKGROUND: Participation in cancer trials requires a commitment of time and research burden from patients. Prior work has highlighted the time burden of clinic visits during phase 1 trial participation. We extended these findings to phase 2 cancer trials. MATERIALS AND METHODS: We reviewed a random sample of 73 phase 2 cancer trial arms with results posted on ClinicalTrials.gov 2023-2024. We extracted scheduled visit frequency and procedures from each protocol. Primary outcomes included the absolute number of planned research days (PRDs) in the first 30 days and subsequent months of participation. Secondary outcomes included procedure volume throughout the trial. We also estimated the proportion of progression-free survival (PFS) and overall survival (OS) spent in clinic. RESULTS: The median number of PRDs in the first 30 days of participating in a phase 2 trial was 5 (IQR 4-7) and 2 (IQR 1-3) per month thereafter. Across the course of a trial, patients had a median of 13 PRDs and underwent a median of 13 (IQR 10-22) blood draws, 6 (IQR 2-26) infusions, and 1 (IQR 0-2) mandatory biopsy. PRDs accounted for 10.5% of median PFS and 4.0% of median OS. The average phase 2 trial involved a cumulative 11 patient-months of planned visits. CONCLUSION: Patients in phase 2 cancer trials commit a substantial amount of time to research participation. Further work is needed to compare these estimates to time spent in standard of care and to find ways to reduce the time toxicity of trial participation.
Güzel HG, Kıvrak Salim D, Kılıçkap S
… +21 more, Kemal Y, Akosman C, Köseoğlu Ç, Coşkun A, Orman S, Efil SC, Baş O, Zeynelgil E, Çelik H, Terzi A, Karaçelik T, Karadurmuş N, Çubukçu E, Başoğlu Tüylü T, Bilgin B, Erman M, Karakaya S, Eser K, Atağ E, Karakurt Eryılmaz M, Öztürk B
AIM: IMpower133 was designed with 4 cycles of chemoimmunotherapy with atezolizumab, unlike many other studies permitted 6-cycle induction. This study aimed to compare the efficacy and safety of a 4-cycle regimen with an...AIM: IMpower133 was designed with 4 cycles of chemoimmunotherapy with atezolizumab, unlike many other studies permitted 6-cycle induction. This study aimed to compare the efficacy and safety of a 4-cycle regimen with an extended 6-cycle regimen of carboplatin, etoposide, and atezolizumab in the first-line treatment of extensive-stage small-cell lung cancer (ES-SCLC). METHODS: This retrospective multicenter study was conducted across 13 oncology centers in Turkey. A total of 181 patients with ES-SCLC who received first-line treatment with chemotherapy plus atezolizumab were analyzed and grouped into those receiving 4 cycles (n = 101) and 6 cycles (n = 80) of treatment. RESULTS: The median follow-up time was 20.9 months. The objective response rates were similar between the 4- and 6-cycle groups (79.2% vs 78.8%, P = .940). The disease control rates were also comparable (84.2% vs 86.3%, P = .940). The median progression-free survival (PFS) was 6.3 months in the 4-cycle and 8.1 months in the 6-cycle group (P = .357). The median overall survival (OS) was 16.6 months for the 4-cycle and 13.6 months for the 6-cycle group (P = .583). Intracranial progression was higher in the 4-cycle group (50.0% vs 25.5%, P = .007). Immune-related adverse events were similar between the groups. CONCLUSION: This is one of the largest real-world datasets comparing the efficacy and safety of 4 versus 6 cycles of induction chemoimmunotherapy. Although there were no significant improvements in PFS or OS, the 6-cycle regimen was associated with a lower observed rate of intracranial progression, predominantly among patients without baseline brain metastases. Further studies are needed to identify this subject in future.
BACKGROUND: Prognostic disclosure enables shared decision-making by keeping patients informed about their health and involved in treatment choices. Prognostic uncertainty is prominent in metastatic breast cancer (mBC) an...BACKGROUND: Prognostic disclosure enables shared decision-making by keeping patients informed about their health and involved in treatment choices. Prognostic uncertainty is prominent in metastatic breast cancer (mBC) and is a known barrier to prognostic disclosure, yet knowledge about prognostic disclosure in mBC has not been systematically mapped. OBJECTIVE: This scoping review aimed to explore the literature on prognostic disclosure in mBC and highlight research gaps. METHODS: We followed Arksey and O'Malley's expanded framework. Electronic databases MEDLINE (via PubMED), Scopus, PsychINFO and CINAHL were systematically searched for peer-reviewed, published journal articles. Results are reported following the PRISMA-ScR guidelines. RESULTS: The search yielded 1715 articles; ten met the inclusion criteria. Qualitative analysis identified 9 themes: Balancing Truth and Hope; Persistent Gaps Between Patient Informational Needs and Physician Responses; Using the Internet to Find Prognostic Information; the Role of Religious Beliefs; Challenges in Understanding Prognostic Information; Use of Empathy; Health Literacy and Satisfaction with Communication; Potential Harms; Structured Multidisciplinary Disclosure Interventions. Our findings suggest that the needs and preferences of patients with mBC regarding prognostic disclosure are influenced by emotional, psychological, religious, and existential factors, and change during the disease trajectory. CONCLUSIONS: Balancing truth and hope in prognostic disclosure with patients with mBC requires nuanced, emotionally attuned approaches. Clinicians could revisit patients' preferences at disease milestones or decision points. Research is needed to explore patient characteristics predicting prognostic preferences, to facilitate individualized communication, and to elucidate the impact of targeted treatments, immunotherapy, and the associated prognostic uncertainties on prognostic disclosure in mBC.
BACKGROUND: Patients with acute myeloid leukemia (AML) are still at risk of relapse after consolidation therapy with cytarabine. Therefore, early identification and intervention of patients at high risk of relapse is cru...BACKGROUND: Patients with acute myeloid leukemia (AML) are still at risk of relapse after consolidation therapy with cytarabine. Therefore, early identification and intervention of patients at high risk of relapse is crucial. METHODS: This single-center retrospective study analyzed the clinical data of 355 patients with AML (non-APL) who received cytarabine consolidation therapy. Key factors affecting relapse were identified by least absolute shrinkage and selection operator regression, and a predictive model for relapse after cytarabine consolidation therapy was constructed and internally validated. RESULTS: The study showed that age ≥50 years, female, DNMT3A mutation, TP53 mutation, IDH1 mutation, CBF-AML, white blood cell (WBC) ≥30 × 109/L, 2 courses of induction therapy, 1-2 courses of cytarabine consolidation therapy and cumulative dose of cytarabine <36 g were significantly correlated with relapse after cytarabine consolidation therapy in AML patients. Constructing a nomogram using the above factors and validating it with receiver operating characteristic, calibration curves showed that it has good discrimination and prediction. Patients were categorized into high-risk and low-risk groups based on the median risk score of the model, and there were significant differences in overall survival and event-free survival between the two groups. CONCLUSION: Predictive models based on age, sex, DNMT3A, TP53, IDH1, CBF-AML, WBC count, induction therapy course, cytarabine consolidation course, and cumulative dose can effectively assess the relapse risk after receiving cytarabine consolidation therapy in AML patients and provide a reference for clinical decision-making.
BACKGROUND: Given the superior relapse-free survival (RFS) and different safety profiles of 1 year of adjuvant S-1 or uracil/tegafur (UFT) for stage II/III rectal cancer, the benefit-risk of these 2 regimens was formally...BACKGROUND: Given the superior relapse-free survival (RFS) and different safety profiles of 1 year of adjuvant S-1 or uracil/tegafur (UFT) for stage II/III rectal cancer, the benefit-risk of these 2 regimens was formally assessed using the net treatment benefit (NTB). PATIENTS AND METHODS: Individual patient data from the Japanese Foundation for Multidisciplinary Treatment of Cancer (JFMC) 35-C1 trial were used. S-1 and UFT were compared regarding RFS, incidence of grade ≥3 symptoms, and incidence of grade ≥3 laboratory abnormalities reported as adverse events (AEs). Laboratory abnormalities and symptoms were analyzed as binary variables and as counts. Univariate and multivariate NTBs were computed for various ways of prioritizing the outcomes. RESULTS: The univariate NTB for RFS was 9.2% (95% CI, 3.4%-15.2%, P = .005) in favor of S-1. The univariate NTB was not statistically significant for any symptom. For grade ≥3 laboratory AEs, only thrombocytopenia was statistically significant in favor of UFT (NTB = -0.8%; 95% CI, -1.6% to -0.02%; P = .044). In the multivariate analysis considering RFS as the outcome of first priority, the incidence of grade ≥3 symptoms as second, and the incidence of grade ≥3 laboratory abnormalities as third, the multivariate NTB was 8.8% (95% CI, 2.7%-14.9%, P = .014) in favor of S-1. In sensitivity analyses according to age group, the NTB was generally positive for patients <70 years but nonsignificant for those ≥70 years old. CONCLUSION: The reanalysis of the JFMC 35-C1 trial suggests that S-1 has a superior benefit-risk to UFT when RFS is considered as the outcome of first priority, followed by the incidence of grade ≥3 symptoms and of grade ≥3 laboratory abnormalities.
Kiyohara H, Kondoh C, Hirota A
… +12 more, Takahashi N, Fukuda M, Kusuhara S, Nakao T, Nakajima H, Funasaka C, Harano K, Matsubara N, Naito Y, Hosono A, Niikura N, Mukohara T
BACKGROUND: Everolimus is an option for second-line or later use in combination with endocrine therapy for hormone receptor-positive breast cancer. An important everolimus-associated adverse event is drug-related interst...BACKGROUND: Everolimus is an option for second-line or later use in combination with endocrine therapy for hormone receptor-positive breast cancer. An important everolimus-associated adverse event is drug-related interstitial lung disease (ILD), reported to occur in 16.0% of individuals in the BOLERO-2 trial, and 23.5% of those in the Asian subgroup. We aimed to examine the impact of everolimus-related ILD (e-rILD) on the risk of drug-related ILD during subsequent anti-cancer treatment. PATIENTS AND METHODS: We retrospectively studied the medical records of patients with metastatic breast cancer treated with everolimus plus endocrine therapy from January 2013 to March 2022, at the National Cancer Center Hospital East. We evaluated e-rILD grade using the Common Terminology Criteria for Adverse Events version 5.0. RESULTS: A total of 115 cases were treated with everolimus; 33 (28.7%) patients developed e-rILD of any grade, including 5 (15.2%) with grade ≥3 and 2 with grade 5. Management approaches for e-rILD included dose continuation, dose interruption, prednisolone 0.5-1.0 mg/kg, and steroid pulse. The proportions of patients who received subsequent treatment were similar between the e-rILD and no e-rILD groups (73.2% [60/82] vs 81.8% [27/33], respectively; P = .567). Subsequent therapies were generally similar between the 2 groups. Drug-related ILD during regimens following everolimus occurred in one patient (3.7%) with e-rILD and 2 patients (3.3%) without e-rILD (P = .930; odds ratio, 1.12; 95% CI, 0.10-12.86). CONCLUSION: e-rILD may not influence the choice of following treatment or the development of drug-related ILD during subsequent treatments.
Torrado C, Andersen CR, Kang L
… +22 more, Brink AL, Adesoye T, Le H, Patterson CJ, Poullard A, Osburn JA, Tan HN, Gouda MA, Charles S, Urschel GE, Tang TY, Hong DS, Champiat S, Naing A, Tsimberidou AM, Dumbrava EE, Piha-Paul SA, Rodon J, Yap TA, Pohlmann PR, Meric-Bernstam F, Fu S
BACKGROUND: Telemedicine expanded rapidly during the COVID-19 pandemic, but its role in early-phase oncology trials remains uncertain. We evaluated its impact on recruitment, enrollment, equity, and access in a large pha...BACKGROUND: Telemedicine expanded rapidly during the COVID-19 pandemic, but its role in early-phase oncology trials remains uncertain. We evaluated its impact on recruitment, enrollment, equity, and access in a large phase I program. PATIENTS AND METHODS: We retrospectively analyzed patients seen for first consultation in the MD Anderson Phase I Program (2016-2023). Recruitment (consent) and enrollment (treatment initiation) were compared by visit type, race/ethnicity, and geography across pre-pandemic (2016-2019), pandemic (2020-March 11, 2023), and post-public health emergency (PHE; March-December 2023) periods. A chart review of 400 patients validated findings. RESULTS: Of 14 085 patients, 7247 were evaluated post-pandemic, with 36% (n = 2616) of first visits by telemedicine. Recruitment and enrollment rates were comparable between telemedicine and in-person visits (61.5% vs 62.6% and 37.5% vs 39.6%, respectively) in the post-2020 period. Hispanic patients used telemedicine more often than non-Hispanic (NH) white patients (43.8% vs 35.9%; P = .0002) and had higher enrollment (54.2% vs 39.4%; P < .0001) during this period. Rates were similar for NH Black vs NH White patients. Texas residents were more likely to use telemedicine than out-of-state patients (48.5% vs 22.8%; P = .0001). After the PHE ended, telemedicine increased among Texas patients (48%→56%) but declined among out-of-state patients (26%→12%). CONCLUSIONS: Telemedicine is a feasible and equitable strategy for early-phase oncology trial enrollment, with strong uptake among Hispanic patients. However, use declined among out-of-state patients after the PHE, underscoring cross-state licensure and reimbursement barriers to equitable access. Policy reforms are essential to preserve telemedicine as a permanent gateway to clinical trials and to broaden diversity in cancer research.
INTRODUCTION: Advanced cutaneous squamous cell carcinoma (cSCC) is associated with a poor prognosis. Although anti-Programmed cell Death protein 1 (anti-PD1) immunotherapy has improved cSCC management, its efficacy remai...INTRODUCTION: Advanced cutaneous squamous cell carcinoma (cSCC) is associated with a poor prognosis. Although anti-Programmed cell Death protein 1 (anti-PD1) immunotherapy has improved cSCC management, its efficacy remains limited in some patients. Second-line options, including anti-epidermal growth factor receptor (anti-EGFR) antibodies and chemotherapies, exhibit transient efficacy and often good tolerability. Given the lack of successive treatment lines, new strategies are emerging, such as the combination of anti-PD1 and anti-EGFR agents. MATERIALS AND METHODS: We conducted a retrospective, monocentric cohort study including patients treated in our oncodermatology department between 2013 and 2024 for advanced cSCC refractory to anti-PD1 monotherapy and who received a combination of anti-PD1 and anti-EGFR as second- or third-line therapy. The aim was to assess the efficacy and safety of this combination. RESULTS: Fourteen patients were included, predominantly male (12/14), with a median age of 63 years. Most tumors originated from head and neck primary sites (n = 8). Eleven patients had progressed after prior exposure to both anti-PD1 therapy and cetuximab combined with chemotherapy. Thirteen patients received cetuximab (500 mg/m2) combined with pembrolizumab every 3 weeks, and 1 received cetuximab with nivolumab. The overall response rate was 38.5%, including 15.5% complete and durable response after treatment discontinuation, observed at 9 and 16 months, and 23% partial responses. Responses occurred early, with subsequent deepening observed in 2 patients. Adverse events were mainly grade 1, and only 2 cases experienced grade 3 toxicity (acneiform rash). CONCLUSION: In a heavily pretreated real-life population with advanced cSCC, the anti-PD1/anti-EGFR combination showed clinical activity with acceptable safety, supporting its role as later-line strategy.
BACKGROUND: Programmed-cell death protein 1 (PD-1) inhibitors have become standard of care in the treatment of advanced or metastatic cutaneous squamous cell carcinoma (cSCC). However, insufficient data exists regarding...BACKGROUND: Programmed-cell death protein 1 (PD-1) inhibitors have become standard of care in the treatment of advanced or metastatic cutaneous squamous cell carcinoma (cSCC). However, insufficient data exists regarding treatment outcomes and safety among elderly patients, including patients aged >85. PATIENTS AND METHODS: We retrospectively reviewed patients aged >85 (n = 52) and compared them with two control groups: 46 patients aged 71-84 and 32 patients <70, treated with cemiplimab for cSCC. Demographics, treatment characteristics, outcomes and toxicity were evaluated. Inverse probability of treatment weighting (IPTW) was applied when comparing survival outcomes. RESULTS: Although patients >85 had worse ECOG scores and less inclined to undergo surgery, no significant differences were noted in the overall response rates (68.8% and 76.1% for <70 and 71-84, respectively vs. 73.1% for >85, P = .744) or disease control rates (75% and 82.6% for <70 and 71-84, respectively vs. 75% for >85, P = .627). After IPTW adjustment, progression-free survival (PFS) did not differ between groups (HR = 1.08, 95% CI 0.55-2.13, P = .82). Cancer specific survival (CSS) also did not differ between groups (HR = 1.05, 95% CI 0.22-4.87, P = .955). However, overall survival (OS) was shorter among patients >85 (HR = 2.64, 95% CI 1.43-4.86, P = .002). Toxicity profiles were similar, although toxicity-related deaths occurred more frequently in the >85 cohort. CONCLUSION: Cemiplimab showed comparable efficacy and tolerability across age groups, with no significant difference in PFS and CSS, but shorter OS among very elderly patients with cSCC, reflecting competing non-cancer mortality rather than reduced treatment efficacy.
Efficace F, Cannella L, Thomas X
… +21 more, Yuksel MK, Trisolini SM, Capria S, Sparano F, Baldi T, Audisio E, Maurillo L, Lemoli RM, Imovilli A, Panovska-Stavridis I, Quattrone M, Ciccone M, Filardi N, Fracchiolla N, Vallisa D, Crugnola M, Melillo LMA, Skerget M, Vignetti M, Baron F, GIMEMA, EORTC Leukemia, and EORTC Quality of Life Group
BACKGROUND: Despite improvements in survival outcomes for acute myeloid leukemia (AML), limited evidence is available on health-related quality of life (HRQoL) and health problems experienced by long-term survivors. PATI...BACKGROUND: Despite improvements in survival outcomes for acute myeloid leukemia (AML), limited evidence is available on health-related quality of life (HRQoL) and health problems experienced by long-term survivors. PATIENTS AND METHODS: This international, cross-sectional study evaluated HRQoL, comorbidities, and lifestyle behaviors among long-term AML survivors enrolled from 24 centers across 6 countries. Health-related quality of life was assessed using the SF-36 and the EORTC QLQ-C30 questionnaires, while comorbidities were measured with an adapted version of the validated self-administered comorbidity questionnaire. Lifestyle factors, including physical activity, diet, smoking, alcohol consumption, and body mass index, were also assessed. RESULTS: Overall, 225 AML survivors were enrolled, with a median time since diagnosis of 8.8 years (IQR 6.4-11.9) and a median age of 58.9 years (IQR 49.0-67.0). Compared with the general population, AML survivors exhibited clinically relevant impairments in SF-36 physical functioning (Δ = -8.09, P < .001) and role physical scales (Δ = -11.09, P < .001), as well as clinically relevant lower physical component summary scores (Δ = -3.94, P < .001). Survivors treated with alloSCT reported worse HRQoL profiles compared with those treated with autoSCT or chemotherapy only. Comorbidities were highly prevalent (88.5%), with impaired vision, back pain, and arthrosis/arthritis being the most frequent. Analysis of lifestyle behaviors showed that 66.2% of AML survivors were physically inactive, 80.2% did not meet dietary recommendations, and 55.3% were overweight/obese. Multivariate analysis identified physical inactivity as the only independent factor associated with worse HRQoL (β = -6.3, P < .001). CONCLUSION: Our study shows that AML survivors experience physical limitations and a high comorbidity burden even many years after diagnosis, and it provides insights to better inform survivorship care programs. Further research examining the relationship between physical activity and HRQoL in long-term AML survivors is warranted.