JCO oncology practice最新文献

Purpose: Cure of metastatic gastric or gastroesophageal junction cancer (mGC/GEJC) with systemic chemotherapy alone is extremely rare. Although long-term follow-up from previous phase III studies suggest that durable complete response (CR) may occur in a limited number of patients with first-line treatment, clinical characteristics of such cases remain poorly characterized.

Materials and methods: We retrospectively reviewed medical records of patients with mGC/GEJC who received systemic chemotherapy at our institute between April 2013 and March 2022. Patients were defined as having a potential cure if they demonstrated a clinical or pathologic CR, maintained progression-free survival for more than 3 years from the treatment initiation, and remained free from disease progression for at least 1 year after treatment discontinuation. Clinicopathologic features, treatment regimens, and biomarker profiles, including human epidermal growth factor receptor 2 (HER2), mismatch repair (MMR), programmed death ligand-1 (PD-L1), and claudin 18.2 (CLDN18.2), were analyzed.

Results: Fifty-one patients met the criteria for potential cure. The median age was 67 years and 72.5% of the patients were male and had single-organ metastasis. Among patients with assessable biomarker status, the proportions of positive cases were 23.5% for HER2 (n = 51), 23.3% for deficient MMR (dMMR; n = 43), 16.0% for CLDN18.2 (n = 25), and 30.0% for PD-L1 Combined Positive Score (CPS) ≥10 (n = 30). First-line therapy led to potential cure in 52.9% of patients. Ten patients were potentially cured with cytotoxic chemotherapy alone, while 23 and 26 patients received molecular targeted agents or immunotherapy, respectively.

Conclusion: The introduction of molecular targeted agents and immunotherapy has expanded the chance of potential cure. The enrichment of dMMR, HER2-positive, and CPS-high tumors among potentially cured cases highlights the urgent need to develop effective therapies for those lacking actionable biomarkers.

Purpose: The OVHIPEC-1 trial demonstrated that adding hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery (CRS) for patients with stage III epithelial ovarian cancer results in a significant increase in recurrence-free survival and overall survival. To inform policymakers about the macroeconomic budget, we conducted a budget impact analysis.

Methods: The expenditure of the Dutch health care system between 2017 and 2025 associated with the introduction of HIPEC for patients with stage III ovarian cancer eligible for interval CRS (target population) was assessed during their entire treatment course (surgical and subsequent treatment). Cost estimates are based on national registry data, national benchmark costs for hospital-related activities, list prices for drugs, therapeutic guidelines, and expert opinion. Sensitivity and scenario analyses were performed to test robustness of the analysis.

Results: The Dutch target population is expected to increase from 200 patients in 2017 to 233 patients in 2025, with 80% receiving HIPEC in 2025. Between 2017 and 2025, the impact on the annual surgical budget is €3.5 million, of which €1.8 million is directly attributable to HIPEC and its associated costs. When considering the cost of all ovarian cancer-related treatments, an additional €30,898 per HIPEC patient is spent in 2025, mainly driven by prolonged recurrence-free survival resulting in extended maintenance therapy and treatment for more platinum-sensitive recurrences. This leads to an annual total treatment budget impact of €26 million in 8 years, with €5.7 million directly associated with HIPEC use.

Conclusion: Within the Dutch health care system, the surgical budget impact of HIPEC is acceptable and falls within the boundaries for reimbursement of the responsible decision-making bodies. The total budget impact is mostly affected by the high costs of systemic treatment after prolonged recurrence-free survival due to HIPEC.

Purpose: The use of immunotherapy for cancer treatment is becoming increasingly prevalent, resulting in a growing number of patients experiencing immune-related adverse events (irAEs). Given the frequency of immunotherapy-related thyroid dysfunction (irTD), there is a growing demand for endocrine consultations, which has led to scheduling delays. This quality improvement project aimed to decrease the time to consultation and normalization of thyroid function tests (TFTs) in patients with irTD.

Methods: Using the Plan-Do-Study-Act framework, a clinic dedicated to the evaluation and treatment of irTD was created. The immuno-oncology toxicity (IOTOX) clinic is staffed by advanced practice providers (APPs) using standardized algorithms and physician support.

Results: After implementation, a prospective analysis of 46 patients from the IOTOX clinic was compared with 67 historical control patients seen before implementation. The median consultation wait time improved from 21 to 9 days (P = .01), and the median time to follow-up decreased from 180 to 58 days (P < .001). Notably, the median time to thyroid-stimulating hormone normalization was reduced from 102 to 38 days (P < .001).

Conclusion: These findings suggest that an IOTOX clinic staffed by APPs using standardized algorithms with physician support effectively improved patient access to consultation and expedited the time to normalization of TFTs. This approach can serve as a framework for addressing other irAEs at our institution and has the potential to be implemented or adapted by other institutions to improve the care of patients with irAEs.

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related death worldwide. While targeted therapy and immunotherapy have transformed first-line management, most patients without actionable genomic alterations (AGAs) will experience disease progression within the first year of their initial treatment. Here, we review pivotal trials, emerging strategies, challenges, and unmet needs for patients with advanced NSCLC without AGAs. Docetaxel with or without ramucirumab is the standard second-line therapy for patients who have progressed after platinum-based chemotherapy and immunotherapy. Targeted therapy is only suitable for patients with specific AGAs. Understanding the hallmarks of cancer immune evasion is key to developing new strategies beyond chemoimmunotherapy. The combination of antiangiogenic agents with immune checkpoint inhibitors (ICIs) has shown mixed results after progression on platinum and ICI. Bispecific antibodies, particularly ivonescimab, have shown encouraging early efficacy in this space. Artificial intelligence-driven pathomics and radiomics tools may help to refine treatment selection in the future. Chimeric antigen receptor T-cell therapy remains investigational. Patients with advanced NSCLC without AGAs who progressed after chemoimmunotherapy have limited treatment options. Novel therapies such as specific antibodies have shown promising results. Future progress will depend on the development of predictive biomarkers and understanding the mechanisms of resistance to ICIs to guide drug development.

Purpose: Rising cancer incidence and staff shortages demand more efficient outpatient oncology workflows. Pembrolizumab is conventionally administered over 30 minutes. This prospective study assessed the safety and patient experience of reducing pembrolizumab infusion duration to 10 minutes to enhance outpatient oncology workflow efficiency.

Methods: In this prospective single-center study at a large Dutch teaching hospital, adults receiving pembrolizumab for any approved indication were eligible if they had no history of grade ≥2 infusion-related reactions (IRRs). After two standard 30-minute infusions without IRRs, durations were reduced to 15 and subsequently 10 minutes. Vital signs were monitored pre- and post-infusion. Adverse events were graded per Common Terminology Criteria for Adverse Events v5.0. Pembrolizumab trough levels and patient-reported experience measures were collected. The primary end point was the incidence of grade ≥2 IRRs during shortened infusions, with safety predefined as <10%.

Results: Of 97 enrolled patients, 78 completed the protocol; discontinuation mainly resulted from disease progression or unrelated adverse events. One patient (1.1% [95% CI, 0.0 to 6.1]) experienced a grade 2 IRR during shortened infusions; no grade ≥3 IRRs occurred. Most patients reported high satisfaction, and over 150 hours of outpatient infusion unit capacity were saved.

Conclusions: Ten-minute pembrolizumab infusions are safe and well tolerated and enhance both patient satisfaction and outpatient efficiency.

Purpose: Accurate assessment of renal function is critical in the management of renal cell carcinoma (RCC), influencing surgical planning, systemic therapy eligibility, and clinical trial inclusion. Estimated glomerular filtration rate (eGFR) equations are commonly used in clinical practice but may not reflect true kidney function when compared with more accurate methods of determining renal function such as measured GFR using 24-hour urine creatinine clearance.

Methods: In this prospective study, 72 patients with nonmetastatic RCC undergoing preoperative evaluation completed serum creatinine, cystatin C, and 24-hour urine collections. eGFR values were calculated using multiple established equations, both race-inclusive and race-neutral. The agreement between eGFR and measured GFR was assessed using Passing-Bablok regression. Linear regression estimated the discrepancy between eGFR and measured GFR at clinically relevant cutoffs of 45 and 60 mL/min/1.73 m².

Results: Across all equations, eGFR consistently overestimated renal function compared with measured GFR. At a measured GFR of 45, corresponding eGFR values ranged from 53 to 59 mL/min/1.73 m²; at a measured GFR of 60, eGFR values ranged from 61 to 68 mL/min/1.73 m². The greatest overestimation was observed with race-neutral Chronic Kidney Disease Epidemiology Collaboration 2021 equations.

Conclusion: eGFR equations significantly overestimate renal function in patients with renal masses when compared with 24-hour CrCl-derived measured GFR, particularly near clinically meaningful thresholds. This misclassification may result in inappropriate exposure to potentially harmful treatments, including nephrotoxic chemotherapy and radical nephrectomy. Confirmatory measured GFR testing should be considered in patients with renal function within a ±10 mL/min/1.73 m² range of clinically significant cutoff values to ensure accurate, safe, and appropriate therapeutic decision making. Clinical guidance should specify whether physicians should use eGFR or measured GFR when determining eligibility.

Purpose: Histotripsy is a noninvasive, nonionizing, nonthermal method of treating liver tumors receiving US Food and Drug Administration (FDA) clearance in October 2023. This study aims to describe histotripsy as a method of achieving local tumor control (LTC) for primary and secondary liver tumors.

Methods: All patients receiving histotripsy since FDA clearance (December 2023-December 2024) at four institutions (two academic; two private) with >30 days of active follow-up were included. Patients were classified into palliative intent and complete treatment intent. LTC was assessed using contrast-enhanced imaging on the basis of modified response evaluation criteria in solid tumors (mRECIST) and standardized ablation criteria at postoperative days (POD) 30 and 90.

Results: Forty-seven patients received intended complete treatment to 91 liver tumors. Three total complications were observed: two cases of skin irritation treated with topical ointment and one case of bacteremia. At 30 days, 95% (n = 86/91) of treated liver tumors were nonviable. Two patients (one each with hepatocellular carcinoma and hepatic adenoma) received repeat treatment between POD30 and POD90, both converted to complete response. Forty-four patients and 85 tumors achieved 90-day follow-up. Three patients demonstrated persistently viable disease at POD90, all who had demonstrated viable tumor at POD30. Thus, the calculated primary efficacy rate at POD90 was 94% (n = 80/85), and the secondary efficacy rate was 96% (n = 82/85). The two patients with viable disease had neuroendocrine (n = 1), breast, and colorectal metastases (n = 1). Control rates were similar between primary and secondary tumors on time-to-event analysis (log-rank P = .146).

Conclusion: Histotripsy achieved high rates of LTC at 30 and 90 days in this preliminary multicenter cohort. Longer-term follow-up is needed to confirm stable results.

Immune checkpoint inhibitors (ICI) are a core mainstay of cancer care. In routine practice, the Time of Day of Administration (ToDA) of ICIs invariably is not stipulated in the clinical notes. Thus, treatment timing of administration is mainly dictated by constraints related to the organization and planning of the outpatient infusion centers, the clinical pharmacy, which reconstitutes the parenteral drugs, and the patients themselves. A growing body of evidence, recently including a prospective randomized trial, has shown a significant halving of risk reduction of an earlier death by early rather than late ToDA of ICIs in patients with 10 different advanced cancer primaries. The ToDA-dependent effect was found irrespective of the ICI type, and its use as a single agent or in combination. Similar favorable impact of early ToDA has been found on pharmacologic or clinical outcomes for a range of immunomodulated therapies including vaccines, chimeric antigen receptor T cells, and allo-HSCT. Physiologic mechanisms underpinning these clinical observations involve circadian (ie, of about a day) changes in immune cell trafficking and functions, altogether making the adaptive branch of the immune system more susceptible to pharmacologic intervention in the morning. Here, we critically discuss the available evidence, the knowledge gaps, and the impediments to deliver time-stipulated ICI in progressively busier cancer outpatient infusion centers. With numerous retrospective studies involving over 8,000 patients, we discuss consistencies and heterogeneities in these reports, including cutoff times associated with clinical benefit. We appraise the provision of care, particularly focusing on the workflows of the cancer outpatient infusion centers and the clinical pharmacy. Additionally, we propose here some practical quality improvement approaches to make morning ToDA of ICIs feasible in clinical practice.

Purpose: Patients with myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), have an increased incidence of second malignancies. This study describes the patterns, risk factors, and outcomes of second malignancies in MPN with the aim of refining our knowledge.

Methods: Using SEER database (2000-2021), we identified patients diagnosed with MPNs. The incidence, patterns, and risk factors of second malignancies including synchronous neoplasms (SYNs, within 6 months of MPN diagnosis), second primary malignancies (SPMs, after 6 months), and secondary AML (s-AML) were assessed separately. Standardized incidence ratios (SIRs) assessed the risk of SPM and s-AML in the MPN cohort compared with the general population.

Results: Among 43,930 patients with MPN, 1.6% developed SYN, 9.1% SPM, and 1.5% s-AML. Lung, prostate, breast, and colorectal cancers were most frequent solid SPMs, with lung cancer risk particularly higher in PV (SIR, 1.47) and ET (SIR, 1.23). Older age at MPN diagnosis (age 40-59 years, odds ratio [OR; 95% CI], 3.82 [3.09 to 4.78]; age 60-84 years, OR [95% CI], 6.19 [5.02 to 7.7]; ref: 18-39 years) and male sex (v female, OR [95% CI], 1.37 [1.28 to 1.46]) were associated with a higher risk of SPM. The overall SPM risk was higher than that of the general population (SIR [95% CI], 1.14 [1.11 to 1.18]; P < .05), with a particularly higher risk of hematologic SPMs (SIR [95% CI], 1.70 [1.55 to 1.85]; P < .05) and s-AML (SIR [95% CI], 19.36 [17.92 to 20.88]; P < .05). SPM development was associated with reduced median survival (125 v 184 months, P < .0001) after MPN diagnosis. s-AML progression reduced the median survival to 80, 82, and 43 months for patients with PV, ET, and PMF, respectively.

Conclusion: Patients with MPN have a higher risk of second malignancies, compared with the general population, which is associated with reduced survival. This necessitates age-appropriate cancer screening, dermatologic examinations, and long-term surveillance. Further studies are warranted to delineate the underlying factors contributing to this risk.