Cancer

Background Despite palliative‐intent interventions’ ability to improve the quality of life of patients, significant inequalities persist in uptake. Such disparities are characterized by racial, socioeconomic, and geographic factors. However, less is known among disaggregated Hispanic populations. This study examines disparities in the receipt of palliative‐intent interventions among Hispanic subgroups with advanced lung, breast, and prostate cancer. Methods Via the National Cancer Data Base, data were collected on the receipt of palliative‐intent interventions among Hispanic subgroups diagnosed with American Joint Committee on Cancer analytic stage IV breast, lung, and prostate cancer between 2004 and 2021. Multivariate logistic regressions were conducted to quantify differences in the uptake of palliative‐intent care among Hispanic subgroups. Results Among 945,894 total patients, disaggregated analyses revealed reduced receipt of palliative‐intent interventions for patients with lung, breast, and prostate cancer of Mexican descent (lung, p < .001; breast, p < .001; prostate, p = .03) compared to non‐Hispanic White patients. Receipt for patients of South or Central American descent was reduced in comparison to non‐Hispanic White patients for lung and breast cancer (lung, p < .001; breast, p < .001). Uptake of palliative interventions for metastatic lung and breast cancer was reduced for patients of Cuban descent (lung, p < .001; breast, p = .03), and was lower for patients of Dominican descent with breast cancer, compared to non‐Hispanic White patients (p = .05). Conclusions These findings demonstrate disparities in the receipt of palliative‐intent interventions among disaggregated Hispanic subgroups. This study highlights the need for disaggregated research to further characterize these disparities and their drivers. Community‐level and patient‐centric efforts may help to address these inequities.

This news section offers Cancer readers timely information on events, public policy analysis, topical issues, and personalities. In this issue, interim analyses showed significantly better progression‐free survival outcomes with the combination regimen versus either chemotherapy alone or nivolumab alone for the first‐line treatment of metastatic colorectal cancer. Also, omitting axillary surgery for patients with low‐risk breast cancer and breast‐conserving therapy had no negative impact on the course of disease, and subcutaneous daratumumab significantly lowered the risk of progression to active multiple myeloma or death.

Background Adenoid cystic carcinoma (ACC) frequently has pulmonary metastasis (PM). Given limited systemic therapy options, these metastases are often treated with pulmonary metastasis–directed local therapy (PM‐LT), although with unknown impact on overall survival (OS). This single institution, retrospective cohort study investigated the survival outcomes of PM‐LT versus no PM‐LT in ACC. Methods ACC patients with at least one PM (≥5 mm) were included. PM‐LT was metastasectomy or radiotherapy. Clinicopathologic characteristics were compared between patients with and without PM‐LT. Primary end point was OS from PM diagnosis, with landmark analysis at 6 months, 1 year, 2 years, and 3 years after metastasis diagnosis, with Cox proportional hazards model multivariate analysis and propensity score matching analysis. Subgroup analysis by ACC histology (solid/nonsolid) was performed. Results Of 219 included ACC, 119 (54%) had no PM‐LT and 100 (46%) did. PM‐LT patients had more nonsolid histology (p = .0008), oligometastases (p < .0001), exclusively PM (p = .02), and longer time to metastasis from diagnosis (p < .0001). On univariate analysis, PM‐LT by 6 months, 1 year, and 2 years, but not by 3 years, increased OS. On multivariate analysis, PM‐LT by 6 months (p = .12), 1 year (p = .08), or 3 years (p = .08) did not significantly increase OS, but PM‐LT by 2‐years had a borderline statistically significant association (p = .045). Of the 104 nonsolid ACC, 50 underwent PM‐LT and 54 did not. On univariate and multivariate analysis, PM‐LT did not increase OS at any time point for nonsolid ACC. Conclusion This is the largest study of survival outcomes of PM‐LT in metastatic ACC. Findings suggest PM‐LT does not increase OS in unselected ACC.

Background Emerging research suggests that lesbian, gay, bisexual, and queer (LGBQ) women face barriers to breast cancer screening. The authors sought to quantify sexual identity disparities in mammography screening, health care access, and lifestyle‐related risk factors using two national surveys. Methods Data from the 2018, 2019, and 2021 National Health Interview Survey (NHIS) and the 2018, 2020, and 2022 Behavioral Risk Factor Surveillance System (BRFSS) survey were analyzed. The authors performed meta‐analyses to determine the relative risks (RRs) of self‐reported, up‐to‐date mammography for women identifying as LGBQ versus those identifying as straight. Differences in health care access and lifestyle‐related breast cancer risk factors were also assessed by sexual identity. Results LGBQ women reported lower up‐to‐date mammography (pooled RR [pRR], 0.95; 95% confidence interval [CI], 0.92–0.98) versus straight women, driven by differences among bisexual/queer women (pRR, 0.91; 95% CI, 0.87–0.95) and those entering screen‐eligibility at ages 40–49 years (pRR, 0.86; 95% CI, 0.80–0.91) and 50–59 years (pRR, 0.93; 95% CI, 0.88–0.98). LGBQ women were more likely than straight women to be uninsured (BRFSS survey [8.6%; 95% CI, 6.5%–11.2%] vs. NHIS [5.1%; 95% CI, 4.8%–5.4%]) and to experience financial barriers to care (BRFSS survey [13.8%; 95% CI, 11.6%–16.3%] vs. NHIS [8.9%; 8.5%–9.2%]). Lifestyle‐related breast cancer risk factors were more common among LGBQ women versus straight women, including current smoking (BRFSS survey [19.0%; 17.1%–21.2%] vs. NHIS [13.9%; 13.6%–14.3%]). Conclusions LGBQ women were more likely than straight women to be exposed to breast cancer risk factors, which were compounded by lower screening and facing health care access barriers. It is crucial to identify interventions for screening and risk reduction that are accessible and effective for LGBQ women, particularly bisexual/queer women and those aging into screen‐eligibility.

Background Prognosis after salvage allogeneic hematopoietic cell transplantation (HCT) in refractory myeloid malignant diseases is poor with no standard of care. Methods A prospective single‐arm study was conducted to evaluate if a combination of posttransplantation bendamustine and cyclophosphamide (PTBCy) facilitates augmented graft‐vs‐leukemia effect in this group of patients. The prospective study (NCT04943757) of HCT from all types of donors enrolled 50 patients with refractory myeloid neoplasms. Results Cumulative incidence of engraftment was 88%; 76% had no measurable residual disease. Immune toxicity in the form of cytokine release syndrome was observed in 30%. Cumulative incidence of acute graft‐vs‐host disease (GVHD) Grade 2 through 4 was 20%. Cumulative incidence of moderate and severe chronic GVHD was 34%. Nonrelapse mortality was 20%. Relapse incidence was 62%, but median time to relapse was 245 days. Overall survival was 33% and event‐free survival was 22%. In the multivariate analysis of event‐free survival alternative donor (hazard ratio, 0.24; 95% CI, 0.11–0.52) and adverse genetic features (hazard ratio, 2.48; 95% CI, 1.26–4.88) were significant. PTBCy regimen was associated with unique immune reconstitution pattern with high levels of CD8+ effector memory T cells, PD‐1L–positive monocytes, and granulocytes. Conclusions PTBCy GVHD prophylaxis is a promising approach for refractory myeloid neoplasms, which delays relapse after HCT and opens the window for posttransplant prophylaxis.

Treatment‐free remission may now be an option for patient with Philadelphia chromosome‐positive acute lymphoblastic leukemia. Stopping therapy for medical reasons has indicated that this can be successful in several patients.

Background The combination of anlotinib with chemotherapy has demonstrated encouraging efficacy in the treatment of nonsmall cell lung cancer (NSCLC). The objective of this phase 1/2 trial was to establish the maximum tolerated dose of anlotinib in combination with docetaxel and to assess the efficacy and safety of this regimen in patients with advanced NSCLC who had progressed after platinum‐based chemotherapy. Methods In the phase 1 trial, eight patients were enrolled to determine the maximum tolerated dose, which was identified as 10 mg for anlotinib in combination with docetaxel. In the phase 2 trial, in total, 88 patients were randomized, with 57 receiving anlotinib at the established maximum tolerated dose alongside docetaxel and 31 receiving docetaxel monotherapy. Tumor response was evaluated in 88 patients. Results In the phase 2 study, the combination of anlotinib and docetaxel demonstrated a significant improvement in progression‐free survival compared with docetaxel monotherapy (median, 5.39 vs. 2.56 months; hazard ratio, 0.36; 95% confidence interval, 0.21–0.63; p = .0002). The objective response rate was also superior in the combination group (26.32% vs. 6.45%). The median overall survival was 16.82 months for the combination group versus 9.86 months for the monotherapy group (hazard ratio, 0.89; 95% confidence interval, 0.47–1.66; p = .7114). Safety analysis included 96 patients, and the most frequent treatment‐emergent adverse events were decreased neutrophil count and decreased white blood cell count. Conclusions The addition of anlotinib to docetaxel was characterized by a manageable safety profile and also resulted in a significant improvement in progression‐free survival among patients with advanced NSCLC who had previously failed platinum‐based chemotherapy (ClinicalTrials.gov identifier NCT03726736).

Background The use of opioids and its benefits and harms among cancer survivors are poorly understood. The authors examined opioid use and related outcomes among adolescent and young adult (AYA) cancer survivors after cancer treatment. Methods The authors identified 2‐year cancer survivors diagnosed between 15 to 39 years of age at Kaiser Permanente Southern California (2000–2012, followed through 2019). Individuals without cancer were matched to survivors on age, sex, and calendar year for comparison. The authors used robust Poisson regression to compare long‐term (≥90 days) opioid use during follow‐up and Fine‐Gray hazard models to compare incident long‐term high‐dose use (≥50 morphine milligram equivalents daily dose ≥90 days), benzodiazepine co‐use, opioid use disorder (OUD), opioid overdose, and opioid‐related hospitalization. We also restricted analyses to individuals on long‐term opioid therapy, and evaluated risk factors for opioid‐related outcomes within cancer survivors. Results Of 5908 AYA cancer survivors and 81,833 noncancer individuals, 5.2% and 1.8% had long‐term opioid use during follow‐up, respectively (prevalence ratio = 1.8, 95% confidence interval, 1.6–2.0). Cancer survivors had higher incidence of long‐term high dose opioid use (hazard ratio [HR] = 2.2 [1.8–2.8]), benzodiazepine co‐use (HR = 1.4 [1.3–1.5]), and opioid‐related hospitalization (HR = 1.5 [1.1–2.2]) compared with noncancer individuals. Among those on long‐term opioid therapy, cancer survivors had elevated risk for long‐term high dose use (HR = 1.4 [1.1–1.8]) and benzodiazepine co‐use (HR = 1.6 [1.2–2.1]), but lower OUD risk (HR = 0.6 [0.4–0.9]). Opioid use during cancer treatment phase most strongly predicted long‐term high dose use and OUD/overdose during survivorship. Conclusion Findings call for risk‐stratified patient monitoring and better understanding of the differential OUD risk in AYA cancer survivors.

Background In clinical trials, adding bevacizumab to first‐line (1L) chemotherapy for Stage III/IV epithelial ovarian cancer significantly improved progression‐free survival but not overall survival (OS). Post hoc analyses suggested potentially greater benefit from the addition of bevacizumab in patients with high‐risk prognostic factors. Methods Eligible patients in this nationwide, deidentified, electronic health record–derived database study had Stage III/IV epithelial ovarian cancer and initiated 1L chemotherapy ± bevacizumab (January 1, 2017–May 31, 2023). High‐risk prognostic factors were defined as having Stage IV disease or Stage III disease with either visible residual disease or no documentation of surgery. Median real‐world time to next treatment and real‐world OS, indexed to 1L initiation, were estimated by Kaplan–Meier methods. Cox proportional hazards models assessed associations between patient characteristics and 1L treatment received, with each real‐world outcome. Results Among 1752 patients, median (interquartile range) age was 68 (60–75) years; median (interquartile range) follow‐up time was 18.5 (8.0–36.6) months. Among patients with high‐risk prognostic factors, median (95% CI) real‐world time to next treatment was significantly longer with 1L chemotherapy plus bevacizumab (13.6 [12.7–15.9] months) than chemotherapy alone (11.7 [10.6–12.6] months; p = .032). There was a trend toward longer median (95% CI) real‐world OS with 1L chemotherapy plus bevacizumab (31.1 [27.7–37.5] months) versus chemotherapy (27.4 [25.1–31.2] months; p = .052). For patients without high‐risk prognostic factors, real‐world outcomes did not differ with the addition of bevacizumab. Conclusions These real‐world results support clinical trial data suggesting the benefit of adding bevacizumab to 1L chemotherapy may be limited to patients with high‐risk prognostic factors.

Background Persistent area‐level poverty may be associated with long‐term social and economic disinvestment, which can contribute to social risks and financial difficulties for individuals. This study examines the associations between census tract poverty and the prevalence of social risks and financial hardship among Black cancer survivors. Methods Data were used from 4066 participants in the population‐based Detroit Research on Cancer Survivors cohort. Census tract poverty was categorized as persistent (≥20% of residents in poverty for 30+ years), current (≥20% currently in poverty), and low (<20% in poverty). Participants self‐reported social risks related to food, housing, utilities, access to care, and safety as well as material and behavioral financial hardship. Prevalence ratios and 95% confidence intervals (CIs) were estimated with modified Poisson models controlling for sociodemographic and cancer‐related factors. Results Overall, 36% of participants reported any social risks. The prevalence was higher in persistent (45%) relative to both current (40%) and low‐poverty areas (25%). The prevalence of each social risk and of behavioral financial hardship was higher in current and persistent versus low‐poverty areas in unadjusted models but most attenuated in adjusted models. The adjusted prevalence of any social risk was 21% higher in both persistent (95% CI, 7%–37%) and current (95% CI, 7%–36%) compared with low‐poverty areas. Area poverty was not associated with financial hardship in adjusted models. Conclusions Living in current but not persistent or persistent high‐poverty areas is associated with a higher prevalence of social risks. Residents of high‐poverty areas may represent a priority population for screening and intervention.

Background Colorectal cancer (CRC) screening disparities persist among populations with limited health care access. Although Medicaid expansion and paid sick leave could address these barriers, there is limited data on the combined impact of these policies and CRC screening. Methods The authors conducted a difference‐in‐differences analysis using 2012–2018 Behavioral Risk Factor Surveillance System data. The study population included adults 50–75 years of age meeting preventive cancer screening guidelines during the study period. States were categorized into three groups: those with Medicaid expansion and paid sick leave (ME + SL), Medicaid expansion without paid sick leave (MEnoSL), and neither policy (NoME/NoSL). The pre‐policy period was 2012–2014 and the post‐policy period was 2015–2018. The outcome was the percent up‐to‐date with CRC screening. Survey‐weighted logistic regression models accounted for individual‐ and state‐level covariates and state‐clustered standard errors. Results Post‐policy implementation, CRC up‐to‐date screening was 2.9 percentage points greater in ME + SL states compared to MEnoSL states (p < .001) and 4.2 percentage points greater compared to NoME/NoSL states (p = .018). These changes correspond to an estimated 352,343 and 1,087,140 fewer missed screenings between ME + SL and MEnoSL and NoME/NoSL states, respectively. The increased percent of up‐to‐date CRC screenings was associated with a reduction in colorectal cancer deaths: 8456 from ME + SL versus MEnoSL and 26,091 from ME + SL versus NoME/NoSL. Conclusions Medicaid expansion combined with paid sick leave was associated with a greater likelihood of being up‐to‐date with CRC screening compared to Medicaid expansion alone or neither policy.

Background By leveraging a natural experiment afforded by New York’s 2009 policy restricting Medicaid reimbursement for breast cancer surgery at low‐volume hospitals, this study examined the effect of regionalization on time from breast cancer diagnosis to initial upfront surgery. Methods By using a linked data set merging New York Cancer Registry and New York facilities’ discharge data, women with stage I–III incident breast cancer during the pre‐ (2004–2008) and postpolicy (2010–2013) periods were identified. Multivariable difference‐in‐difference‐in‐differences models estimated the policy effect on the probability of experiencing delayed care (>60 days) between diagnosis and initial surgery. Results Among 71,135 women, 12% had Medicaid coverage. Women treated in postpolicy years (p < .001 relative to prepolicy) and Medicaid beneficiaries (p < .001 relative to non‐Medicaid patients) were more likely to experience delayed care. Non‐Medicaid beneficiaries had a 12.6% probability of delayed care postpolicy (compared to 8.8% prepolicy), whereas Medicaid beneficiaries had a 21% probability of delayed care postpolicy (compared to 14.5% prepolicy). Although these increases were not statistically different between the Medicaid and non‐Medicaid groups as a whole, which indicates no overall policy effect, Medicaid beneficiaries in nonurban areas were more likely to experience delayed care after the policy implementation (p = .04). Conclusions Regionalization of breast cancer care in New York did not lead to a significant overall decrease in access to timely surgical care. Regionalization of care may be a promising approach to improving breast cancer outcomes. However, the potential impact on nonurban and other vulnerable populations must be carefully considered to prevent exacerbating disparities in access to care.

PD‐(L)1–based immune checkpoint inhibitor therapies have profoundly impacted the treatment of many solid malignancies. Although the addition of CTLA‐4 checkpoint inhibitors can enhance anticancer activity, it also significantly increases the rate of immune‐related adverse events. Therefore, there has been much interest in identifying additional immune checkpoints to improve the outcomes seen with PD‐1–based therapy while minimizing additional side effects. One such target, lymphocyte‐activation gene 3 (LAG‐3), has long been recognized as an important inhibitor of T‐cell function via modulation of the T‐cell receptor pathway. Several drugs targeting LAG‐3 have been developed, including most prominently the monoclonal antibody relatlimab. To date, the most significant demonstration of efficacy in targeting LAG‐3 has been the use of relatlimab with the PD‐1 inhibitor nivolumab in the treatment of advanced melanoma. The combination of nivolumab plus relatlimab is more efficacious compared to PD‐1 inhibition alone, as has been previously seen with the combination of CTLA‐4 inhibitor ipilimumab with nivolumab. However, nivolumab plus relatlimab offers a potentially more favorable toxicity profile. Here, the authors review the mechanism of the LAG‐3 pathway and its rationale as a target for anticancer therapy as well as currently available data regarding the use of LAG‐3 agents in treating melanoma and other solid tumors. Other investigational agents that target LAG‐3 via novel mechanisms are also reviewed.

Background Allogeneic stem cell transplantation (allo‐SCT) has curative potential and was previously considered by several experts superior to autologous stem cell transplantation (auto‐SCT) for patients with multiple myeloma relapsing after first‐line auto‐SCT. Methods The authors conducted a comprehensive literature review of English‐language studies published from 1995 to October 2024. Five studies comparing allo‐SCT with second auto‐SCT following first line auto‐SCT in multiple myeloma were included. Two additional studies comparing patients with or without a suitable allo‐SCT donor after relapse were analyzed separately. Individual data from 815 patients were obtained from two large databases: the Japan Society for Hematopoietic Stem Cell Transplantation and the Center for International Blood & Marrow Transplant Research (CIBMTR). Data from five smaller studies (three comparing allo‐vs. auto‐SCT and two comparing donor vs. no‐donor groups) presented via Kaplan–Meier curves were digitized using the Shiny app. Meta‐analyses were performed using R 4.3.3. Kaplan–Meier and log‐rank tests for overall survival (OS) and progression‐free survival (PFS) were conducted in SPSS. Results Individual patient data analysis showed significantly longer OS in the auto‐SCT group. This benefit was consistent in the three smaller studies. PFS was also superior for auto‐SCT in the CIBMTR data set and the pooled smaller studies. In the two‐donor vs. no‐donor studies, the donor group showed better PFS, with OS also improved when data were combined. Conclusions Allo‐SCT after relapse from first line auto‐SCT resulted in inferior OS and PFS compared to a second auto‐SCT. These findings indicate that allo‐SCT should no longer be recommended in patients with multiple myeloma relapsing after first line auto‐SCT.

Lung cancer remains a significant global health challenge, demanding innovative treatment strategies. Immune checkpoint blockade has revolutionized cancer care, leading to improved survival across advanced malignancies and has now become a standard therapy for earlier stage, resectable lung cancer. This review article consolidates the current landscape and future prospects of neoadjuvant and perioperative immunotherapy in lung cancer. The authors outline key findings from clinical trials in resectable lung cancer, including early efficacy, safety profiles, and emerging impact on disease recurrence, and overall survival. Additionally, this review elucidates the challenges encountered, including patient selection criteria, optimal treatment schedules, immune‐related adverse events, and impact on surgery. This comprehensive analysis amalgamates current evidence with future directions, providing a roadmap for clinicians, researchers, and stakeholders to navigate the dynamic realm of immunotherapy for surgically resectable lung cancer.

Purpose Improvements in systemic therapy have resulted in significant heterogeneity in survival outcomes for metastatic breast cancer patients. As such, recently proposed staging guidelines for de novo metastatic breast cancer stratify patients into four categories (IVA/IVB/IVC/IVD). Expanding on this, overall survival (OS) outcomes for patients with Stage III vs Stage IV breast cancer were compared based on the previously defined American Joint Committee on Cancer guidelines and recently proposed subgroups for de novo metastatic breast cancer. Methods Adult patients diagnosed with Stage III or IV breast cancer in the National Cancer Database (2010–2019) were stratified as IIIA/B/C (American Joint Committee on Cancer, 8th edition) or IVA/B/C/D. OS was estimated using the Kaplan‐Meier method. Cox proportional hazards models estimated the association between stage subgroups and OS. Results Among 81,128 patients (median follow‐up, 76.8 months), 83.5% were Stage III and 16.5% Stage IV. Unadjusted 3‐year OS rates were 85.7% for Stage III versus 68.3% for Stage IV. From Stage III to Stage IV, OS declined but there was notable convergence in OS between subgroups. The unadjusted 3‐year OS for IIIC was 69.6%, which was lower than IVA (87.0%) and IVB (78.4%). Adjusted analysis showed similar trends, with the HR for IIIC at 1.94, which was worse than IVA at 1.20 and IVB at 1.83 (ref: IIIA, overall p < .001). Conclusions It was demonstrated that the survival outcomes for select patients with Stage IV breast cancer have significant convergence in OS with some patients with Stage III disease. These findings may be important for patient counseling, treatment approaches, and clinical trial design.

In this issue of Cancer, Cecchini et al. report findings from a phase 2, open‐label trial of olaparib in 30 patients with advanced cholangiocarcinoma with isocitrate dehydrogenase 1 and 2 mutations. Although the trial did not meet its primary end point, a subset of patients experienced prolonged clinical benefit, which highlights the potential for alternative therapeutic strategies involving poly(adenosine diphosphate ribose) polymerase inhibitors in future clinical trials.

Background In the phase 3 EMPOWER‐Lung 1 study, first‐line cemiplimab monotherapy provided significant survival benefit versus chemotherapy in patients with advanced non–small cell lung cancer (NSCLC) with programmed cell death‐ligand 1 (PD‐L1) ≥50%. This exploratory subgroup analysis investigated the clinical outcomes of cemiplimab treatment in patients with advanced NSCLC with brain metastases. Methods Patients with advanced NSCLC were randomized (1:1) to cemiplimab 350 mg every 3 weeks or four cycles of platinum doublet chemotherapy (NCT03088540). Patients with symptomatic radiotherapy‐treated brain metastases were eligible to enroll. Of the 565 patients with confirmed PD‐L1 expression ≥50%, 69 (12%) had brain metastases at baseline. Results Patients with brain metastases who received cemiplimab had a median overall survival (OS) of 52.4 months compared with 20.7 months for those who received chemotherapy (hazard ratio [HR], 0.40; p = .0031) and a median progression‐free survival (PFS) of 12.5 versus 5.3 months (HR, 0.33; p = .0002), respectively. Patients without brain metastases had a median OS of 24.3 months with cemiplimab versus 12.5 months with chemotherapy (HR, 0.63; p < .0001); their median PFS was 6.5 months versus 5.2 months (HR, 0.55; p < .0001), respectively. Cemiplimab was associated with a significant improvement in global health status/quality of life in all patients, including those with brain metastases. The cemiplimab safety profile was generally similar in all patients. Conclusions In patients with advanced NSCLC with PD‐L1 ≥50%, first‐line cemiplimab monotherapy improved survival and patient‐reported outcomes over chemotherapy for those who received prior radiotherapy for symptomatic brain metastases.

The past decade has witnessed remarkable advances in deciphering the pathophysiology of acute lymphoblastic leukemia (ALL) and in developing novel targeted therapies. Basic research and genomic mapping have identified new prognostic biomarkers, targets, and ALL subtypes (e.g., Philadelphia‐like ALL). The ongoing therapeutic revolution in ALL is driven by the addition to the treatment arsenal of therapies that target the ABL fusions, like the BCR::ABL1 tyrosine kinase inhibitors, as well as novel agents that target CD19 and CD22: the CD22 antibody–drug conjugate inotuzumab ozogamicin, the bispecific CD3/CD19 T‐cell engager antibody blinatumomab, and CD19 chimeric antigen receptor T‐cell therapies. These combinations have improved the long‐term survival rates in B‐cell ALL to 70%, and in Philadelphia chromosome‐positive ALL to 80%–90%. The desired goals are to achieve cure rates comparable to those in pediatric ALL and to reduce or eliminate the need for prolonged intensive/maintenance chemotherapy and associated toxicities.

Significant advances have been made in the treatment of patients with gynecologic malignancies in the past few years. Integration of molecular testing in endometrial cancer now allows for more accurate risk stratification and personalized treatment recommendations for patients, with PORTEC‐4a investigating outcomes after treatment de‐escalation based on molecular subgroup. In several clinical trials, mismatch repair‐deficiency (MMR‐d) status has been proven to be a strong predictor for response to immunotherapy in the advanced/metastatic setting, and the role of immunotherapy in early‐stage endometrial cancer is now being investigated. For patients with locally advanced cervical cancer, results from INTERLACE demonstrate that induction chemotherapy is now a viable treatment option, and KEYNOTE A‐18 shows promise for the addition of concurrent and maintenance pembrolizumab to chemoradiation. Meanwhile, EMBRACE 1 and 2 have demonstrated the benefits of high‐quality image guided brachytherapy, providing patients with locally advanced cervical cancer excellent control with improved toxicity. For patients with vulvar cancer, GOG279 demonstrated that addition of multi‐agent chemotherapy with intensity modulated radiation therapy resulted in high rates of complete pathologic response, and GROINS‐V III is currently investigating the role of chemotherapy and nodal radiation for patients with macrometastases on sentinel lymph node biopsy. This work summarizes the findings of recent landmark trials in endometrial, cervical, and vulvar cancer and their implications for the radiation oncologist.

Overall, much progress was made in 2024 in the realm of neoadjuvant immunotherapy including the firm establishment of neoadjuvant immunotherapy as superior to only adjuvant immunotherapy for patients with resectable stage III melanoma with the NADINA trial results. However, unanswered questions remain regarding the optimal neoadjuvant immunotherapy regimen, long‐term outcomes after modifying adjuvant approaches based on pathologic response, and if additional measurements of antitumor efficacy, in addition to pathologic response, can further help tailor adjuvant therapy decisions.