American Journal of Clinical Oncology-Cancer Clinical Trials最新文献

Triple-negative breast cancer is characterized by high lethality attributed to factors such as chemoresistance, transcriptomic, and genomic heterogeneity, leading to a poor prognosis and limiting available targeted treatment options. While the identification of molecular targets remains pivotal for therapy involving chemo drugs, the current challenge lies in the poor response rates, low survival rates, and frequent relapses. Despite various clinical investigations exploring molecular targeted therapies in conjunction with conventional chemo treatment, the outcomes have been less than optimal. The critical need for more effective therapies underscores the urgency to discover potent novel treatments, including molecular and immune targets, as well as emerging strategies. This review provides a comprehensive analysis of conventional treatment approaches and explores emerging molecular and immune-targeted therapeutics, elucidating their mechanisms to address the existing obstacles for a more effective management of triple-negative breast cancer.

Introduction: Insurance denials for clinical trials serve as a pertinent barrier for patients to remain trial-eligible, thus hindering the development of therapies and the overall advancement of health care. We present results from an ongoing oncology randomized clinical trial regarding insurance denials and peer-to-peer authorization (P2PA) success rate in allowing patients to remain trial-eligible.

Methods: The ongoing Spine Patient Optimal Radiosurgery Treatment for Symptomatic Metastatic Neoplasms Phase II trial randomizes spine cancer patients to treatment with spine radiosurgery/stereotactic body radiation therapy (SBRT) versus conventional external beam radiation therapy (EBRT). Trial-eligible patients during the first 3 months of enrollment are examined to determine whether the option of SBRT was denied by their insurance. Advocacy for overcoming SBRT denial in P2PA centered on SBRT being recommended as a preferred treatment modality in the National Comprehensive Cancer Network guidelines, and the recent level I evidence demonstrating the advantages of SBRT over EBRT for symptomatic spine cancer.

Results: Of 15 trial-eligible patients, 3 (20%) experienced insurance denials for SBRT. P2PA resulted in the reversal of denials in all 3 patients, allowing each to remain trial-eligible for randomization between SBRT and cEBRT.

Conclusions: Despite a clinical oncologic treatment modality for which recent Level 1 evidence is available, the insurance denial rate was 20%. A vigilant P2PA strategy focusing on highlighting National Comprehensive Cancer Network guidelines and the supporting Level 1 evidence resulted in a very high rate of reversing initial denial.

Objectives: There has been a recent emphasis in the peer-reviewed oncology literature on examining disparities by gender. Such emphasis provides an excellent opportunity to simultaneously examine race/ethnicity disparities in the same cohort. The degree to which gender disparities research has been performed concomitantly with racial disparities research at prominent oncologic societies has yet to be investigated.

Methods: ABSTRACTs presented at the American Society of Clinical Oncology (ASCO) annual meeting were reviewed. Abstracts selected for the oral abstract or clinical science symposium sessions at the 2020, 2021, and 2022 annual meetings were evaluated to determine the amount of gender disparities research presented. Such research was further assessed to determine whether racial/ethnicity disparities were examined simultaneously.

Results: From 2020 to 2022, 1219 abstracts were presented at the ASCO annual meetings, oral abstract or clinical science symposium sessions. Of these, 7 involved gender disparities examination, of which only 2 (29%) concomitantly examined race/ethnicity. No study since 2020 concomitantly examined gender and racial disparities.

Conclusions: More than 70% of gender disparities work presented at ASCO has been disaggregated from concomitant racial disparities examination, with complete disaggregation since 2021. Gender disparities work remains a miniscule aspect of the overall research landscape. Future work in examining gender disparities may be best aggregated with racial/ethnicity disparities to optimize timely solutions in both areas; such work could potentially be incentivized from the inclusion criteria of future funding mechanisms.

Objectives: Pancreatic cancer is often diagnosed at advanced stages with high-case fatality. Many tumors are not surgically resectable. We aimed to identify features associated with survival in patients with surgically nonresected pancreatic cancer in the Military Health System.

Methods: We used the Military Cancer Epidemiology database to identify the Department of Defense beneficiaries aged 18 and older diagnosed with a primary pancreatic adenocarcinoma between January 1998 and December 2014 who did not receive oncologic surgery as treatment. We used Cox Proportional Hazard regression with stepwise procedures to select the sociodemographic and clinical characteristics related to 2-year overall survival, expressed as adjusted hazard ratios (aHR) and 95% CIs.

Results: Among 1148 patients with surgically nonresected pancreatic cancer, sex, race-ethnicity, marital status, and socioeconomic indicators were not selected in association with survival. A higher comorbidity count (aHR 1.30, 95% CI: 1.06-1.59 for 5 vs. 0), jaundice at diagnosis (aHR 1.57, 95% CI: 1.33-1.85 vs. no), tumor grade G3 or G4 (aHR 1.32, 95% CI: 1.05-1.67 vs. G1/G2), tumor location in pancreas tail (aHR 1.49, 95% CI: 1.22-1.83 vs. head) or body (aHR 1.30, 95% CI: 1.04-1.62 vs. head), and metastases were associated with survival. Patients receiving chemotherapy (aHR 0.66, 95% CI: 0.57-0.76) had better survival compared with no treatment.

Conclusions: In a comprehensive health system, sociodemographic characteristics were not related to survival in surgically nonresected pancreatic cancer. This implicates access to care in reducing survival disparities in advanced pancreatic cancer and emphasizes the importance of treating patients based on clinical features.

Background: Cancer cachexia is a syndrome of unintentional weight loss resulting in progressive functional impairment. Knowledge of radiation therapy utilization in patients with cancer cachexia is limited. We evaluated the use of curative and palliative-intent radiation for the management of patients with non-small cell lung cancer (NSCLC) with cachexia to determine whether tumor-directed therapy affected cachexia-associated outcomes.

Methods: Using an Institutional Tumor Registry, we evaluated all patients with stages of NSCLC treated at a tertiary care system from 2006 to 2013. We adopted the international consensus definition for cachexia, with staging designated by the registry and positron emission tomography. Radiotherapy delivery and intent were retrospectively assessed.

Results: In total, 1330 patients with NSCLC were analyzed. Curative-intent radiotherapy was utilized equally between patients with cachexia and non-cachexia with stages I to III NSCLC. Conversely, significantly more patients with stage IV disease and cachexia received palliative radiotherapy versus those without (74% vs 63%, P = 0.006). Cachexia-associated survival was unchanged irrespective of tumor-directed radiation therapy with curative or palliative intent. In fact, pretreatment cachexia was associated with reduced survival for patients with stage III NSCLC receiving curative-intent radiotherapy (median survival = 23.9 vs 15.0 mo, P = 0.009). Finally, multivariate analysis identified pretreatment cachexia as an independent variable associated with worsened survival (hazard ratio = 1.31, CI: 1.14,1.52).

Conclusion: Patients with advanced NSCLC with cachexia received more palliative-intent radiation than those without weight loss. Tumor-directed therapy in either a curative or palliative approach failed to alter cachexia patient survival across all stages of the disease. These findings offer critical information on the appropriate utilization of radiation in the management of patients with NSCLC with cachexia.

Background: Studies addressing second hematologic malignancies (SHMs) in patients with primary mediastinal germ cell tumors (PMGCTs) are scarce. To better describe this phenomenon, we analyzed a large case series from a population-based registry.

Methods: The Surveillance, Epidemiology, and End Results database was used to report the clinical characteristics and incidence of SHMs in patients with PMGCT.

Results: Among 1297 PMGCTs, 27 cases (2.08%) of SHM were found, with a median latency period of 12 months (95% CI: 5-41). All SHM occurred in males, 20 of whom (74.1%) had a previous nonseminomatous tumor. Acute myeloid leukemia was the most frequent SHM, accounting for 13 cases, 4 of which were acute megakaryoblastic leukemia that occurred within 5 months of diagnosis. The median survival after the diagnosis of SHM was 6 months (95% CI: 2-41). The risk of SHM was significantly higher than expected for the reference population, with a standardized incidence ratio of 6.21 (95% CI: 3.31-10.62) and an absolute excess risk of 19.19 per 10,000 person-years.

Conclusions: Patients with PMGCT are at a higher risk of developing SHMs than the general population, particularly acute myeloid leukemia. This risk ranges from synchronous diagnosis of acute megakaryoblastic leukemia to the later onset of other hematological disorders that might be related to PMGCT therapies. Our findings may help create follow-up schedules for patients with PMGCT and raise the level of suspicion surrounding this association.

Introduction: The role of internal mammary nodal irradiation (IMNI) as a component of regional nodal radiotherapy is a controversial issue in breast radiation oncology with conflicting results presented in recent landmark trials. We thus created a meta-analysis of available data to better ascertain the potential benefit of IMNI. We hypothesize that with the increased power available within a meta-analysis, IMNI will prove to improve overall survival (OS) in breast cancer.

Methods: Literature search was conducted for prospective studies comparing IMNI to no IMNI. Primary endpoint was OS and secondary endpoints included local recurrence, regional recurrence, disease-free survival (DFS), breast cancer mortality (BCM), distant metastasis-free survival (DMFS), grade 2+ skin toxicity, cardiac events, and pneumonitis events. Subgroup analyses were performed for tumor location (medial/central vs. lateral), and nodal status (pN+ vs. pN0). Fixed-effect model was used if there was no heterogeneity, random-effects model otherwise.

Results: Four studies with a total of 5258 patients (IMNI: n=2592; control: n=2666) were included in the study. Pooled results showed IMNI significantly improved OS for all-comers (hazard ratio [HR]=0.89; 95% CI 0.81-0.97; P =0.008), as well as subgroups of pN+ with medial/central tumor location (HR=0.84; 95% CI 0.73-0.96; P =0.01) and pN+ with lateral tumor location (HR=0.87; 95% CI 0.77-0.99; P =0.04). There was no significant difference in OS for subgroups of pN0 and medial/central tumor location. There was no difference in local recurrence, but regional recurrence was significantly improved ( P =0.04). Endpoints of DFS (HR 0.91, 95% CI 0.84-0.99 P =0.03), BCM (HR 0.87, 95% CI 0.77-0.98, P =0.03), and DMFS (HR=0.87; 95% CI, 0.78-0.98; P =0.02) were all improved with IMNI. Grade 2+ skin toxicity, cardiac events and pneumonitis events were not significantly different between patient in the IMNI and no IMNI groups.

Conclusion: Inclusion of IMN irradiation improves OS, DFS, BCM, and DMFS in breast cancer. Largest effect on OS was noted in the subgroup of patients with pN+ and medial/central tumor location.

Background: Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by the absence of expression of estrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2. This subtype of breast cancer is known for its high aggressiveness, high metastatic potential, tendency for recurrence, and poor prognosis. Patients with metastatic TNBC (mTNBC) have a poorer prognosis and a higher likelihood of early death (survival time ≤3 months). Therefore, the development of effective individualized survival prediction tools, such as prediction nomograms and web-based survival calculators, is of great importance for predicting the probability of early death in patients with metastatic TNBC.

Methods: Patients diagnosed with mTNBC in the Surveillance, Epidemiology, and End Results database between 2010 and 2015 were included in the model construction. Univariate and multivariate logistic regression analysis was performed to identify risk factors associated with early death in patients with mTNBC and predictive prognostic nomograms were constructed. The accuracy of the nomograms was verified using receiver operating characteristic curves, and GiViTi Calibration belt plots were used to evaluate the model consistency. The clinical applicability of the nomograms was evaluated using decision curve analysis. On the basis of the predictive prognostic nomograms, a network survival rate calculator was developed for individualized survival prediction in patients with mTNBC.

Results: A total of 2230 patients diagnosed with mTNBC were included in the Surveillance, Epidemiology, and End Results database for this study. After strict exclusion criteria, 1428 patients were found to be eligible for the study. All the patients were randomly divided into a training cohort and a validation cohort in a ratio of 7:3. Independent risk factors for mTNBC, including age, tumor size, brain metastasis, liver metastasis, surgery, and chemotherapy, were identified and integrated to construct the prediction nomogram and survival calculator. Results of receiver operating characteristic curves, calibration curves, and decision curve analysis curves from the training and validation cohort confirmed that the developed nomogram and web-based survival calculator in this study could accurately predict the probability of early death in patients with mTNBC.

Conclusions: In this study, we developed a reliable prediction nomogram and web-based survival calculator for predicting the probability of early death in patients with mTNBC. These tools can assist clinical physicians in identifying high-risk patients and developing personalized treatment plans as early as possible.

Objectives: The coronavirus disease 2019 pandemic refocused the cancer community on bringing clinical trials closer to patients and increasing access for traditionally underserved communities. Pandemic-era deregulation increased flexibility with telemedicine visits, less frequent testing, and the ability to have tests done locally. This study evaluates the impact of 2020 cancer clinical trial reform on trial accessibility in rural/underserved regions of the Midwest.

Methods: Publicly available clinicaltrials.gov data was accessed from January 1, 2018 to September 30, 2022 for the 3 leading causes of new cancer cases in Kentucky, Tennessee, Illinois, and Indiana. Interventional trials were categorized based on location using corresponding "Rural-Urban Commuting Area" codes (urban/metropolitan, suburban/micropolitan, small town/rural, and isolated/rural) and categorized as pre versus postpandemic (using March 15, 2020, when national regulatory guidelines were modified). Locations of trial offerings from pre and postpandemic dates were analyzed by paired t test. Comparison of trial location category by state and cancer type was analyzed by 1-way analysis of variance with pairwise multiple comparisons made using the Tukey-Kramer method.

Results: Pandemic-era deregulation had no impact on increasing trial availability in suburban and small-town/rural locales ( P = 0.1259). Only 18% of trials were offered outside of urban areas, with 15% in suburban and 3% in small town/rural areas. Results varied by state ( P < 0.0001) with Illinois offering the most suburban and small-town trial availability (27%) compared with Kentucky, Indiana, and Tennessee (18%, 6%, and 2%, respectively). Trial availability in rural versus urban areas did not differ by cancer type ( P = 0.07197).

Conclusions: More work must be done to increase access to cancer clinical trials in rural and suburban areas of the United States.

Objectives: The Hispanic/Latinx population has consistently faced disparities in oncology access and outcomes with cancer being the leading cause of death in this population. We evaluate recent research in radiation therapy disparities among the Hispanic/Latinx population in the United States since our seminal analysis from 2017.

Methods: A PubMed literature search was conducted for articles published from January 2017 through March 2023. Four term combinations were utilized, including: (1) "Hispanic" and "Radiotherapy" and "Disparities", (2) "Latino" and "Radiotherapy" and "Hispanic", (3) "Hispanic" and "Radiation" and "Disparities", and (4) "Latino" and "Radiation" and "Disparities." Included studies were those taking place in the United States, examined radiation oncology care, and examined health disparities.

Results: Fifty-eight of 245 articles returned met inclusion criteria and spanned 6 disparity-types: (1) Stage at Presentation, (2) Time to Treatment Initiation & Completion, (3) Receipt of Treatment and Guideline-Concordant Care, (4) Geography, (5) Clinical Trial Access and (6) Insurance Barriers and Treatment Center Type. The most common disparity was receipt of treatment and guideline-concordant care (n=39 studies), demonstrating that the Hispanic/Latinx population was less likely to receive guideline-concordant treatment or treatment at all. In additon, studies identified disparities in time to treatment and completion (n=12), geography (n=5), clinical trial access (n=3), and insurance and treatment center access (n=5).

Conclusions: Disparities in radiotherapy access remain prominent for the Hispanic/Latinx population through a multitude of barriers, despite increasing interest in disparities research. Continued health care disparities research with tangible interventions are needed in radiation oncology to properly understand and address this problem.