Significant Difference In Overall Survival Research Articles

Efficacy of immunotherapy retreatment in patients with non-small cell lung cancer receiving consolidative durvalumab.

8625 Background: The standard of care for patients with stage III, unresectable non-small cell lung cancer (NSCLC) is curative intent chemoradiation followed by durvalumab consolidation. However, most patients progress necessitating further treatment. Although immunotherapy (IO) is the cornerstone of treatment in advanced/metastatic disease, the benefit in patients who received prior durvalumab is unclear. Clinical trials excluded prior IO exposure and current guidelines do not provide specific recommendations. This study aims to characterize the efficacy of post-durvalumab IO treatment. Methods: This was a retrospective cohort study conducted at the University of North Carolina (UNC) Medical Center. Adult patients with unresectable NSCLC who received chemoradiation and consolidative durvalumab followed by subsequent systemic therapy for disease progression between February 2018 to May 2023 were included. Patients were excluded if they received targeted therapy as subsequent systemic treatment. The primary endpoint was real-world progression-free survival (rwPFS) of post-durvalumab treatment. Key secondary outcomes included physician assessed response, overall survival (OS), and subgroup analyses to identify biomarkers which may predict benefit from IO retreatment. Results: A total of 66 patients met inclusion criteria, of which 39 (59%) received subsequent chemotherapy alone and 27 (41%) received IO-containing therapy. Of those who received IO-containing treatments, 18 received chemotherapy plus IO (chemoIO) and 9 received IO alone. Durvalumab was discontinued for therapy completion (chemotherapy: 18%, IO: 26%), disease progression (chemotherapy: 54%, IO: 48%), or side effects (chemotherapy: 26%, IO: 19%). No significant difference was observed between median rwPFS of chemotherapy versus IO-containing therapy (7.0 months vs 5.8 months, respectively; p = 0.9419) or OS (13.0 months vs 12.6 months, respectively; p = 0.5769). Notably, patients in our cohort who received IO alone had a numerically longer rwPFS compared to chemoIO (12.6 months vs 5.8 months, respectively; p = 0.3951), as well as a numerically longer OS (12.6 months vs 6.4 months, respectively; p = 0.8885). Conclusions: This study found that there were no statistically significant differences in median rwPFS or OS between chemotherapy or IO-based regimens following the conclusion of durvalumab consolidation. Interestingly, we observed a numerically improved rwPFS and OS in those who received IO alone compared to chemoIO, which suggests there may be key clinical or molecular features that may help identify patients who benefit from IO therapy. We acknowledge the limitations of this small, retrospective study. The efficacy of IO-based regimens post-durvalumab warrants further investigation in a larger, prospective manner to assess the risks and benefits of IO retreatment.

A retrospective study of PD-1/PD-L1 combination therapy versus TKI monotherapy in elderly patients with uHCC.

e16191 Background: The rising elderly population worldwide has led to an increase in cases of liver cancer among individuals aged ≥65 years. With the advancement of medical treatments, the management of unresectable hepatocellular carcinoma (uHCC) now predominantly involves immunotherapy combination therapy. However, existing data in elderly patients are limited. Therefore, we conducted a retrospective analysis on the efficacy and safety of immune combination therapy compared with TKI monotherapy in elderly uHCC patients. Methods: A retrospective analysis was conducted on uHCC patients aged ≥65 years at the First Hospital of Jilin University between March 2019 and July 2023. The targeted therapy used in this study included, but not limited to, sorafenib, lenvatinib. PD-1/PD-L1 inhibitors such as pembrolizumab and atezolizumab were also utilized. Follow-up was conducted until death, loss to follow-up, or December 2023. The primary endpoint was overall survival (OS), while the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), adverse events (AEs) and immune-related AEs (irAEs). Results: A total of 70 patients were included in this study, with 33 patients receiving monotherapy, and 37 patients receiving immune combination therapy. The median age was 68 years old, with 78.8% being male. The combination therapy group had a higher ORR (10.8% vs. 3.0%) DCR (48.5% vs. 45.9%) compared to the monotherapy group. However, there were no statistically significant differences in median PFS (7.0 vs. 12.0 months) and median OS (9.8 vs. 17.5 months) between the two groups. Among the subgroups, combination therapy showed better results except for patients with ascites. Immune combination therapy appeared to be superior to monotherapy in terms of both PFS (6.2 vs. 6.8 months, P = 0.888) and OS (6.8 vs. 10.2 months, P = 0.888). Multivariate analysis showed that elevated total bilirubin may be a risk factor for OS in patients ≥65 years old. Regarding safety, the adverse event (AE) rate was 39.3% in the monotherapy group. The most common AEs reported were abdominal distension (18.2%), fatigue (15.2%), and proteinuria (6.1%). In the combination therapy group, the AE rate was higher at 59.4%, with the most common AEs being thyroid function abnormalities (24.3%), fatigue(24.3%), decreased appetite(18.9%), and hypertension(18.9%). The rate of drug withdrawal due to adverse reactions was significantly higher in patients receiving combination therapy compared to those receiving monotherapy (40.5% vs. 12.1%, P = 0.008). Conclusions: In elderly uHCC patients (≥65 years old), immune combination therapy shows a higher ORR and potentially longer PFS and OS except patients with ascites. AEs and drug withdrawal rates are higher in the combination therapy group. Further discussions are needed to determine the optimal treatment strategy for elderly uHCC patients.

Start low, go slow: A systematic review and meta-analysis of upfront tailored treatment dosing in older adults with advanced cancer.

1625 Background: Older adults aged ≥65 with advanced cancer are underrepresented in treatment trials. This gap limits informed decision-making regarding the dose and tolerability of proposed therapies. Standard chemotherapy is associated with >50% serious adverse event rate among older adults, with frequent dose reduction and early treatment discontinuation. A "start low, go slow" (SLGS) approach begins systemic therapy at lower-than-standard doses and increases the dose if well-tolerated. This alternative dosing strategy has shown value in minimizing adverse events and functional decline without compromising the overall effectiveness of treatments. We conducted the first systematic review and meta-analysis of SLGS effectiveness among older adults across advanced cancers. Methods: This review, was registered with PROSPERO and adhered to PRISMA criteria, covering PubMed, Journal of Geriatric Oncology and EMBASE from January 2000 until December 15, 2024. Eligible study designs were randomized controlled trials, retrospective trials, and non-randomized clinical trials with patients with advanced cancers who underwent systemic therapy. We reported all studies that studied the SLGS approach. Our studied outcomes were overall survival (OS), progression-free survival (PFS), treatment discontinuation, and toxicity. Data extraction included author, patient, cancer type, treatment, and survival outcomes. A meta-analysis using fixed effects and risk ratios (RR) was performed when sufficient data was available; significant outcomes had α<0.05. Results: Our search identified 13 studies testing SLGS strategies in oncology, including 3,508 patients, with a median age 63-78 years. The -represented cancers included colorectal (6 studies, 3059 patients total), lung (2 studies, 113 pts), chronic myeloid leukemia (2 studies, 127 pts), non-Hodgkin lymphoma (1 study, 45 pts), and prostate (2 studies, 164 pts) cancers. Ten (77%) studies assessed OS and PFS. Five studies (39%) compared SLGS against standard doses, finding no significant differences in PFS and OS across all trials. Dose escalation rates for SLGS ranged from 5% to 60%. The ability to complete planned cycles was higher with SLGS compared to standard dose (1 study, 43% vs 26%, p=0.04). Treatment discontinuation was not different for SLGL vs. standard dose (5 studies, meta-analysis RR 1.07, 95% CI 0.90-1.27, p=0.42). Toxicity ranged from 5% to 89% across studies; SLGS had lower grade ≥3 adverse events compared to standard dose (4 studies, meta-analysis RR 0.88, 95% CI 0.80-0.94, p < 0.001). Conclusions: This is the first systematic review and meta-analysis analyzing the SLGS approach to systemic therapy dosing in older adults with advanced cancer. Compared to standard-dose systemic therapy, older adults pursuing a SLGS strategy had greater completion of planned cycles, reduced toxicity, and similar survival.

SU2C-SARC032: A randomized trial of neoadjuvant RT and surgery with or without pembrolizumab for soft tissue sarcoma.

11504 Background: Surgery & radiation therapy (RT) yield high local control rates for soft tissue sarcoma (STS) of the extremity and limb girdle. However, patients (pts) with high-grade stage III STS are at significant risk for developing metastasis. Median survival for pts with metastatic STS is < 2 years. SARC028 (NCT02301039) evaluated the efficacy of pembrolizumab (pembro) for metastatic STS, showing 20% and 8.7% response rates in undifferentiated pleomorphic sarcoma (UPS) and pleomorphic/dedifferentiated liposarcoma (LPS), respectively. We hypothesized that neoadjuvant pembro with concurrent RT followed by surgery and adjuvant pembro for stage III UPS, including myxofibrosarcoma, or LPS would stimulate an anti-tumor immune response to eliminate micrometastatic disease & improve disease-free survival (DFS). SU2C-SARC032 (NCT03092323) is a multi-institutional, international, randomized phase 2 trial evaluating the safety and efficacy of adding pembro to standard of care (SOC) RT & surgery for pts with stage III UPS or LPS. Methods: Pts aged > 12 yo with stage III (FNCLCC grade 2 or 3) UPS or LPS of the extremity and limb girdle were enrolled. Pts were randomized (1:1, stratified by grade) to neoadjuvant RT (50 Gy/25 fx) then surgery (SOC arm) or neoadjuvant pembro and RT then surgery & adjuvant pembro (EXP arm). Pembro was given 200 mg IV Q3 wk for 3 doses (before, during & after RT) & up to 14 adjuvant cycles. The primary endpoint was 2-yr DFS. Secondary endpoints included local recurrence-free survival (LRFS), distant disease-free survival (DDFS), & overall survival (OS). Target enrollment of 126 evaluable patients (max 144 total) provided 80% power (1-sided α = 0.05) to distinguish between a null hypothesis of 50% 2-yr DFS rate & alternative hypothesis of 75% 2-yr DFS rate by log-rank test, with initial analysis at 45 DFS events. Cox models were stratified by grade; primary analysis was a one-sided stratified log-rank test. Results: Between July 2017-November 2023, 143 patients were enrolled, predominantly with UPS (85%) & grade 3 (64%) histology. Median follow-up for alive patients is 24.1 mo. DFS in the EXP arm is significantly higher than the SOC arm (p = 0.023; HR 0.57, 90% CI: 0.35, 0.91). Estimated 2-yr DFS is 53% (90% CI: 43, 66%) for SOC vs 70% (90% CI: 61, 81%) for EXP arm. Currently, there is no statistically significant difference in LRFS (HR 0.55, 95% CI: 0.21, 1.42), DDFS (HR 0.57, 95% CI: 0.32, 1.01), or OS (HR 0.39, 95% CI: 0.14, 1.12). Pts with grade 3 sarcomas had improved DFS with pembro (HR 0.47, 95% CI: 0.25, 0.89), but no difference in DFS was observed in grade 2 tumors (HR 1.21, 95% CI: 0.35, 4.18). The proportion of patients with grade 3+ adverse events was significantly higher in EXP (52%) vs SOC arm (26%) (p = 0.002). Conclusions: Theaddition of neoadjuvant & adjuvant pembro to RT and surgery significantly improves DFS for pts with stage III UPS and LPS of the extremity and limb girdle. Clinical trial information: NCT03092323 .

Long-term follow up of E3311, a phase II trial of transoral surgery (TOS) followed by pathology-based adjuvant treatment in HPV-associated (HPV+) oropharynx cancer (OPC): A trial of the ECOG-ACRIN Cancer Research Group.

6009 Background: E3311 is a phase II trial of TOS by credentialed surgeons with pathology-driven deintensified post-operative management in HPV+ OPC. Intermediate risk patients were randomized between standard and reduced dose radiation. We present mature outcome data, at median follow up of 52.4 months (m). Methods: Patients were eligible who had resectable cT1-2 stage III/IV AJCC7 p16+ OPC without matted neck nodes. Those with clear margins, 0-1 + nodes (LN), and no extranodal extension (ENE) were observed (Arm A, N=38); those with clear margins, 2-4 + LN, or ENE ≤1mm were randomized to 50Gy (Arm B, N=100) or 60Gy (Arm C, N=108); those with involved margins, >4 + LN, or >1mm ENE received weekly cisplatin 40 mg/m2 and 60-66Gy (Arm D, N=113). Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared using a log-rank test, stratified by arm for comparisons of primary site and smoking history. Results: Among 359 evaluable patients, 54-m PFS and OS were 90.6% (90% CI: 87.2%, 93.1%) and 95.3% (90% CI: 93.0%, 96.9%). 54-m PFS by arm was: A 93.2% (90% CI: 79.6%, 97.8%); B 94.9% (90% CI: 89.7%, 97.5%); C 90.2% (90% CI: 82.7%, 94.6%) and D 85.5% (90% CI: 77.5%, 90.8%). 54-m OS by arm was: A 97.1% (90% CI: 85.7%, 99.4%); B 97.9% (90% CI: 93.5%, 99.3%), C 95.1% (90% CI: 90.1%, 97.6%) and D 92.5% (90% CI: 86.9%, 95.7%). Among patients in Arm A, 11 had N0 and 27 N1 stage. Median Arm A lymph node yield (LNY) was 29 (11 to 91 LN) and did not differ for patients with/without recurrence (p=0.83). All Arm A recurrences were in N1 patients: 1 at 18 m and 3 at > 40 m. No significant difference in PFS or OS was observed by prescribed radiation dose for intermediate risk patients (Arm B vs. C). Outcome did not differ by primary site of tonsil vs. other OPC (oOPC): 54-m PFS Tonsil 89.3% (90% CI: 84.9%, 92.5%) vs. oOPC 92.9% (90% CI: 87.0%, 96.2%), p=0.28, and 54-m OS Tonsil 94.6% (90% CI: 91.5%, 96.6%) vs oOPC 96.6% (90% CI: 92.4%, 98.5%), p=0.35. Smoking history also did not impact outcome. 54-m PFS was 89.9% (90% CI: 85.9%, 92.9%) for those with ≤10 pack-years (PY) tobacco exposure and 91.7% (90% CI: 83.9%, 95.9%) for those with >10 PY. Conclusions: TOS, neck dissection with deintensified risk-based post-operative management results in outstanding 54-m PFS and OS across all subsites of T1-2 p16+ OPC, irrespective of smoking history. Late recurrence is not increased when post-operative radiation is reduced from 60 to 50Gy for intermediate risk patients. Pathologic >1mm ENE (N=87), involved margin (N=12) or >4 involved LN (N=30) accurately identify patients at increased recurrence risk and outcomes were favorable among such patients. Among patients with favorable pathologic characteristics, a subset with N1 disease are at risk for late recurrence and further characterization of these patients is warranted. Clinical trial information: NCT01898494 .

Comparing the efficacy and safety of TACE combined with donafenib or lenvatinib in the treatment of unresectable hepatocellular carcinoma.

e16153 Background: For unresectable Intermediate/Advanced-Stage Hepatocellular Carcinoma (uHCC), the efficacy of TACE monotherapy has been unsatisfactory. Studies have shown that TACE combined with molecular targeted drugs exhibits potential synergistic effects, which can prolong the overall survival (OS) of uHCC patients (pts). Donafenib and lenvatinib are small molecule targeted drugs approved as first-line treatments for HCC. The aim of this study is to evaluate the efficacy and safety of TACE combined with donafenib or lenvatinib in the treatment of uHCC. Methods: A retrospective analysis was conducted on the clinical data of uHCC pts treated with donafenib combined with TACE (Dona-TACE) or lenvatinib combined with TACE (Lenva-TACE) at The First Affiliated Hospital of USTC from January 2018 to October 2022. The OS, progression free survival (PFS), objective response rate (ORR), and disease control rate (DCR) of two groups of pts were evaluated according to the mRECIST, and the incidence of adverse events (AEs) was evaluated using CTCAE 5.0. Pts with complete baseline information and at least one follow-up evaluation were incorporated in the final analysis. Results: A total of 105 pts treated with donafenib and 59 pts treated with lenvatinib met the study criteria. After matching with a 1:1 propensity score, 35 pts in the Dona-TACE group and 35 pts in the Lenva-TACE group were included in this study. The baseline characteristics of the two groups are similar (males, 85.7% vs. 85.7%; ECOG PS of 1, 74.3% vs. 71.4%; Exceeding up-to-seven criteria, 74.3% vs. 62.9%; BCLC stage C, 42.9% vs. 40.0%; Combination immunotherapy, 62.9% vs. 54.3%). There was no significant difference in median OS (29.0 vs. 27.3m, P = 0.748) and median PFS (10.5 vs. 10.3m, P = 0.869) in the Dona-TACE and Lenva-TACE groups. The ORR (85.7% vs. 74.3%, P = 0.969) and DCR (94.3% vs. 97.1%, P = 0.280) of the Dona-TACE and Lenva-TACE group were equivalent. Compared with the Lenva-TACE group, pts in the Dona-TACE group had a lower incidence of grade 3-4 adverse events (any grade, 94.3% vs. 91.4%; grade 3 or 4, 34.3% vs. 57.1%, P < 0.05). Among them, pts in the Dona-TACE group had a lower incidence of proteinuria (any grade, 22.9% vs 42.9%; grade 3 or 4, 0 vs17.1%, P < 0.05) and hypertension (any grade, 42.9% vs 71.4%; grade 3 or 4, 2.9% vs 25.7%, P < 0.05) than those in the Lenva-TACE group. Multivariate analysis showed that ECOG PS score, up-to-seven criteria, and tumor blood supply were independent prognostic factors affecting OS (HR, 3.470, 3.619, 3.067; P < 0.05). Conclusions: The efficacy of donafenib and lenvatinib combined with TACE in the treatment of uHCC is equivalent. Furthermore, compared to lenvatinib combined with TACE, donafenib combined with TACE has higher safety.

Clinicopathological features and prognosis for pregnancy-associated breast cancer: A matched case-control study.

e12573 Background: Pregnancy-Associated Breast Cancer (PABC) is defined as breast cancer diagnosed during pregnancy or within 1 year postpartum. Studies indicate that PABC tends to have poorer prognostic characteristics and often worse outcomes compared to non-PABC. The primary goal of this study is to examine disease characteristics associated with PABC versus non-PABC in the United Arab Emirates (UAE), where breast cancer is characterized by a younger age and more advanced stage compared to North America and Europe. Additionally, the UAE has a younger mean age for first-time mothers and a similar age for all mothers compared to North America and Europe. Methods: Patients with PABC were selected from BC cases of women ≤40 years treated at Tawam Hospital, the largest tertiary cancer center in the UAE between January 2003 – December 2020. Each PABC patient was matched to two non-PABC patients (controls) according to cancer stage, age, and year of diagnosis. The Fisher's exact and Kruskal-Wallis tests were used to compare both study groups. Results: 66 women with PABC were identified, with a median age at diagnosis of 33.0 (interquartile range [IQR]: 30.0-37.0) years. Most presented with stage II (45.5%) or stage III (39.4%) disease and underwent mastectomy and axillary lymph node dissection. Invasive ductal carcinoma was the most frequent histological type in both groups (86.4% for PABC and 85.6% for non-PABC). PABC was associated with higher grade 3 disease compared with non- PABC (53% vs 51.5% p= 0.009). More women with PABC received neoadjuvant chemotherapy (NACT) and radiation therapy (RT) compared with non-PABC (48.5% vs 3%, p <0.001 and 80.3% vs 65.9%, p= 0.046, respectively). There were no statistically significant differences with regards to tumor size, nodal involvement, underlying histologic subtype, ER/PR expression or HER-2 status, rates of breast-conserving surgery and adjuvant chemotherapy receipt between the two groups. The median progression-free survival (PFS) was 3.2 years (IQR: 1.9-7.1) in PABC and 3.4 years (IQR: 1.2-6.2) in non-PABC group (P=0.306). The median overall survival (OS) was 4.5 years in the PABC (IQR: 2.4-7.9) versus 4.5 years (IQR: 1.9-7.9) in the non-PABC group (P = 0.786). Conclusions: PABC in women ≤40 years appears to be associated with grade III tumors and NACT and RT receipt compared to non-PABC. However, there were no significant difference in PSF and OS between PABC and non-PABC. Further analysis is underway to evaluate the prognostic factors and their effect on survival.

Target trial emulation with real-world data to determine the population-level cost-effectiveness of multi-gene panel sequencing in advanced melanoma.

e21508 Background: Compared to single-gene BRAF testing to guide targeted treatment for advanced melanoma, multi-gene panels can identify additional gene mutations with known therapeutic or prognostic relevance. No randomized control trials of multi-gene panel sequencing have been completed in advanced melanoma. This study determined the population-level cost-effectiveness of multi-gene panel sequencing compared to single-gene BRAF testing for advanced melanoma. Methods: Our population-based retrospective study emulated a hypothetical pragmatic trial using comprehensive patient-level clinical and health administrative data between September 2016 and December 2018 from British Columbia, Canada. To emulate random treatment assignment, we 1:1 matched multi-gene panel patients to contemporaneous controls using a machine learning approach that maximized balance on 15 covariates. Following matching, we estimated mean three-year survival time and costs (2021 CAD), and calculated incremental net monetary benefit (INMB) for life-years gained (LYG) at $100,000/LYG using inverse probability of censoring weighted linear regression and nonparametric bootstrapping. Besides an intention-to-treat (ITT) effect, we also estimated the per-protocol (PP) effect of initiating treatment within 90 days of receiving test results additionally using inverse probability of treatment weights. We also estimated overall survival using Weibull regression and Kaplan-Meier (KM) survival analysis. Results: We matched 147 patients receiving multi-gene panel sequencing to controls, achieving good balance for all included covariates. ITT mean incremental costs were $19,541 (95%CI: -$18,939, $77,396) and mean incremental LYG were 0.22 (95%CI: -0.06, 0.50). We did not find statistically significant different differences in overall survival using the KM (P = 0.11) and Weibull regression (HR: 0.73 [95%CI: 0.51-1.03]) survival analysis in the ITT analysis. PP incremental costs were $36,367 (95%CI: -$6,653, $120,216) and incremental LYG were 0.56 (95%CI: 0.39, 1.24), with corresponding differences in overall survival using KM (P = 0.02) and Weibull regression (HR: 0.56 [95%CI: 0.36-0.87]) survival analysis. The probability of multi-gene panel sequencing being cost-effective at $100,000/LYG was 54.9% in the ITT analysis and 64.5% in the PP analysis. Conclusions: We found the cost-effectiveness of multi-gene panel sequencing to be evenly poised, with estimates favouring multi-gene panel sequencing with respect to overall survival and cost-effectiveness when accounting for probability of treatment initiation. This real-world evidence generated using randomized trial design principles can support jurisdictions’ deliberations on the reimbursement of precision oncology interventions.

Clinical features of breast cancer in Ashkenazi Jewish carriers of the two founder BRCA1 pathogenic variants.

e12557 Background: Germline pathogenic variants (PVs) in BRCA1 and BRCA2 are the most common cause of hereditary breast and ovarian cancer. Carriers have a significantly elevated risk of developing breast cancer (BC) and ovarian cancer (OC) compared to the general female population. Two prevalent PVs in Ashkenazi Jews (AJ) in the BRCA1 gene are 185delAG and 5382insC. This study aims to compare clinical features of disease between the PV carrier groups. Methods: Data was collected retrospectively on 282 BC patients who were carriers of 5382insC or 185delAG, treated in Hadassah and Shaare Zedek Medical Centers between the years 1978 and 2021. Data collected included features such as age at disease onset, staging at diagnosis, additional malignancies or recurrence of disease, pathological features such as hormone receptor status and HER2 status (tumor subtype), and treatments. Disease characteristics and outcomes were compared. Results: There were 207 carriers of the 185delAG PV, while 75 carried the 5382insC PV. Amongst carriers of 185delAG, vs. 5382InsC, 58.1% vs. 35.8% (p<0.01) had triple negative BC (TNBC), while 28.2% vs. 52.6% (p<0.01) had hormone positive BC, respectively (Table). There was no significant difference in disease-free or overall survival, even after adjusting for age, stage and other potential confounders. Although it appeared that 5382insC carriers suffered a higher rate of OC (14% vs. 9.6%), and that 185delAG had a higher rate of non-OC malignancies (8.2% vs. 4%), these differences did not reach statistical significance. Conclusions: Our study suggests that 5382insC and 185delAG differ in their patterns of disease. Despite the lower rates of TNBC, 5382insC carriers had similar survival to 185delAG carriers. This could suggest that the hormone receptor positive disease amongst 5382InsC carriers had a less favorable course of disease, with a similar outcome as in those with TNBC. Further studies are warranted to better understand this pattern of disease aggression. [Table: see text]

Robot-assisted Partial Nephrectomy for Hilar and Nonhilar Renal Masses: Comparison of Perioperative, Oncological, and Functional Results in a Multicentre Prospective Cohort (NEPRAH Study, UroCCR 175)

Background and objectiveA hilar location for a renal tumour is sometimes viewed as a limiting factor for safe partial nephrectomy. Our aim was to evaluate perioperative, oncological, and functional outcomes of robot-assisted partial nephrectomy (RAPN) for hilar tumours (RAPN-H) in comparison to RAPN for nonhilar tumours (RAPN-NH). MethodsWe conducted an observational, multicentre cohort study using prospectively collected data from the French Research Network on Kidney Cancer (UroCCR). The registry includes data for 3551 patients who underwent RAPN for localised or locally advanced renal masses between 2010 and 2023 in 29 hospitals in France. We studied the impact of a hilar location on surgery, postoperative renal function, tumour characteristics, and survival. We also compared rates of trifecta achievement (warm ischaemia time [WIT] <25 min, negative surgical margins, and no perioperative complications) between the groups. Finally, we performed a subgroup analysis of RAPN without vascular clamping. Variables were compared in univariable analysis and using multivariable linear, logistic, and Cox proportional-hazards models adjusted for relevant patient and tumour covariates. Key findings and limitationsThe analytical population included 3451 patients, of whom 2773 underwent RAPN-NH and 678 underwent RAPN-H. Longer WIT (β = 2.4 min; p < 0.01), longer operative time (β = 11.4 min; p < 0.01) and a higher risk of postoperative complications (odds ratio 1.33; p = 0.05) were observed in the hilar group. Blood loss, the perioperative transfusion rate, postoperative changes in the estimated glomerular filtration rate, and trifecta achievement rates were comparable between the groups (p > 0.05). At mean follow-up of 31.9 mo, there was no significant difference in recurrence-free survival (hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.58–1.2; p = 0.3), cancer-specific survival (HR 1.1, 95% CI 0.48–2.6; p = 0.79), or overall survival (HR 0.89, 95% CI 0.52–1.53; p = 0.69). Conclusions and clinical implicationsPatient and tumour characteristics rather than just hilar location should be the main determinants of the optimal surgical strategy for hilar tumours. Patient summaryWe found that kidney tumours located close to major kidney blood vessels led to a longer operation and a higher risk of complications during robot-assisted surgery to remove the tumour. However, tumours in these locations were not related to a higher risk of kidney function loss, cancer recurrence, or death.

Comparison of outcomes of abdominoperineal resection vs low anterior resection in very-low rectal cancer

BackgroundThe management of very-low rectal cancer is one of the most challenging issues faced by general and colorectal surgeons. Many feel compelled to pursue abdominoperineal resection (APR) over low anterior resection (LAR) to optimize oncologic outcomes. This study aimed to determine differences in long-term oncologic outcomes between patients undergoing APR or LAR for very-low rectal cancer. MethodsThe United States Rectal Cancer Consortium (2010–2016) was queried for adults who underwent either APR or LAR for stage I-III rectal cancers < 5 cm from anorectal junction and met inclusion criteria. The primary outcome was disease-free survival. Secondary outcomes included overall survival, length of stay, complications, recurrence location, and perioperative factors. ResultsA total of 431 patients with very-low rectal cancer who underwent APR or LAR were identified; 154 (35.7%) underwent APR. The overall recurrence rate was 19.6%. The median follow-up was 42.5 months. An analysis adjusted for demographics and pathologic stage observed no difference in disease-free survival between operative types (APR-hazard ratio [HR] = 0.90, 95% CI: 0.53–1.52, P = .70). Secondary outcomes demonstrated no significant difference between operation types, including overall survival (HR = 1.29, 95% CI: 0.71–2.32, P = .39), complications (OR = 1.53, 95% CI: 0.94–2.50, P = .12), or length of stay (estimate: 0.04, SE = 0.25, P = .54). ConclusionWe observed no significant difference in disease-free survival or overall survival between patients undergoing APR or LAR for very-low rectal cancer. This analysis supports the treatment of very-low rectal cancer, without sphincter involvement, by either APR or LAR.

Effect of HER2-low expression on the efficacy of CDK4/6 inhibitors in breast cancer: A meta-analysis.

e13034 Background: The effect of human epidermal growth factor receptor 2 (HER2)-low expression on the efficacy of CDK4/6 inhibitors in breast cancer is unclear. Therefore, the aim of this meta-analysis was to determine the effect of HER2-low on the efficacy of CDK4/6 inhibitors in advanced breast cancer. Methods: We searched 10 databases and meeting minutes up to July 15, 2023, to identify studies that reported median progression-free survival (mPFS) and overall survival (OS) among HR+/HER2-low breast cancer patients and HER2-zero breast cancer patients receiving treatment with CDK4/6 inhibitors. We calculated pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Results: A total of 9 retrospective studies involving 1494 patients were included. HER2-low breast cancer patients accounted for 52.48% of the sample, and HER2-zero breast cancer patients accounted for 47.52% of the sample. The mPFS was significantly worse for HR+/HER2-low breast cancer patients treated with CDK4/6 inhibitors combined with endocrine therapy than for HER2-zero breast cancer patients (risk ratio = 1.29, 95% CI: 1.15-1.44, p &lt; 0.00001). There was no significant difference in the median overall survival (mOS) between patients with HER2-low breast cancer and patients with HER2-zero breast cancer (risk ratio = 1.07, 95% CI: 0.69-1.66%, p = 0.78). The mPFS was significantly worse for HR+/HER2-low breast cancer patients receiving first-line treatment with CDK4/6 inhibitors combined with endocrine therapy (risk ratio = 1.25, 95% CI: 1.07-1.47, p = 0.0002). Conclusions: The mPFS of patients with advanced HER2-low breast cancer and first-line salvage patients receiving CDK4/6 inhibitors combined with endocrine therapy was significantly inferior to that observed in HER2-zero breast cancer patients. However, there were no discernible differences in the mOS between the two patient groups.

Association Between Preoperative Osteopenia and Prognosis in Breast Cancer Patients.

Osteopenia, the loss of bone mineral density (BMD), was recently reported as a prognostic factor in various cancers. However, the prognostic significance of preoperative osteopenia in breast cancer remains unclear. This study aimed to clarify the clinical significance of preoperative osteopenia in breast cancer. We retrospectively analyzed the relationship between osteopenia and clinical factors and prognosis in 532 patients with pathological Stage I-III primary breast cancer between 2009 and 2017. Osteopenia was assessed by measuring the average pixel density (Hounsfield unit) in the midvertebral core of the 11th thoracic vertebra on enhanced preoperative computed tomography. Osteopenia was diagnosed in 186 (35.0%) patients. The recurrence-free survival (RFS) rate was significantly worse in the osteopenia group than in the non-osteopenia group (p=0.0275), but there was no significant difference in overall survival (OS) between the two groups. When evaluated by menopausal status, RFS and OS were significantly worse in the osteopenia group than in the non-osteopenia group (p=0.0094 and p=0.0264, respectively) in premenopausal patients. However, there were no significant differences in RFS and OS between the two groups among postmenopausal patients. In premenopausal patients, osteopenia was an independent prognostic factor for RFS in a multivariate analysis (p=0.0266). Preoperative osteopenia was independently associated with recurrence of breast cancer.

Is neoadjuvant chemotherapy necessary for T2N0-1M0 hormone receptor-positive/HER2-negative breast cancer patients undergoing breast-conserving surgery?

IntroductionFor HR-positive/HER2-negative patients who can undergo breast-conserving surgery (BCS) but have a tumor size of 2–5 cm or 1–3 lymph node metastases, neoadjuvant chemotherapy (NAC) is still controversial.MethodsPatients with T2N0-1M0 HR-positive/HER2-negative BC who underwent BCS between 2010 and 2017 were selected from the SEER database. Propensity score matching (PSM) was used to minimize the influence of confounding factors. The overall survival (OS) and breast cancer-specific survival (BCSS) of patients were estimated by Kaplan‒Meier curves and Cox proportional hazard models. Independent prognostic factors were included to construct a nomogram prediction model.ResultsA total of 6475 BC patients were enrolled, of whom 553 received NAC and 5922 received adjuvant chemotherapy (AC). In the T2N0-1M0 population and T2N1M0 subgroup, AC patients before PSM had better OS and BCSS than NAC patients. After PSM, there was no significant difference in OS or BCSS between the two groups. However, in the T2N0M0 subgroup, there was no difference in survival between the AC and NAC groups before and after PSM. Stratified analysis revealed that for complete response (CR) patients, survival was roughly equivalent between the NAC and AC groups. However, the survival of no response (NR) and partial response (PR) patients was significantly worse than that of AC patients. Cox analysis revealed that radiotherapy after BCS was an independent protective factor for OS. NAC is an independent risk factor for NR and PR patients. The nomogram has good prediction efficiency.ConclusionNAC before BCS is not necessary for T2N0-1M0 HR-positive/HER2-negative BC patients.

The role of adjuvant radiotherapy for intracranial malignant meningiomas: analysis of a nationwide database.

This study aimed to examine the effect of postoperative radiotherapy on survival outcomes in patients with malignant meningiomas. We identified patients with malignant meningioma diagnosed between 2007 and 2018 using the Taiwan Cancer Registry and followed them up using the death registry. Survival was compared between patients with and without adjuvant radiotherapy. The potential confounding factors evaluated in this study included age, sex, comorbidities, and the Charlson Comorbidity Index (CCI). The analysis included 204 patients; 94 (46%) received adjuvant radiotherapy. The two groups had similar sex distributions (p = 0.53), mean age (p = 0.33), histologic subtype (p = 0.13), and CCI (p = 0.62). The prognosis of malignant meningioma was poor, with a median overall survival (OS) of 2.4 years. The median OS was 3.0 years (interquartile range (IQR) [1.4-6.1], and 2.0 years (IQR [0.5-3.9]) in the radiotherapy and non-radiotherapy groups, respectively (p = 0.001). However, Kaplan-Meier curves with the log-rank test showed no significant difference in OS between the two groups (p = 0.999). Controlling for age group, sex, histologic subtype, treatment, comorbidities, and CCI, adjuvant radiotherapy did not impart a survival benefit (hazard ratio [HR] = 0.87; 95% confidence interval [CI]: 0.6‒1.26); however, only factor of higher comorbidity score (HR = 2.03, 95%CI: 1.04‒3.94) was associated with unfavorable survival. This population-based retrospective analysis suggests that the role of radiotherapy remains unclear and underscores the need for randomized clinical trials to assess the usefulness of adjuvant radiotherapy in malignant meningioma.

Survival benefit of postoperative radioiodine therapy among patients with intermediate-risk differentiated thyroid carcinoma.

The 2015 American Thyroid Association (ATA) guidelines proposed the use of the ATA Risk Stratification System and American Joint Committee on Cancer Tumor-Node-Metastasis (AJCC/TNM) Staging System for postoperative radioiodine decision-making. However, the management of patients with intermediate-risk differentiated thyroid carcinoma (DTC) is not well defined. In this study, we aimed to evaluate the therapeutic efficacy of radioactive iodine therapy (RAIT) among various subgroups of patients with intermediate-risk DTC after surgery. This was a retrospective study based on the Surveillance, Epidemiology, and End Results (SEER) database (2010-2015). The DTC patients with intermediate risk of recurrence were divided into two groups (treated or not treated with radioactive iodine (RAI)). As the treatment was not randomly assigned, stabilized inverse probability treatment weighting (sIPTW) was used to reduce selection bias. We used the Kaplan-Meier method and log-rank test to analyze overall survival (OS) and cancer-specific survival (CSS). Kaplan-Meier analysis after sIPTW found a significant difference in OS and CSS between no RAIT and RAIT (log-rank test, P < 0.0001; P = 0.0019, respectively). The Kaplan-Meier curves of CSS in age cutoff of 55 years showed a significant association between no RAIT and RAIT (log-rank test, P = 0.0045). Univariate and multivariate Cox regression showed RAIT was associated with a reduced risk of mortality compared with no RAIT (hazard ratio [HR] 0.59, 95% confidence interval [95% CI 0.44-0.80]). Age (≥ 55) years showed a worse CSS regardless of whether or not a patient was treated or not treated with RAI ([HR] 8.91, 95% confidence interval [95% CI 6.19-12.84]). RAIT improves OS and CSS in patients with intermediate-risk DTC after surgery. 55 years is a more appropriate prognostic age cutoff for the relevant classification systems and is a crucial consideration in RAI decision-making. Therefore, we need individualized treatment plans.

Clinical characteristics and prognostic analysis of metachronous bilateral breast carcinoma: a retrospective study based on propensity score matching.

To investigate clinical characteristics, treatment, outcomes, and prognostic risk factors of metachronous bilateral breast carcinoma (MBBC) and provide a theoretical basis for clinical management of MBBC. This was a retrospective study. From January 1, 2010 to March 31, 2022, a total of 23,010 patients with breast cancer underwent surgical treatment at the Breast Center of the Fourth Hospital of Hebei Medical University, including 386 patients with MBBC. Propensity score matching (PSM) was performed on MBBC patients and unilateral breast cancer (UBC) patients in a 1:1 ratio, and 210 UBC patients and 210 MBBC patients were finally matched. Clinical medical records of all patients were collected, including age of onset, family history of breast cancer, tumor size, lymph node status, TNM stage, mode of surgery, menstruation, pathological type, immunohistochemical (IHC) typing, treatment, disease-free survival (DFS), and overall survival (OS). The result showed that age of onset of the second primary cancer (SPC) was significantly older than that of the first primary cancer (FPC) (P = 0.024). Baseline data from MPPC patients showed that the tumor size of FPC was significantly larger than that of SPC (P = 0.043), and the proportion of PR ( +) in FPC is significantly higher than that in SPC (P = 0.045). Among MBBC patients with FPC for estrogen receptor (ER) or progesterone receptor (PR) ( +) and Her-2 (-), clinical characteristics and treatment results showed that the proportion of PR ( +) in the drug-resistant group was significantly lower than that in the non-drug-resistant group. The 2-year OS rate of SPC in the drug-resistant group was significantly shorter than those of the non-drug-resistant group (78.9% vs 100%, P < 0.05). The result of PSM-based comparison between MBBC patients and UBC patients showed significantly lower proportion of MBBC patients with SPC received chemotherapy compared to UBC patients (P = 0.026), and there was no significant difference in OS and DFS between SPC course of MBBC patients and UBC patients (P > 0.05). The univariate analysis showed that high TNM stage was a risk factor for death and disease progression in MBBC patients, with the risk of death in stage III MBBC patients being about 5 times higher than that in stage I MBBC patients (HR = 4.97, 95%CI = 1.42-17.31, P = 0.012), and the risk of disease recurrence being about 3.5 times higher than that in stage I MBBC patients (HR = 3.55, 95%CI = 1.07-11.81, P = 0.039). In summary, this study presented clinical characteristics, treatment options, and outcomes of MBBC patients and patients with MBBC who were resistant to endocrine therapy have a worse SPC survival prognosis. The course of SPC in MBBC patients was similar to that of UBC in terms of prognosis and survival, which suggested that SPC can be treated according to UBC treatment regimen. High TNM stage was a prognostic risk factor for SPC patients.

Long-term follow-up of protective effects on salivary and swallowing structures and improvement of late xerostomia and dysphagia by level IIb optimisation in clinical target volume of nasopharyngeal carcinoma.

This study aimed to assess the long-term effect of level IIb clinical target volume (CTV) optimisation on survival, xerostomia, and dysphagia in patients with nasopharyngeal carcinoma (NPC). Clinical data of 415 patients with NPC treated with intensity-modulated radiotherapy between December 2014 and October 2018 were retrospectively analysed. The patients were categorised into modified and comparison groups. Late xerostomia and dysphagia were evaluated using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer scoring. Survival analysis was performed using the Kaplan-Meier method. Differences in late toxicity and dose parameters between both groups were compared. Prognostic factors for survival and late toxicity were assessed using regression analyses. Patients in the modified group developed late xerostomia and dysphagia less frequently than those in the comparison group did (P < 0.001). The mean dose (Dmean) and V26 of parotid glands; Dmean and V39 of submandibular glands; and Dmean of sublingual glands, oral cavity, larynx, and superior, middle, and lower pharyngeal constrictor muscles were lower in the modified group than those in the comparison group (all P < 0.001). Both groups had no significant differences in overall, local recurrence-free, distant metastasis-free, or progression-free survival. The Dmean of the parotid and sublingual glands was a risk factor for xerostomia. The Dmean of the parotid and sublingual glands and middle pharyngeal constrictor muscle was a risk factor for dysphagia. Level IIb optimisation in NPC patients who meet certain criteria specially the exclusion of positive retropharyngeal nodes treated with intensity-modulated radiotherapy has the potential to better protect the salivary and swallowing structures, decreasing the development of late radiation-induced xerostomia and dysphagia while maintaining long-term survival.

Efficacy of immunotherapy in advanced gastric cancer: preliminary results of a multicenter observational study

Background: Due to the low efficacy of PD-L1 antibodies in second and subsequent lines of metastatic gastric cancer (mGC), the optimal treatment strategy of such patients and appropriate choice of predictive biomarkers remain challenging. The aim of our study is to assess the efficacy of immune checkpoint inhibitors monotherapy in patients with mGC in routine clinical practice, especially in heavily-pretreated patients. Materials and methods: We retrospectively analyzed data of patients treated in five oncology centers in Moscow between 2018 and 2023, who received nivolumab or pembrolizumab for advanced gastric cancer. Primary end-point of our study was 6-months PFS. Secondary end-points were overall survival (OS), objective respons e rate (ORR), and disease control rate (DCR). Toxicity was assessed using CTC AE v5.0 scale. Results: 122 patients with mGC who received immune checkpoint inhibitors were included between 1 January 2018 and 28 February 2023. 6-months PFS rate was 31,6 %. The median OS was 7 months (95 % CI: 2–20), the median PFS was 3 months (95 % CI: 1,5–9,5). A statistically significant difference in OS was detected in patients with MSI compared to MSS (25 months vs 6 months; 95 % CI: 0,21–0,86; HR: 0,43). A trend towards higher PFS was observed as well (10 months in MSI vs 3 months in MSS; 95 % CI:0,26–1,01; HR: 0,51). No statistical significance in PFS and OS according to PD-L1 CPS was found among patients with MSS. ORR and DCR were 36,6 % and 10,6 %, respectively. No cases of pseudoprogression or fatal immune-related AEs were observed. Conclusion: Our real-world data is consistent with published literature and the results from clinical trials. Further studies are needed to determine prognostic factors and to establish prognostic model of patients receiving ICIs for optimal treatment strategy of mGC.

Correlation between relative dose intensity of adjuvant S-1 chemotherapy and psoas muscle mass volume and survival after resection of pancreatic ductal adenocarcinoma: A retrospective study.

This study aimed to investigate the prognostic relationship between relative dose intensity (RDI) of adjuvant S-1 chemotherapy and psoas muscle mass volume (PMV) in patients with resected pancreatic ductal adenocarcinoma. We enrolled 105 patients with histologically confirmed pancreatic ductal adenocarcinoma who had undergone pancreatectomy. Adjuvant S-1 chemotherapy was administered to 72 (68.6%) of the 105 patients and not to the remaining 33 patients. Patients who received adjuvant S-1 chemotherapy were stratified into high- and low-RDI groups by the cutoff value for RDI. Five-year overall survival (OS) and relapse-free survival (RFS) rates were significantly higher in the high- than in the low-RDI group. Similarly, both the 5-year OS and RFS rates were significantly greater among patients in the high-PMV group than among patients in the low-PMV group. The RDI was an independent prognostic factor in our study patients. Furthermore, patients who received adjuvant S-1 chemotherapy were stratified into 3 groups: those with both high RDI and high-PMV, Group A; those with either high RDI or high PMV (but not both), Group B; and those with both low RDI and low-PMV, group C. There were statistically significant differences in 5-year OS and RFS between 3 patient groups (5-year overall survival: P = .023, 5-year relapse-free survival: P = .001). The area under the curve for the combination of RDI and PMV (0.674) was greater than that for RDI alone (0.645). A sufficient dosage of adjuvant S-1 chemotherapy is important in improving survival of patients with resected pancreatic ductal adenocarcinoma. A combination of RDI and PMV may predict the prognosis of patients with resected pancreatic ductal adenocarcinoma more effective than RDI alone.