Surgery versus definitive radiotherapy in the management of stage I-II small cell neuroendocrine carcinoma of the cervix: A systematic review and meta-analysis.

BackgroundThe objective of this study is to investigate small cell neuroendocrine carcinoma of the cervix (SCCC), using a retrospective clinicopathological characteristic and treatment approach.MethodWe retrospectively analyzed cases of early-stage SCCC, identified between 2006 and 2016, in women who received radical surgery and adjuvant chemotherapy with or without radiotherapy. Kaplan–Meier and one-way ANOVA analyses were performed.ResultA total of 37 cases of SCCC are presented in this study, of which 21 had stage IB1 SCCC, 12 had stage IB2, 3 had stage IIA1, and 1 had stage IIA2. All patients were treated with radical surgery and adjuvant chemotherapy, specifically, 26 with radical surgery followed by adjuvant chemotherapy plus radiation and 11 with neoadjuvant chemotherapy (NACT) followed by radical surgery. After a median follow-up time of 27 months (range, 8–115 months), the 2-year and 5-year disease-free survival rate for all patients was 51.9% and 34.1%, respectively, and the overall survival rate was 60.3% and 38.6%, respectively. Univariate analysis showed that International Federation of Gynecology and Obstetrics (FIGO) stage and tumor size may be a predictor of a poor prognosis. NACT and adjuvant radiation did not improve survival over adjuvant chemotherapy alone but should not be a significant independent prognostic factor for survival.ConclusionEven in patients with early-stage SCCC, the prognosis is poor, although FIGO stage and tumor size may act as surrogate factors prognostic of survival.

Organ preservation in the treatment of penile cancer: To cut or not to cut

Definitive pelvic radiation therapy improves survival in stage IVB neuroendocrine cervical carcinoma: A NeCTuR study

Purpose: With the approval of immunotherapies for a variety of indications, methods to assess treatment benefit addressing the response patterns observed are important. We evaluated RECIST criteria-based overall response rate (ORR) and progression-free survival (PFS) as potential surrogate endpoints of overall survival (OS), and explored a modified definition of PFS by altering the threshold percentage determining disease progression to assess the association with survival benefit in immunotherapy trials.Experimental Design: Thirteen randomized, multicenter, active-control trials containing immunotherapeutic agents submitted to the FDA were analyzed. Associations between treatment effects of ORR, PFS, modified PFS, and OS were evaluated at individual and trial levels. Patient-level responder analysis was performed for PFS and OS.Results: The coefficient of determination (R²) measured the strength of associations, where values near 1 imply surrogacy and values close to 0 suggest no association. At the trial level, the association between hazard ratios (HR) of PFS and OS was R2 = 0.1303, and between the odds ratio (OR) of ORR and HR of OS was R2 = 0.1277. At the individual level, the Spearman rank correlation coefficient between PFS and OS was 0.61. Trial-level associations between modified PFS and OS ranged between 0.07 and 0.1, and individual-level correlations were approximately 0.6. HRs of PFS and OS for responders versus nonresponders were 0.129 [95% confidence interval (CI), 0.11-0.15] and 0.118 (95% CI, 0.11-0.13), respectively.Conclusions: Although responders exhibited longer survival and PFS than nonresponders, the trial-level and individual-level associations were weak between PFS/ORR and OS. Modifications to PFS did not improve associations. Clin Cancer Res; 24(10); 2268-75. ©2018 AACRSee related commentary by Korn and Freidlin, p. 2239.

Comparative effectiveness of primary radiotherapy versus surgery in elderly patients with locally advanced oropharyngeal squamous cell carcinoma

Small-cell neuroendocrine carcinoma of the cervix (SCNCC) is a rare and aggressive tumor with a poor prognosis. Surgical resection followed by adjuvant therapy is the standard treatment for early-stage disease but the influence of different neo/adjuvant treatment approaches remains unclear. Retrospectively, we collected patients' characteristics and treatments in two medical centers. Disease status and survival outcomes were renewed through follow-up. Statistics analysis mainly included Kaplan-Meier methods for survival curve estimation, log-rank test for survival curve comparison, and Cox proportional hazards models for independent prognostic factors prediction. Finally, 51 patients treated by radical surgery between January 2010 and April 2020 were enrolled with a median age of 50 years (range: 32-68). 12 (23.5%) patients were at stage IIIC1 according to the International Federation of Gynecology and Obstetrics (FIGO) 2018 staging systems and the rest were at the early stage. The mean tumor size was 3.6±1.3 cm. Pathological examination found 24 cases with pure SCNCC and 27 cases with admixed SCCC. 29 (56.9%) patients had deep stromal infiltration and 19 (37.3%) patients had lymphovascular space invasion. 34 (66.7%) patients received neo/adjuvant chemotherapy and pelvic radiation was conducted in 41 (80.39%) patients with a median dose of 46 Gy (range: 40-50.4 Gy). The median follow-up time was 25.0 months. The median disease-free survival (DFS) time was 23.0 months. 27 (52.9%) patients developed distant metastasis and 14 (27.5%) experienced local failure. The median overall survival (OS) was 32.0 months. Univariate and multivariate analysis showed neoadjuvant chemotherapy as negative (HR=2.081, 95% CI 1.030-4.203, p=0.041) and adjuvant chemotherapy (HR=0.409, 95% CI 0.213-0.784, p=0.020) as positive independent prognostic factor for DFS. For OS, only lymph node metastasis was confirmed as an independent prognostic factor in both univariate analysis (HR=1.528, 95% CI 1.011-2.308, p=0.044) and multivariate analysis (HR=1.697, 95% CI 1.041-2.768, p=0.034). In conclusion, for surgically treated SCNCC, adjuvant chemotherapy showed a positive influence on DFS while neoadjuvant chemotherapy harmed DFS. OS was unaffected by either treatment choice.

ESMO Clinical Practice Guideline update on the use of immunotherapy in early stage and advanced renal cell carcinoma

Small cell neuroendocrine carcinoma of the cervix: Analysis of outcome, recurrence pattern and the impact of platinum-based combination chemotherapy

State of the art of surgery in advanced epithelial ovarian cancer

Background: Standardized definitions of efficacy endpoints are needed to improve clinical trial designs, data reporting and interpretation of results, and to allow cross-trial comparisons. STEEP (Standardized Definitions for Efficacy Endpoints) criteria were proposed in 2007 by an expert panel from the National Cancer Institute (NCI) to provide common definitions for clinical trials in early breast cancer (BC). Invasive disease-free survival (IDFS) was selected as a candidate surrogate endpoint for overall survival (OS) in adjuvant trials and has been widely used in the last 15 years. Advances in BC systemic treatment led to review these criteria (STEEP v2.0), with the definition of a new modified endpoint: invasive BC-free survival (IBCFS). IBCFS excludes second primary non-breast invasive cancers from IDFS which may better detect efficacy effects when the toxicity profile of the intervention is well-known and the risk of second primary cancer is small. Methods: We proposed a multi-trial analysis of 8 adjuvant chemotherapy (CT) trials from GEICAM and TRIO to evaluate the different surrogate endpoints defined in the STEEP v2.0. Trial-level surrogacy was assessed through correlation between the ln hazard ratio (HR) of OS and the ln HR of the different studied endpoints across trials. The correlation was estimated by the weighted, by trial size, least squares regression (WLS) line and evaluated comparing the R2 values between OS and the corresponding endpoint tested. Primary analyses evaluated the correlation of OS with IDFS/IBCFS. Secondary analyses evaluated the correlation of OS with other STEEP v2.0 endpoints (distant disease-free survival [DDFS], distant relapse-free survival [DRFS], recurrence-free survival [RFS], recurrence-free interval [RFI] and distant recurrence-free interval [DRFI]) and explored the surrogacy between OS and all endpoints in specific groups of patients (pts) according to their risk of relapse: hormone receptors positive (HR+)/HER2-negative (HER2-) pts with intermediate/high and high-risk and triple negative (TN) pts. Results: A total of 14,473 pts were included. Median age was 50 years (range, 20–82). All were female, and 51.8% were postmenopausal. With a median follow-up of 115 months (range, 0.0–188) we found 2,504 OS events, 4,146 IDFS events (60.9% being distant recurrences) and 3,810 IBCFS events (62.4% being distant recurrences). For each trial, HR of OS, IDFS and IBCFS indicated same conclusions. If HR< 1 for OS, it was also for IDFS and IBCFS and the same was true when HR >1. R2 results of the weighted linear correlations between the ln HR of OS versus (vs) IDFS and OS vs IBCFS were 0.86 and 0.89, respectively. Confidence intervals (CI) at 95% were both overlapping. All other efficacy endpoints showed strong correlation with OS in the overall analysis. R2 values for HR+/HER2- intermediate/high and high-risk pts were 0.89 (OS vs IDFS) and 0.84 (OS vs IBCFS). For TN pts the correlations were weaker, being 0.63 (OS vs IDFS) and 0.73 (OS vs IBCFS). All WLS R2 values are described in the table. Conclusions: All tested STEEP v2.0 endpoints were strongly correlated with OS (R2 close to 1), meaning that their use as surrogate endpoints for adjuvant CT trials is appropriate. Notably, no differences were found between them in this multi-trial analysis. Therefore, none of them is more appropriate than other to discriminate the value of a new intervention vs comparator in adjuvant CT studies with mature data and long-term follow-up. Table: Citation Format: Sara López-Tarruella, Marina Pollan, Ander Urriticoechea, Eva Carrasco, Gonzalo Spera, Miguel Martín, Begoña Bermejo, Linnea Chap, Manuel Ruíz - Borrego, John Crown, Jose Angel García-Sáenz, Arlene Chan, Angel Guerrero, Valerie Bee, Lourdes Calvo, Rodrigo Fresco, Andrea Blasco, Andrés Hernando, Dennis Slamon. STEEP criteria v2.0 validation: A multi-trial analysis using GEICAM and TRIO adjuvant trials to evaluate surrogate endpoints for overall survival [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-03-03.

Evaluation of Primary Treatment Technique for Squamous Cell Carcinoma of the Buccal Mucosa: A Single-Center Experience

3584 Background: Many patients with CRC develop CRLM during their disease, which are associated with poor prognosis. In the phase 3 SUNLIGHT trial, the addition of BEV to FTD/TPI significantly improved overall survival (OS) compared with FTD/TPI alone in patients with refractory mCRC, irrespective of mutational status, tumor sidedness, and other factors associated with poor prognosis. Here, we assessed the impact of baseline CRLM on efficacy outcomes among patients treated in SUNLIGHT. Methods: In this post hoc analysis, OS, progression-free survival (PFS), and disease control rate (DCR) were assessed in patients with and without CRLM. Differences in survival between FTD/TPI + BEV and FTD/TPI alone were assessed in each subgroup. The Kaplan-Meier method and log-rank test were used to compare differences in OS and PFS; DCRs were compared using Fisher's exact tests. The hazard ratios (HRs) for OS and PFS were estimated using a Cox proportional hazards model. Results: Of the 492 patients enrolled in SUNLIGHT, 382 (77.6%) had CLRM, comprising 194 randomized to FTD/TPI + BEV and 188 randomized to FTD/TPI alone. Among patients randomized to FTD/TPI + BEV (n=246), median OS (95% confidence interval [CI]) was 10.4 (8.6, 11.0) months and not estimable (NE) (11.1–NE) for patients with and without CRLM, respectively (HR: 1.88; P=0.005). For patients randomized to FTD/TPI alone (n=246), median OS (95% CI) was 6.5 (5.9, 8.0) months and 10.9 (9.0, 13.8) months for patients with and without CRLM, respectively (HR: 1.75; P=0.002). Similar trends were observed for PFS and DCR. When comparing treatment effects across arms, FTD/TPI + BEV resulted in longer OS and PFS compared with FTD/TPI alone in patients with and without CRLM. In patients with CRLM, the HRs for OS and PFS were 0.61 (95% CI: 0.48, 0.77; P<0.001) and 0.44 (95% CI: 0.35, 0.55; P<0.001), respectively. In patients without CRLM, the HRs for OS and PFS were 0.60 (95% CI: 0.35, 1.0; P=0.052) and 0.38 (95% CI: 0.24, 0.58; P<0.001), respectively. The DCR was also higher in patients treated with FTD/TPI + BEV compared with FTD/TPI alone (68.6% vs 38.3% in patients with CRLM and 73.1% vs 53.5% in patients without CRLM). Conclusions: The results of this analysis show that patients treated with the combination of FTD/TPI + BEV had numerically longer OS and PFS and a higher DCR than those treated with FTD/TPI alone, irrespective of whether or not patients had CRLM at baseline. Owing to the imbalance in numbers of patients with and without CRLM, the data need to be interpreted with caution. Clinical trial information: NCT04737187 .

Clinical Outcomes Associated with <i>NPM1</i> Mutations in Newly Diagnosed AML

e18124 Background: Primary radiotherapy (RT) and primary surgery (PS) are considered equally viable local therapy modalities for oropharyngeal squamous cell carcinoma (OPSCC). The relative efficacy and toxicity of these competing therapies are often debated, and treatment choice is based on a paucity of comparative data. Methods: Eligible individuals were elderly patients in the SEER-Medicare registry diagnosed with OPSCC between 2000 and 2011. Patients were categorized as receiving either primary RT +/- chemotherapy, or PS +/- adjuvant RT or chemoradiotherapy (CRT). Overall survival (OS) was analyzed using Cox multivariable analysis (MVA). Risks of gastrostomy dependence (GD), esophageal stricture (ES), and osteoradionecrosis (ORN) at 1 year were determined through claims and analyzed using logistic regression. Results: A total of 3,804 patients (70% RT, 30% PS) were included in this cohort. At a median follow-up of 24.2 months, median and 2-year OS were 37.9 months and 61.1%, respectively. Patients treated with RT and PS experienced 2-year OS and median survival outcomes of 58.5%/34.9 months and 66.4%/48.0 months, respectively (p &lt; 0.001). In early-stage OPSCC, MVA found older age, unmarried status, increasing comorbidity, SEER region, tumor site, and no prior PET associated with inferior OS; treatment was not associated with OS. For locally advanced OPSCC, increasing age, unmarried status, increasing comorbidity, lower income, tumor site, higher stage, no prior PET, and RT alone (HR = 1.24 for RT alone vs. PS, p = 0.0020, whereas HR 1.08 for CRT vs. PS, p = 0.1955) were associated with inferior OS. Multivariable predictors of ES (9.5% of cohort) were SEER region, grade, and PS treatment (OR = 1.03 and 0.70 for RT and CRT vs. PS, p = 0.015). Independent predictors of GD at 6 months (21.5%) included married status, smoking, tongue site, advanced stage, and CRT treatment (OR = 1.13 and 2.30 for RT and CRT vs PS, p &lt; 0.001). The 1 year risk of ORN was 3.8% and not associated with treatment. Conclusions: Without a clearly dominant modality in elderly patients, local therapy decisions for OPSCC must be individualized to each patient’s disease and functional status.

BackgroundThe combination of immune checkpoint inhibitors (ICIs) and chemotherapy is known to improve overall survival (OS) in patients with extensive-stage small cell lung cancer (ES-SCLC). ICIs have different response patterns and survival kinetics characteristics from those of the traditional chemotherapy. In first-line treatment for ES-SCLC, there is an urgent need for surrogate endpoints for the early and accurate prediction of OS. This study aimed to assess progression-free survival (PFS), milestone OS rate, milestone restricted mean survival time (RMST), overall response rate (ORR), and disease control rate (DCR) as proposed surrogate endpoints for OS in ES-SCLC for first-line immunotherapy trials.MethodsBetween January 1, 2013, and December 2020, published articles on randomized clinical trials of ICIs plus chemotherapy in patients with ES-SCLC as first-line therapy were searched in PubMed. s from the ESMO, ASCO, and WCLC, reported from 2018 onwards, were also searched. A weighted regression analysis based on the weighted least squares method was performed on log-transformed estimates of treatment effect, and the determination coefficient (R2) was calculated to evaluate the association between treatment effect on the surrogate endpoint and OS.ResultsSeven trials, representing 3,009 patients, were included to make up a total of 16 analyzed arms. The ratio of the 12-month OS milestone rate (r = −0.790, P = 0.011, R2 = 0.717) and 12-month OS milestone RMST (r = 0.798, P = 0.010, R2 = 0.702) was strongly correlated with the hazard ratio (HR) for OS. The strongest association was observed between the ratio of the 24-month OS milestone RMST and the HR for OS (r = 0.922, P = 0.001, R2 = 0.825). No associations were observed between the HR for OS and PFS and the RR for ORR and DCR.ConclusionsThe results suggested a strong correlation among the ratio of OS milestone rates at 12 months, ratios of OS milestone RMSTs at 12 and 24 months, and HR for OS. The results indicate that OS milestone rates and OS milestone RMSTs could be considered surrogate endpoints of OS in future first-line immunotherapy trials for ES-SCLC.