Efficacy and Benefit of Postoperative Chemotherapy in Micropapillray or Solid Predominant Pattern in Stage IB Lung Adenocarcinoma: A Systematic Review and Meta-Analysis

Background: The benefit of postoperative chemotherapy remains controversial for patients with either a micropapillary or solid pattern in stage IB non-small cell lung cancer. This study is designed to explore the significance of postoperative chemotherapy in patients with either a micropapillary or solid pattern in stage IB lung adenocarcinoma.Method: To conduct the meta-analysis, PubMed, Cochrane Library, Embase and Medline were used to collect literature on long-term follow-up studies published before March, 2021, involving postoperative chemotherapy for patients with both a micropapillary or solid pattern in stage IB lung adenocarcinoma as compared to non-postoperative chemotherapy. Survival data was extracted from the literature, including the overall survival and disease-free survival. Based on overall survival and disease-free survival, hazard ratios and their 95% of confidence intervals were applied to assess the prognostic effect of postoperative chemotherapy. Review Manager software was used to merge the effect size for the meta-analysis.Result: In total, 6 papers with 956 patients were included. In terms of the prognosis of patients suffering from lung cancer when receiving postoperative chemotherapy, this study comprehensively reviews and evaluates the available evidence of micropapillary or solid patterns. After excluding the heterogeneity between the studies, we found that the pooled results from 6 studies report that postoperative chemotherapy was associated with a better overall survival rate when compared with non-postoperative chemotherapy (hazard ratio = 0.58, 95% confidence interval, 0.44–0.77; P = 0.0002). Postoperative chemotherapy also significantly improved the disease-free survival in patients with either a micropapillary or a solid pattern in stage IB lung adenocarcinoma (postoperative chemotherapy vs. non-postoperative chemotherapy, hazard ratio = 0.51, 95% confidence interval, 0.40–0.64; P < 0.001). However, a subgroup analysis showed that compared with non-postoperative chemotherapy, tumor size was unrelated to the prognosis of patients in stage IB undergoing postoperative chemotherapy (hazard ratio = 0.98, 95% confidence interval, 0.94–1.02; P = 0.27).Conclusion: Postoperative chemotherapy results in a better long-term survival rate for patients with either a solid or a micropapillary pattern in stage IB lung adenocarcinoma. Multi-center, prospective, clinical trials are needed to validate our findings.

Pretreatment C-Reactive Protein/Albumin Ratio is Associated With Poor Survival in Patients With 2018 FIGO Stage IB-IIA HPV-Positive Cervical Cancer

Objectives: The present study aimed to identify the predictive value of inflammatory indexes stratified according to human papillomavirus (HPV) infection status in women with FIGO 2018 stage IB∼IIA cervical cancer. We also explored the influences of HPV infection status on the survival of cervical cancer patients.Methods: We collected data for 583 women with stage IB∼IIA cervical cancer in Sun Yat-sen University Cancer Center between 2009 and 2017. The t-test, chi-squared (χ2) test and Fisher’s exact test were applied to compare the differences of inflammatory indexes and clinicopathological features between HPV-positive and HPV-negative groups. Univariate and multivariate analyses were used to identify clinicopathological factors that were associated with the prognosis of cervical cancer patients.Results: There were no differences in overall survival (OS) and progression-free survival (PFS) between HPV-positive and HPV-negative groups. In HPV-positive group, the maximum tumor size, neoadjuvant chemotherapy and the body mass index (BMI) correlated significantly with C-reactive protein/albumin ratio (CAR). The maximum tumor size and the prognostic nutritional index (PNI) correlated significantly with the platelet-lymphocyte ratio (PLR). The maximum tumor size, neoadjuvant chemotherapy and PLR correlated significantly with PNI. Univariate and multivariate analyses showed that the depth of tumor invasion (HR: 3.651, 95% CI: 1.464–9.103, p = 0.005; HR: 2.478, 95% CI: 1.218–5.043, p = 0.012) and CAR (HR: 5.201, 95% CI: 2.080–13.004, p < 0.0001; HR: 2.769, 95% CI: 1.406–5.455, p = 0.003) were independent predictors of poor OS and PFS. PNI was an independent protective factor of OS (HR: 0.341, 95% CI: 0.156–0.745, p = 0.007). PLR was an independent factor of PFS (HR: 1.991, 95% CI: 1.018–3.894, p = 0.044). In HPV-negative group, BMI correlated significantly with CAR. Only depth of invasion (HR: 9.192, 95% CI: 1.016–83.173, p = 0.048) was the independent predictor of poor OS, and no inflammation indexes were independent predictors of prognosis.Conclusion: In patients with HPV-positive cervical cancer, depth of invasion, PNI and CAR are independent factors of OS, and depth of invasion, PLR and CAR are independent factors for PFS. For patients with HPV-negative disease, no inflammation indexes had predictive value for prognosis. The predictive value of inflammation indexes on prognosis is more significant in patients with HPV-positive cervical cancer. Stratification of HPV infection status promotes a more precise clinical application of inflammation indexes, thus improving their accuracy and feasibility.

Treatment of Early-Stage Nodular Lymphocyte-Predominant Hodgkin Lymphoma: A Subgroup Analysis of the Randomized German Hodgkin Study Group HD16 Study

Background: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity accounting for approximately 5% of all Hodgkin lymphoma (HL) cases. Pathological and clinical characteristics differ from classical HL (cHL). In contrast to cHL, the malignant cells in NLPHL are consistently positive for CD20 but stain negative for CD30. The clinical course of NLPHL is usually indolent and patients present with early-stage disease more frequently than in cHL. Patients and Methods: We investigated characteristics and outcomes of 85 patients with NLPHL (stage IB and stage II without risk factors) who had treatment within the randomized German Hodgkin Study Group HD16 study for early-stage HL. Results were compared to those from 495 cHL patients (stage IB and stage II without risk factors) treated within the same study. Patients were randomized between standard treatment consisting of 2 cycles of ABVD followed by consolidation radiotherapy and treatment guided by interim positron emission tomography after 2 cycles of ABVD (PET-2). PET-2-guided treatment consisted of 2 cycles of ABVD alone for patients with a negative PET-2 and 2 cycles of ABVD followed by consolidation radiotherapy for patients with a positive PET-2 (defined as a Deauville score ≥ 3). Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method including 95%-confidence intervals (95%-CI) and hazard ratios (HR) obtained from Cox regression models. Analyses were performed descriptively. Results: Overall, 62/85 NLPHL patients (73%) were male as compared to 254/495 cHL patients (51%) (p=0.0002). The median age was 37 years (range: 19-71 years) among patients with NLPHL and 36 years (range: 18-75 years) among patients with cHL (p=0.4380). Information on the histopathological growth pattern was available for 67/85 NLPHL patients of which 44 (66%) had a typical growth pattern. The PET-2 was positive in 39/85 NLPHL patients (46%) and in 171/495 cHL patients (35%) (p=0.0507). After a median observation time of 64 months, the 5-year PFS was 90.3% (95%-CI: 83.8-96.7%) for all 85 NLPHL patients and 90.8% (95%-CI: 88.1-93.5%) for all 495 cHL patients (HR=1.1; 95%-CI: 0.5-2.1). The 5-year PFS rates for PET-2-positive NLPHL (n=39) and cHL (n=171) patients were 89.3% (95%-CI: 79.4-99.2%) and 91.6% (95%-CI: 87.2-96%) (HR= 1.3; 95%-CI: 0.5-3.5), respectively. The 5-year PFS rates for PET-2-negative NLPHL (n=46) and cHL (n=324) patients were 91% (95%-CI: 82.7-99.4%) and 90.4% (95%-CI: 87-99.4%) (HR=0.85; 95%-CI: 0.3-2.4), respectively. PET-2-negative NLPHL (n=25) and cHL (n=152) patients treated with 2 cycles of ABVD alone had 5-year PFS rates of 83% (95%-CI: 67.8-98.2%) and 88.2% (95%-CI: 82.7-93.6%) (HR=1.5, 95%-CI: 0.5-4.5), respectively. In contrast, PET-2-negative NLPHL (n=21) and cHL (n=172) patients treated with 2 cycles of ABVD followed by consolidation radiotherapy had 5-year PFS rates of 100% and 92.3% (95%-CI: 88.1-96.5%) (HR=0; 95%-CI: 0), respectively. NLPHL patients with a typical growth pattern (n=44) had a 5-year PFS of 95.2% (95%-CI: 88.8-100%) whereas patients with an atypical growth pattern (n=23) had a 5-year PFS of 82.2% (95%-CI: 66.3-98%) (HR=2.5; 95%-CI: 0.5-11.2). A total of 9 NLPHL patients experienced disease progression or relapse during follow-up. The median time to NLPHL recurrence was 14 months (range: 1-89 months). There were 2 cases of second primary malignancies (1 case of malignant melanoma, 1 case of stomach cancer) among patients with NLPHL. No patient developed histological transformation into aggressive B-cell non-Hodgkin lymphoma. The 5-year OS rates were 100% and 98.6% (95%-CI: 97.5-99.7%) (HR=0; 95%-CI: 0) for patients with NLPHL and cHL, respectively. Conclusion: Taken together, the 5-year outcomes for patients with newly diagnosed early-stage NLPHL were similar to their counterparts with cHL. Thus, the current standard of care for early-stage cHL consisting of 2 cycles of ABVD followed by consolidation radiotherapy represents a highly active option also for the treatment of patients with the initial diagnosis of stage IB and stage II NLPHL without risk factors. Disclosures Fuchs: Takeda: Consultancy, Honoraria; Lukon: Honoraria; Celgene: Honoraria; BMS: Honoraria; MSD: Honoraria. von Tresckow: AstraZeneca: Honoraria, Other: congress and travel support; Kite-Gilead: Consultancy, Honoraria; BMS-Celgene: Consultancy, Honoraria, Other: congress and travel support; Amgen: Consultancy, Honoraria; AbbVie: Other: congress and travel support; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: congress and travel support, Research Funding; Pentixafarm: Consultancy, Honoraria; MSD: Consultancy, Honoraria, Other: congress and travel support, Research Funding; Roche: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other, Research Funding. Engert: Takeda: Consultancy, Honoraria, Research Funding; BMS: Honoraria, Research Funding; Astra Zeneca: Consultancy, Honoraria; Tessa Therapeutics: Consultancy; Amgen: Honoraria; ADC Therapeutics: Consultancy; MSD: Honoraria; Hexal: Honoraria.

The Okabayashi Radical Hysterectomy: Basic Principle and Step-by-Step Procedure

Abdominal radical hysterectomy is the standard operation for stage IB–IIB cervical cancer in the world, which was established by Professor Hidekazu Okabayashi in 1921. In this article, the basic principle and step-by-step procedure of Okabayashi radical hysterectomy are presented, especially for young doctors to understand clearly the important points of this surgery and to realize its radicality and safety for better survival and quality of life of patients with cervical cancer.

Deep Muscularis Propria Tumor Invasion Without Lymph Node Metastasis as a Unique Subclassification of Stage IB Gastric Cancer: A Retrospective Study

Background The prognosis difference based on the depth of tumor muscularis propria invasion in gastric cancer (GC) was still debated. Methods A total of 380 patients with pT2 GC after radical surgery were retrospectively analyzed, including 185 in superficial muscularis propria (sMP) group and 195 in deep muscularis propria (dMP) group. Results The overall survival (OS) was significantly better for patients in sMP group than for patients in dMP group (P=0.007). In multivariate analysis, depth of tumor invasion, pN stage, age, primary location, positive expression of p53, elevated maximal LDH, elevated initial CA19-9 and AFP level were independent prognostic factors for OS. The sMP group had a significantly better OS than dMP group (P=0.014) in pN0 stage. After further stratification, the survival outcomes were not significantly different between deep muscularis propria tumor invasion without lymph node metastasis (dMPN0) group (stage IB) and superficial muscularis propria tumor invasion with stage 1-2 lymph node metastasis (sMPN1-2) group (stage II) (P=0.100). Patients with adjuvant chemotherapy had a statistically better survival than those without in dMPN0 group (P=0.045) and dMPN0 patients with adjuvant chemotherapy had better OS than sMPN1-2 patients (P=0.015). In addition, greater postoperative survival could be observed in sMPN0 patients than dMPN0 patients in p53-positive group (P=0.002), and similar OS could be seen between dMPN0 patients with p53-positive and T2N1-2 patients (P=0.872). Conclusion As a unique subclassification of stage IB GC, appropriate adjuvant chemotherapy should be considered for patients with dMPN0 stage. In addition, positive expression of p53, elevated LDH could be potential factors in identifying the different prognoses for stage IB GC patients.

Intraepithelial Lymphocytes are Indicators of Better Prognosis in Surgically Resected Endometrioid-Type Endometrial Carcinomas at Early and Advanced Stages

Background: Tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) may be useful prognostic indicators in endometrial cancer. However, standardized assessment methods and the prognostic roles of these cells in different stage groups are unclear.Methods: Formalin-fixed paraffin-embedded tissue samples of 107 endometrioid-type endometrial carcinomas (EECs) comprising 60 stage IB and 47 stage IIIC or IVB cases were evaluated. CD3+ TILs, CD8+ TILs, CD68+ TAMs, and CD163+ TAMs were detected by immunohistochemistry, and their densities were evaluated by semiquantitative and quantitative methods. TILs within tumor epithelial cell nests (E-TILs) and those within the stroma at the invasive front (S-TILs) were evaluated separately for CD3+ and CD8+ cells. The “TIL score” was defined as the sum of semiquantitative scores of CD3+ E-TILs, CD3+ S-TILs, CD8+ E-TILs, and CD8+ S-TILs. For TAMs, the area of CD68+ and CD163+ cells in the invasive margin were semiquantitatively and quantitatively evaluated. Clinicopathological and prognostic implications of TILs and TAMs in stage IB and IIIC/IVB EECs were examined by Cox univariate and multivariate analyses.Results: By Cox univariate analyses, semiquantitatively low CD3+ E-TILs, low CD8+ E-TILs, and low “TIL score” were significantly correlated with worse prognosis in stage IB patients (P = 0.011, 0.040, and 0.039, respectively). Likewise, low CD3+ E-TILs and low CD8+ E-TILs, by both semiquantitative (P = 0.011 and 0.0051) and quantitative evaluations (P < 0.0001, and P = 0.0015) and low “TIL score” (P = 0.020) were significantly correlated with worse prognosis in stage IIIC/IVB patients. By Cox multivariate analyses, semiquantitatively low CD3+ E-TILs in stage IB (P = 0.030) and semiquantitatively low CD3+ E-TILs or “TIL score” in stage IIIC/IVB (P = 0.022 and 0.049, respectively) were independent worse prognostic factors. CD68+ or CD163+ TAMs were not correlated with prognosis in any patients.Conclusions: Semiquantitatively low E-TILs, possibly representing low degree of TILs, are correlated with prognosis in both early and advanced stage patients with EEC. In particular, CD3+ E-TILs and CD8+ E-TILs are potentially useful prognostic markers in patients with EEC regardless of the stage.

The result of adjuvant Vinorelbine plus Cisplatin in completely resected stage IB-IIIA non-small cell lung cancer at Hanoi Medical Unoversity Hospital

Background: Assess clinical, subclinical characteristics of stage IB-IIIA non - small cell lung cancer patients (NSCLC). Evaluating the result of adjuvant vinorelbine plus cisplatin in completely resected stage IB - IIIA NSCLC. Methods: Descriptive study of 70 patients completely resected stage IB - IIIA non - small cell lung cancer were received adjuvant vinorelbine plus cisplatin chemotherapy at Hanoi Medical University Hospital from 01/2016 to 6/2020. Results: The mean age of 56.94 years old, male: female ratio was 2.9:1. 23 (32.8%) patients had postoperative stage IB disease, 24 (34.3%) had stage IIA disease, 13 (18.6%) had stage IIB disease and 10 (14.3%) had stage IIIA disease. The major histological type was adenocarcinoma (78.6%). Median disease free survival was 29.10 ± 1.63 months, and 3 - year survival was 41%. Chemotherapy caused hematologic side effects in 66.67% of patients including neutropenia in 61.4% and grade 3/4 neutropenia in 28.1%. Non - hematologic toxic effects of chemotherapy were reported at low rates and almost mild (grade 1/2). Conclusions: The vinorelbine - cisplatin regimen is an effective regimen in the adjuvant treatment of non - small cell lung cancer, the study showed that the results in disease - free survival and overall survival were comparable to those of other studies in the world. The most common side effect was neutropenia, the other side effects were reported at low rate and usually mild.