Stage IB Disease Research Articles

Sequential chemoradiation versus radiation alone or concurrent chemoradiation in adjuvant treatment after radical hysterectomy for stage IB1-IIA2 cervical cancer (STARS Study): A randomized, controlled, open-label, phase III trial.

6007 Background: There are limited data from previous studies regarding whether the addition of chemotherapy to adjuvant radiation after radical surgery improves outcomes among patients with early-stage cervical cancer and adverse pathological factors. Methods: This was a prospective randomized trial including patients with FIGO 2009 stage IB1-IIA2 cervical cancer and squamous-cell, adenocarcinoma, or adenosquamous carcinoma with at least one adverse factor after radical hysterectomy. Patients were randomized 1:1:1 to receive adjuvant radiation alone, concurrent chemoradiation with weekly cisplatin (30-40 mg/m2), or sequential chemoradiation with cisplatin (60-75 mg/m2) plus paclitaxel (135-175 mg/m2) in 21 day cycles, given 2 cycles before and 2 cycles after radiotherapy respectively. The primary outcome was the rate of disease-free survival at 3 years. Results: A total of 1,048 patients were included in the study (350, radiation alone; 345, concurrent chemoradiation; and 353, sequential chemoradiation). Overall, the median follow-up was 56 months and the median age of patients was 48 years. Most patients (75%) had stage IB1 or IIA1 disease. The three groups were similar with respect to histologic subtypes, the rate of lymphovascular invasion, parametrial, surgical margin and deep stromal involvement, tumor grade, rate of use of minimally invasive surgery, and neoadjuvant chemotherapy, except for lymph-node involvement that was lowest in radiation alone arm. In the intention-to-treat population, sequential chemoradiation was associated with a higher rate of disease-free survival than radiation alone (3-year rate, 90·0% vs. 82·0%; HR 0·52; 95% CI, 0·35 to 0·76) and concurrent chemoradiation (90·0% vs. 85·0%; HR 0·65; 95% CI, 0·44 to 0·96), differences remained after adjustment for lymph-node involvement. Sequential chemoradiation was also associated with a higher rate of overall survival than radiation alone (5-year rate, 92·0% vs. 88·0%; HR for death from cancer, 0·58; 95% CI, 0·35 to 0·95). However, neither disease-free survival nor cancer death risk was different between patients treated with concurrent chemoradiation or radiation alone. Conclusions: In this trial, sequential chemoradiation, rather than concurrent chemoradiation, resulted in a higher disease-free survival and lower risk of cancer death than radiation alone among women with early-stage cervical cancer after radical surgery. Clinical trial information: NCT00806117.

High PD-1 expression level is associated with an unfavorable prognosis in patients with cervical adenocarcinoma

PurposeThe effectiveness of immunotherapy for cervical adenocarcinoma (CA) has not been demonstrated yet. Programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and CD8 may be used as biomarkers of response to immune therapy in CA patients. In the present study, we aimed to investigate whether the expression levels of PD-1, PD-L1, and CD8 can predict the prognosis of patients with CA and their response to immune checkpoint inhibition therapy.MethodsIn the present study, the clinical stage for all 82 patients with cervical adenocarcinoma was classified according to the guidelines of the International Federation of Gynecology and Obstetrics (FIGO); there were 5, 48, 5, 14, 8, and 2 patients with stage IA, IB, IIA, IIB, IIIB, and IVB disease, respectively. The levels of PD-1, PD-L1, and CD8 were analyzed by the immunohistochemical analysis of the formalin-fixed paraffin-embedded tumor samples. The correlation between the expression levels and patient prognosis was analyzed using the Kaplan–Meier method and univariate and multivariate Cox proportional hazard regression models.ResultsWe observed a significant inverse correlation between the expression of PD-1 and CD8 (p = 0.001, chi-square test). We also found a significant inverse correlation between the expression of PD-L1 and CD8 (p = 0.027). The overall survival and progression-free survival rates were significantly worse in patients with positive PD-1 expression (p = 0.031; p = 0.087, respectively).ConclusionOur results suggest that a high PD-1 expression is associated with a poor prognosis in patients with CA. Further research is necessary to identify the molecular mechanisms that mediate this association.

Malignant peritoneal cytology and decreased survival of women with stage I endometrioid endometrial cancer

BackgroundTo examine the association between malignant peritoneal cytology and survival in women with early-stage endometrioid endometrial cancer. MethodsThis is a retrospective cohort study using the Surveillance, Epidemiology, and End Results Program from 2010 to 2016. Women with stage I endometrioid endometrial cancer who had peritoneal cytology testing at hysterectomy were examined (N = 24,800). Characteristics and survival related to malignant peritoneal cytology were assessed. The propensity score inverse probability of treatment weighting was used to balance the measured covariates. FindingsMalignant peritoneal cytology was reported in 1081 (4.4%) women. In multivariable analysis, stage IB disease and moderately/poorly differentiated tumours were associated with an increased likelihood of malignant peritoneal cytology (both P < 0.05). In a weighted model, malignant peritoneal cytology was associated with decreased cause-specific survival (5-year rates, 92.1% versus 96.8%, hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.56–2.52) and overall survival (89.4% versus 93.1%, HR 1.41, 95% CI 1.16–1.72). In sensitivity analyses, malignant peritoneal cytology was associated with decreased overall survival in the high–intermediate-risk group (5-year rates, 77.8% versus 83.6%, HR 1.57, 95% CI 1.20–2.06) and decreased cause-specific survival in the low-risk group (95.4% versus 98.0%, HR 1.64, 95% CI 1.01–2.68). In the high–intermediate-risk group with malignant peritoneal cytology, postoperative chemotherapy was associated with improved overall survival compared to whole pelvic radiotherapy (5-year rates, 82.7% versus 64.6%, HR 0.36, 95% CI 0.14–0.96). This association was not observed in negative cytology cases (81.5% versus 79.7%, HR 0.78, 95% CI 0.53–1.14). InterpretationMalignant peritoneal cytology may be associated with decreased survival in stage I endometrioid endometrial cancer.

Preoperative Conization and Risk of Recurrence in Patients Undergoing Laparoscopic Radical Hysterectomy for Early Stage Cervical Cancer: A Multicenter Study

To investigate the factors associated with poorer oncologic outcomes in patients undergoing laparoscopic radical hysterectomy (LRH) for early stage cervical cancer. Multicenter retrospective study. Three gynecologic oncology referral centers. Patients with International Federation of Gynecology and Obstetrics 2009 stage IA (positive lymphovascular space invasion)-IB1 cervical cancer between January 2006 and June 2018. LRH (Piver type II-III hysterectomies). Lymph-node dissection was accomplished according to the tumor characteristics. Surgical and oncologic outcomes were analyzed. Overall, 186 patients met the inclusion criteria, 16 (8.6%) experienced a recurrence, and 9 (4.8%) died of the disease (median follow-up period 37.9 months). Surgery-related complications did not influence disease-free survival. All the recurrences (16/16; 100%) occurred in patients with stage IB1 disease (p = .02), and 15 (93.7%) in cases involving tumors ≥2 cm. No association between positive lymph node and recurrence was detected (p =.82). Patients who had a preoperative diagnosis through conization (93; 50%) had a significantly lower rate of recurrence than those who underwent cervical biopsy (93; 50%): 1/93 (1.1%) vs 15/93 (16.1%); p <.001). The subanalysis of patients with International Federation of Gynecology and Obstetrics stage IB1 cervical cancer showed that patients undergoing preoperative conization (vs cervical biopsy) were less likely to experience a recurrence (odds ratio 0.09; 95% confidence interval 0.01-0.55). We confirmed that LRH was associated with a recurrence rate similar to that reported in the Laparoscopic Approach to Cervical Cancer trial. Tumor size ≥2 cm represents the most important risk factor influencing disease-free survival. However, we found that preoperative conization plays a potentially protective role in patients with an IB1 tumor.

Clinical Analysis of Primary Pulmonary Lymphoepithelioma-like Carcinoma in 8 Patients

背景与目的淋巴上皮瘤样癌为罕见的上皮肿瘤，多来源于鼻咽部，也发生在前肠起源器官，如肺、胃、唾液腺和胸腺。原发性肺淋巴上皮瘤样癌（primary pulmonary lymphoepithelioma-like carcinoma, PPLELC）是一种罕见的非小细胞肺癌（non-small cell lung cancer, NSCLC），约占肺癌的0.9%。本文目的在于探讨PPLELC的临床病理特点、治疗方法以及预后情况。方法回顾性分析湖南省肿瘤医院2013年10月-2016年6月收治的PPLELC患者8例，对其临床资料及预后进行临床分析，以深入研究这种罕见的肺癌亚型。结果8例患者中，62.5%（5/8）为女性，中位年龄为51.5岁（41岁-64岁），大多数（87.5%）患者不吸烟，50.0%患者无症状，约37.5%为Ⅰ期，50.0%为Ⅲ期，12.5%为Ⅳ期。PPLELC的典型病理特征与未分化的鼻咽癌相同，其特点是分化较差的肿瘤细胞，具有大的泡状核和核仁突出，呈合胞体生长，伴有淋巴细胞浸润。免疫表型：癌细胞P63（100.0%, 6/6）、CK5/6（100.0%, 5/5）、CK（100.0%, 5/5）阳性。对8例患者的程序性死亡配体-1（programmed cell death-ligand 1, PD-L1）表达进行了检测，当≥5%的细胞膜染色时定义为PD-L1阳性，PD-L1表达频率为50.0%（4/8），肿瘤细胞阳性比例分数（tumor proportion score, TPS）波动在20.0%-70.0%。3例行表皮生长因子受体（epidermal growth factor receptor, EGFR）基因突变检测，结果呈阴性；2例行EML4-ALK融合基因检测，结果呈阴性；1例行KRAS、B-raf、C-kit、HER2、VEGFR1、VEGFR2检测，结果示KRAS野生型，B-raf、C-kit无突变，HER2、VEGFR1、VEGFR2中等表达。所有患者均接受了手术治疗，其中接受了辅助化疗者5例，其中Ib期2例，Ⅲa期2例，Ⅳ期1例；辅助放化疗者1例，分期为Ⅲa期，接受了新辅助化疗者1例，分期为Ⅲa期。截止至随访截止期，所有患者均存活，中位存活时间为57个月，3年和5年总生存率（overall survival, OS）分别为87.5%和50.0%；无病生存率（disease-free survival, DFS）分别为87.5%和50.0%。结论PPLELC是一种罕见但独特的NSCLC亚型，具有明显的临床病理学特征，通常发生于年轻的非吸烟患者，无性别倾向，并与EB病毒（Epstein-Barr virus, EBV）感染有关，组织形态及免疫组化是诊断的主要手段。大多数患者缺乏EGFR和ALK等常见基因突变，提示这些基因的突变与PPLELC的发生无关。PD-1和PD-L1可能是潜在的治疗靶点。与其他类型的NSCLC相比，大多数患者处于早期或局部晚期，预后较好。目前还没有针对这种罕见肿瘤的标准化治疗方案。早期以手术切除为主，中晚期或转移阶段则采用手术、化疗、放疗等多种治疗方式。由于其发病率低，为了确定其生物学特性和最佳治疗方案，还需要进一步的研究。

Evaluation of the 8th edition of the American joint committee on cancer’s pathological staging system in prognosis assessment and treatment decision making for stage T1-2N1 breast cancer after mastectomy

PurposeThe 8th edition of the American Joint Committee on Cancer (AJCC) pathological staging system for breast cancer considers biologic factors in addition to the anatomical features included in the previous systems. The purpose of this study was to determine the validity of the 8th AJCC staging system for T1-2N1 breast cancer and to assess the effect of additional chemotherapy and radiotherapy according to the new pathologic stages. MethodsThe cohort included patients from the Surveillance, Epidemiology, and End Results program (2010–2012) who had stage T1-2N1 invasive breast carcinoma and underwent mastectomy. All patients were restaged using the 8th AJCC staging system. The Kaplan–Meier method, Cox proportional hazards regression, and competing risks models were used for data analysis. ResultsWe identified 9908 patients including 3022 (30.5%), 3131 (31.6%), 1940 (19.6%), 1194 (12.1%), and 621 (6.3%) were classified with stage IA, IB, IIA, IIB, and IIIA disease, respectively. The 5-year breast cancer-specific survival (BCSS) was 97.3%, 94.3%, 88.3%, 84.0%, and 71.1% for stage IA, IB, IIA, IIB, and IIIA disease, respectively. Higher pathological stage was associated with a significantly higher risk of breast cancer-related death. Chemotherapy was associated with better BCSS regardless of the pathological stage, but radiotherapy was only associated with better BCSS in stage IIIA disease. ConclusionsThe 8th AJCC pathological staging system provides more refined stratification for T1-2N1 breast cancer patients after mastectomy and may meet the needs of the current trend of individualized decision making for chemotherapy and radiotherapy in this patient subset.

Prognostic Factors and Impact of Minimally Invasive Surgery in Early-stage Neuroendocrine Carcinoma of the Cervix

To investigate the prognostic factors and impact of minimally invasive surgery (MIS) in surgically treated early-stage high-grade (HG) neuroendocrine cervical carcinoma (NECC). Retrospective cohort study. Asan Medical Center, Seoul, Korea. Patients with International Federation of Obstetrics and Gynecology (2009) stages IB1 to IIA HG NECC. All patients underwent radical hysterectomy (RH) with a laparotomy or an MIS approach. Between 1993 and 2017, 47 patients with International Federation of Obstetrics and Gynecology stages IB1 to IIA1 HG NECC were initially treated with RH. Clinicopathologic variables of patients were retrospectively reviewed from electronic medical records. The median follow-up period was 28.2 months (interquartile range, 17.1-42). Stage IB1 disease was the most common (70.2%). Twenty-nine patients (61.7%) underwent RH by MIS. The overall survival (OS) and disease-free survival (DFS) rates were 63.8% and 38.3%, respectively. Lymph node metastasis and resection margin involvement were significant risk factors for DFS (hazard ratio [HR], 2.227; 95% confidence interval [CI], 1.018-4.871; p =.045 and HR, 6.494; 95% CI, 1.415-29.809; p =.016, respectively) and OS (HR, 3.236; 95% CI, 1.188-8.815; p =.022 and HR, 12.710; 95% CI, 1.128-143.152; p =.040, respectively). The Kaplan-Meier survival curves revealed no significant differences in OS and DFS between the laparotomy and MIS groups (50% vs 72.4% log-rank p =.196, 38.9% vs 37.9% p =.975). Lymph node metastasis and resection margin involvement were poor prognostic factors of survival outcomes in initially surgically treated early-stage HG NECC. No difference was observed in the survival outcomes between the MIS and laparotomy approaches.

Predictors of Distant Recurrence Following Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer.

The objective of this study was to characterize patients at an increased risk of distant metastasis (DM) following stereotactic body radiation therapy (SBRT) for stage I non-small cell lung cancer (NSCLC). We identified patients undergoing SBRT for stage I NSCLC between 2005 and 2016. Patients with a prior lung cancer diagnosis, receiving a biological effective dose <100 Gy, or receiving chemotherapy were excluded. Patients underwent pretreatment staging and were classified according to the American Joint Committee for Cancer (AJCC) 8th edition staging. The primary endpoint was DM. The Kaplan-Meier method and the Cox proportional hazards model were used for survival analysis and to identify predictors of DM. A total of 174 patients were included, with a median age 75 years (range, 49 to 96 y) and a median follow-up of 24 months (range, 3 to 123 mo). The 2- and 4-year cumulative incidences of DM were 14.2% and 19.1%, respectively. Patients who developed DM had worse overall survival versus patients developing a locoregional recurrence (P=0.023). On multivariable analysis, having stage IB disease (hazard ratio: 2.95; 95% confidence interval: 1.06-8.23; P=0.039) or a lower/middle lobe tumor (hazard ratio: 2.67; 95% confidence interval: 1.07-6.69; P=0.036) was associated with increased risk of DM. The 2-year cumulative incidences of DM were 10.9% and 35.7% (P=0.002) for patients with stage IA versus IB tumors, respectively, and 11.3% and 19.7% (P=0.049) for patients with upper lobe versus lower/middle lobe tumors, respectively. Patients with stage IB disease or lower/middle lobe tumors may have an increased risk of DM following SBRT. Randomized controlled trials are needed to further identify patients who may benefit from adjuvant systemic therapy after SBRT for stage I NSCLC.

Contributions of the newly revised 2018 international federation of gynecology and obstetrics staging of cervical cancer

Introduction. According to the latest data from International Agency for Research on Cancer from 2018, global burden of cancer cervical cancer is the fourth most common cancer in women worldwide. The aim of this article was to present the contributions of the new, revised 2018 International Federation of Gynecology and Obstetrics staging of carcinoma of the cervix uteri, allowing much more precise staging with the use of any imaging modalities and/or pathological findings to allocate the stage and provide more effective treatment. International Federation of Gynecology and Obstetrics staging system. The main changes in the new staging system were made in IB stage of the disease, which now includes 3 subgroups i.e. substages for every 2 cm increments in tumor size: stage IB1 (&lt; 2 cm), stage IB2 disease (2 to &lt; 4 cm), and stage IB3 (? 4 cm). This system also incorporates the lymph node status into stage III cervical cancer, allowing imaging and/or pathological findings of lymph nodes to the pelvic and/or para-aortic nodes to assign stage IIIC disease. Conclusion. The main goal of the new staging system revision was to improve the accuracy of staging in order to provide more refined understanding of prognostic groups and facilitate better treatment for women with invasive cervical cancer.

Laparoscopic vs. Abdominal Radical Hysterectomy for Locally Advanced Cervical Cancer

This study is to compare the survival outcomes of laparoscopic radical hysterectomy (LRH) to those of abdominal radical hysterectomy (ARH) for patients with locally advanced cervical cancer (LACC). Patients with the International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2 to IIB LACC who underwent radical hysterectomy between 2001 and 2015 were identified. The disease-free survival (DFS) and overall survival (OS) were compared according to the surgical approach and were adjusted based on clinicopathologic characteristics. A total of 396 patients were included in the study, with 179 (45.2%) and 217 (54.8%) patients in the ARH and LRH groups, respectively. The LRH group showed a significantly lower amount of estimated blood loss, lower blood transfusion rate and shorter length of hospital stay. Overall, there were no significant differences in the 5-year DFS and 5-year OS between the LRH and ARH groups with the Kaplan-Meier method. However, multivariate analyses identified LRH as an independent prognostic factor for a poor DFS (hazard ratio [HR] 2.5; 95% confidence interval [95% CI] 0.19 to 0.87; p = 0.02). The analysis of stage IB2 disease and the squamous subtype (61.9% and 87.9% of all participants, respectively) reached the same conclusion. When stratifying by FIGO stage, the patients with IB2 (n = 348) in the ARH group had a significantly better DFS (HR 0.14, 95% CI 0.05–0.42, p < 0.01) and OS (HR 0.17, 95% CI 0.04–0.67, p = 0.11) than those in the LRH group in the Cox regression model. However, no differences were found in patient with stage IIA1, IIA2, or IIB in Cox regression model. When stratifying by histological types, for the patients with squamous carcinomas (n = 375), in Cox model, ARH had a significantly superior DFS compared with those who underwent LRH (HR 0.45, 95% CI 0.25–0.82, p = 0.01), but the OS was not statistically significant (HR 0.57, 95% CI 0.27–1.20, p = 0.14). However, no differences were found in patient with adenocarcinoma and adenosquamous carcinomas in the Cox model. Therefore, ARH was associated with a higher DFS than LRH in patients with LACC, especially in patients with stage IB2 disease or the squamous subtype.

Retrospective analysis of treatment and prognosis for uterine leiomyosarcoma: 10-year experience of a single institute.

Uterine leiomyosarcoma (ULMS) is a highly aggressive and lethal disease. This malignancy remains the most common type of uterine sarcoma, affecting approximately 0.4/100000 women each year. Our aim was to assess the treatment and prognosis of ULMS patients. A total of 14 patients were treated at our institution between January 2008 and July 2017. We retrospectively analyzed their clinicopathological variables, treatment and prognosis. The median patient age was 63 years (range, 35-83 years). The largest group of patients had stage IB disease (stage IB, n=8; IIB, n=2; IIIB, n=1; IVB, n=3) and the largest group by histological subtype was ordinary (ordinary, n=11; myxoid, n=2; epithelioid, n=1). Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed for all patients, with additional surgical procedures (e.g., tumor resection, lymphadenectomy) performed if necessary. Twelve patients received adjuvant chemotherapy (ACT) consisting of gemcitabine and docetaxel. Ten patients experienced recurrence and received multidisciplinary therapies, including tumor resection, chemotherapy, radiation and targeted therapies. The median observation period was 17 months (range, 5-75 months), and 11 patients were alive (without disease, n=5; with disease, n=6). Intriguingly, five of eight stage IB patients who received postoperative ACT were alive without disease. ULMS is rare but is associated with a poor prognosis, even if multidisciplinary therapies are administered. However, ACT appears to be effective in improving the prognosis of patients with stage IB disease.

A proposal for a new classification of “unfavorable risk criteria” in patients with stage I endometrial cancer

BackgroundRandomized trials describe differing sets of high–intermediate risk criteria.ObjectiveTo use the National Cancer Database to compare the impact of radiation therapy in patients with stage I endometrial cancer meeting different...

AJCC 7th edition staging classification is more applicable than AJCC 8th edition staging classification for invasive IPMN

BackgroundBoth the 7th and 8th editions of the American Joint Committee on Cancer (AJCC) staging systems have been introduced for pancreatic adenocarcinoma. However, the applicability of these classifications for invasive intraductal papillary mucinous neoplasms (IPMN) has not been systematically examined.MethodsPatients with invasive IPMN were retrieved from a cohort of 18 geographical sites (1973–2014 varying) in the Surveillance, Epidemiology, and End Results (SEER) cancer registry. The 7th and 8th editions of the AJCC staging were compared. Survival rates and multivariate analyses were computed.ResultsIn total, 1216 patients with resected invasive IPMN were included. A major difference between the 7th and 8th systems is the definition of stage IIA (7th, beyond the pancreas without involvement of major arteries; 8th, maximum tumor diameter > 4 cm). The hazard ratio (HR) of stage IIA disease (versus stage IA, HR = 2.33, P < 0.001) was higher than that of stage IB disease (HR = 1.48, P = 0.087) by the 7th edition classification, whereas the HR of stage IIA disease (HR = 1.26, P = 0.232) was even lower than that of stage IB disease (HR = 1.48, P = 0.040) by the 8th edition classification. In addition, for the 8th edition staging system, tumor size was not a predictor of survival in patients with resectable tumor > 2 cm (size > 4 cm versus > 2 ≤ 4 cm, HR = 0.91, P = 0.420).ConclusionsThe AJCC 7th edition staging classification is more applicable than the 8th edition classification for invasive IPMN.

Stereotactic Ablative Body Radiotherapy Versus Radical Radiotherapy: Comparing Real-World Outcomes in Stage I Lung Cancer

AimsStereotactic ablative body radiotherapy (SABR) is now considered the standard of care for medically inoperable stage I non-small cell lung cancer (NSCLC). The English National Cancer Registration and Analysis Service (NCRAS) collects data on all patients diagnosed with lung cancer, including information on treatment. We wanted to compare outcomes for patients with stage I NSCLC treated with radical radiotherapy with either SABR or fractionated radiotherapy. Materials and methodsAll patients diagnosed with stage I NSCLC in 2015 and 2016 were identified from the NCRAS dataset, validated by the National Lung Cancer Audit, and their treatment data were collated. For patients who received radiotherapy, those receiving radical dose fractionations, including SABR, were identified through linkage to the national Radiotherapy Dataset. Clinical outcomes for those receiving SABR or more fractionated radical radiotherapy were compared using univariate and fully adjusted Cox proportional hazards models. ResultsIn total, 12 384 patients with stage I NSCLC were identified during the study period; 53.5% underwent surgical resection, 24.3% received no documented treatment, 18.6% received radical radiotherapy and 3.5% received other non-curative-intent treatments. For those receiving radical radiotherapy, 69% received SABR and 31% received fractionated treatment. The hazard ratio of death for the 1587 patients who received SABR was 0.69 (95% confidence interval 0.61–0.79) compared with 717 patients who received radical fractionated radiotherapy; this benefit was seen for both stage Ia and stage Ib disease. The median overall survival was also longer for SABR versus radical radiotherapy (715 days versus 648 days). Exploratory travel time analysis shows that compared with stage I NSCLC patients receiving SABR, those receiving fractionated radiotherapy and those receiving no active treatment would have to travel longer and further to reach their nearest radiotherapy SABR centre. ConclusionThis study adds to the data that SABR has a survival benefit when compared with fractionated radical radiotherapy. Although the use of SABR increased in England over this study period, it has still not reached levels of use seen in other countries. This study also highlights that one quarter of stage I NSCLC patients overall received no active treatment.

Impact of surgical approach on oncologic outcomes in women undergoing radical hysterectomy for cervical cancer

Recent studies demonstrating shorter survival among cervical cancer patients undergoing minimally invasive versus open radical hysterectomy could not account for surgeon volume and require confirmation in other jurisdictions with larger sample sizes, longer follow-up, and data on disease recurrence. To determine if surgical approach is associated with oncologic outcomes in cervical cancer patients undergoing minimally invasive or open radical hysterectomy, while accounting for mechanistic factors including surgeon volume. We performed a population-based retrospective cohort study of cervical cancer patients undergoing primary radical hysterectomy by a gynecologic oncologist from 2006 to 2017 in Ontario, Canada. A multivariable marginal Cox proportional hazards model and cause-specific hazards model were used to evaluate the association of surgical approach with all-cause death and recurrence respectively, clustering at the surgeon level. We tested for interactions between surgical approach and either pathologic stage or surgeon volume. We identified 958 patients (minimally invasive 475; open 483) with mean age 45.9 and a median follow-up of 6 years. Of minimally invasive procedures, 89.6% were performed laparoscopically and 10.4% robotically. The unadjusted 5-year cumulative incidences of all-cause death (minimally invasive 12.5%; open 5.4%), cervical cancer death (minimally invasive 9.3%; open 3.3%), and recurrence (minimally invasive 16.2%; open 8.4%) were significantly increased for minimally invasive radical hysterectomy in patients with stage IB disease, but not the cohort overall. After adjusting for patient factors and surgeon volume, minimally invasive radical hysterectomy was associated with increased rates of death (hazard ratio [HR], 2.20; 95% confidence interval [CI], 1.15-4.19) and recurrence (HR, 1.97; 95% CI, 1.10-3.50) compared to open radical hysterectomy in patients with stage IB disease (n= 534), but not IA disease (n= 244; HR, 0.73; 95% CI, 0.13-4.01; HR, 0.34; 95% CI, 0.10-1.10). Minimally invasive radical hysterectomy is associated with increased rates of death and recurrence in patients with stage IB cervical cancer even after controlling for surgeon volume; open radical hysterectomy should be the recommended approach in this population. Although there may be a subset of patients with microscopic early-stage disease for whom minimally invasive radical hysterectomy remains safe, additional studies are required.

Is the revised 2018 FIGO staging system for cervical cancer more prognostic than the 2009 FIGO staging system for women previously staged as IB disease?

ObjectiveThe purpose of this study was to compare the prognostic value of the revised FIGO staging system with that of the 2009 FIGO staging system for women previously staged as IB disease. MethodsInstitutional cervical cancer databases of two high-volume gynecologic cancer centers in Ankara, Turkey, were retrospectively analyzed. Only women with 2009 FIGO stage IB1 or IB2 disease who underwent primary surgery were included. Survival curves were generated using Kaplan-Meier plots, and the log-rank test was used for survival comparisons. The Cox proportional hazards regression model was used to obtain hazard ratios (HRs) and 95% confidence interval (CI). ResultsData from 425 women were analyzed. The 2009 FIGO stage IB2 (n = 131) disease was associated with a nearly three-fold increased risk of mortality when compared to the 2009 FIGO stage IB1 (n = 294) disease (HR: 2.72, 95% CI: 1.69–4.37; p < 0.001). Stage migration was observed in 372 (87.5%) patients, according to the revised FIGO staging system, leading to no significant difference in five-year overall survival rates between stage IB1 (n=53) and IB2 (n=127) disease (95.2% vs. 89.3%, respectively; p = 0.23),or between stage IB2 (n=127) and IB3 (n=95) disease (89.3% vs. 84.2%, respectively; p = 0.12). Similarly, there was no significant difference in five-year overall survival rates between stage IIIC1 (n=114) and IIIC2 (n=36) disease (79.0% vs. 67.2%, respectively; p = 0.34). ConclusionWhen compared to the 2009 FIGO staging system, the revised staging system has more sub-stages, which leads to fewer patients in each sub-stage, resulting in diminished statistical power.

&lt;p&gt;Intraperitoneal cytology after laparoscopic radical hysterectomy with vaginal closure without the use of a manipulator for cervical cancer: a retrospective observational study&lt;/p&gt;

PurposeAlthough laparoscopic radical hysterectomy (LRH) has been performed for patients with cervical cancer because of its minimal invasiveness, a recent large prospective study showed that LRH was associated with a lower rate of disease-free survival and overall survival. However, the reason for these results is not apparent. The aim of this study was to evaluate the tumor spillage during LRH with vaginal closure without the use of a manipulator.Patients and methodsTwenty-four patients with cervical cancer underwent total LRH with vaginal closure. To evaluate the leakage of cancer cells during surgery, peritoneal cytology was performed before and after hysterectomy.ResultsAmong 24 patients with cervical cancer, 2 had stage IA2 disease, 19 had stage IB1 disease and 3 had stage IIA1 disease. Two patients had lymph node metastasis. The median tumor size on final pathology was 9 mm. No cancer cells were identified before or after hysterectomy in any patients.ConclusionTotal LRH with vaginal closure did not increase the propensity for tumor spillage in the peritoneal cavity.

Uterine Artery–sparing Minimally Invasive Radical Trachelectomy: A Case Report and Review of the Literature

Radical trachelectomy is considered in patients with early-stage cervical cancer who desire future fertility. This article is accompanied by a video that provides step-by-step demonstration of a uterine artery-sparing robotic-assisted radical trachelectomy in a patient with stage IB1 squamous cell carcinoma of the cervix, a 2-cm mass, and a desire for future fertility. We also conducted a review of the literature examining the use of uterine artery-sparing techniques among minimally invasive radical trachelectomies. Using PubMed, Google Scholar, and Ovid search tools, 28 total publications were reviewed, of which 16 were eligible for use in our comparison. With the addition of our case report, a total of 154 cases sparing the uterine artery and 40 cases sacrificing the uterine artery were examined, including both conventional laparoscopic and robotic-assisted approaches. Data describing patient demographics as well as surgical, oncologic, and fertility outcomes were collected. The mean age was 30 years for the spared group and 32 years for the sacrificed group. At least 42% of the women in the spared and 53% of the uterine artery-sacrificed group were nulliparous. The majority of cases in both the spared and sacrificed groups represented squamous cell histology (71% for spared and 51% for sacrificed) followed by adenocarcinoma (24% vs 43%). The majority of the patients in both groups had stage IB1 disease (79% for spared vs 65% for sacrificed). The operative times among the 2 groups were similar, with a mean time of 314 minutes (range, 170-420 minutes) in the spared group and 283 minutes (range, 172-345 minutes) in the sacrificed group. The mean estimated blood loss was 173 mL (range, 23-300 mL) in the spared group and 77 mL (range, 50-250 mL) in the sacrificed group. The recurrence rates for the uterine artery-sparing and -sacrificing groups were equal at 2.6% after a mean follow-up of 42 months and 26 months, respectively. The methods of reporting fertility outcomes were varied among the different publications, with 41 patients achieving pregnancy in the spared group and 2 patients achieving pregnancy in the sacrificed group. Among patients who were not trying to conceive or had not conceived, 15 patients in the spared group and 6 patients in the sacrificed group were reported to have normal menses. The successful preservation of uterine arteries supports the maintenance of uterine arterial blood flow and is used by many gynecologic surgeons performing minimally invasive radical trachelectomy, with promising oncologic and obstetric outcomes.

ALINA: A phase III study of alectinib versus chemotherapy as adjuvant therapy in patients with stage IB–IIIA anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC).

TPS8569 Background: Patients with early-stage NSCLC (stage IA–IIIA) account for ~40% of cases at diagnosis; despite surgery, 5-year survival rates are low. Platinum-based adjuvant chemotherapy is the standard of care (SoC) for stage II–IIIA disease. Although patients with stage IA NSCLC do not benefit from adjuvant chemotherapy, patients with stage IB disease and large tumors (≥4cm) do. Adjuvant chemotherapy produces a 4–5% increase in 5-year survival rates, leaving significant unmet need for improved treatments. Approximately 5% of patients with NSCLC harbor an oncogenic fusion of the ALK gene. Treatment of advanced ALK+ NSCLC with ALK inhibitors improves efficacy and safety compared with chemotherapy. Alectinib, a potent ALK inhibitor, is the SoC first-line treatment for advanced ALK+ NSCLC. The ongoing ALINA trial will compare alectinib versus chemotherapy as adjuvant treatment for patients with stage IB–IIIA ALK+ NSCLC. Methods: ALINA is a randomized, multicenter, open-label phase III study investigating the efficacy and safety of adjuvant alectinib versus chemotherapy in ALK+ NSCLC (confirmed by an FDA-approved and CE-marked test). Adult patients (≥18 years) with completely resected stage IB (tumors ≥4cm) to IIIA disease and ECOG PS 0–1 are eligible for inclusion. Patients (N=255) from ~170 centers across ~30 countries will be randomized 1:1 to receive twice-daily alectinib 600mg for 24 months or four 21-day cycles of platinum-based chemotherapy (cisplatin 75mg/m2 [day 1] plus vinorelbine 25mg/m2 [days 1 and 8] or gemcitabine 1250mg/m2 [days 1 and 8] or pemetrexed 500mg/m2 [day 1]) according to local prescribing information. Stratification factors are disease stage (stage IB [≥4cm] vs stage II vs stage IIIA) and race (Asian vs non-Asian). Treatment will continue until planned completion, disease recurrence, unacceptable toxicity, withdrawal of consent, or death, whichever occurs first. The primary endpoint is disease-free survival per investigator; secondary endpoints are overall survival, safety, and pharmacokinetics. Clinical trial information: NCT03456076.

Survival differences based on tumor size among stage 1B cervical cancer patients in Louisiana using revised FIGO staging system.

e17017 Background: In the recently revised 2018 FIGO cervical cancer staging, stage IB is sub-classified into 3 classes based on tumor size. We aim to determine if larger tumor size confers worse survival outcomes in women with stage IB cervical cancer in Louisiana. Methods: Women with stage IB cervical cancer diagnosed between 2010 and 2016 were identified from the Louisiana Tumor Registry. Patients with positive pelvic or para-aortic lymph nodes and those with less than 30 days follow up were excluded. Subjects were classified into three groups based on tumor size: stage IB1 ( &lt; 2cm), stage IB2 (≥ 2cm and &lt; 4cm), and stage IB3 (≥ 4cm). Cox proportional hazards were used to estimate differences in overall (OS) and cause-specific survival (CSS). Covariates included age, race, insurance, census tract-poverty level, and marital status. Results: 198 patients were included with a median follow up time of 43.8 months. Mean age of patients in this cohort was 46.8 years. The subjects were well distributed between the groups: 79 (39.4%) stage IB1, 60 (30.3%) stage IB2, and 60 (30.3%) stage IB3. White women comprised a larger percentage of earlier stage tumors (79.5% 1B1 vs 68.3% 1B2 vs 53.3% 1B3, p &lt; 0.01); Black women were overrepresented in later stage disease (45.0% IB3, 28.3% IB2, 20.5% IB1, p &lt; 0.01). There were no significant differences between the three groups in age, insurance status, poverty level, or marital status. After adjusting for covariates, patients with stage 1B3 disease had worse survival than those with stage 1B1 disease in both OS [HR 6.01 (1.96,18.50)] and CSS [HR 24.31 (2.97,199.00)]. Patients with stage 1B2 disease had worse survival than those with 1B1 disease but this did not reach statistical significance: OS HR 1.88 (0.52,6.74); CSS HR 6.79 (0.77, 59.99). Kaplan-Meier curves of OS and CSS show significant survival differences between the three groups (p &lt; 0.0001) with best outcomes in stage 1B1 and worst in stage 1B3 patients. Conclusions: This analysis of contemporary stage IB cervical cancer patients in Louisiana confirms that tumor size &gt; 4cm confers worse clinical prognosis. Black women are overrepresented advanced stage IB disease. While patients with tumors 2-4cm did worse than those with tumors &lt; 2cm, this did not reach statistical significance. This could be due to the limited sample size of our cohort.