Stage IA Disease Research Articles

Recent Noteworthy Studies in Thoracic Oncology.

In this paper, we review recent prospective surgical studies on resectable esophageal and lung cancer. A narrative literature review was performed using the terms 'resectable esophageal cancer' and 'multimodal therapy' and 'resectable non-small cell lung cancer'. Prospective surgical trials performed from 2010 to 2023 were identified and analyzed. gov was queried for ongoing studies. The studies on esophageal cancer demonstrate the benefits of neoadjuvant chemoradiation, compared with surgery alone, and the emerging role of immunotherapy as part of induction and adjuvant treatment protocols. The selected studies on lung cancer demonstrate the evolving role of sublobar resection for patients with peripheral node-negative clinical stage IA1 disease and the developing role of neoadjuvant and adjuvant immunotherapy for patients with stage II-IIIA disease. The methods of treating patients with resectable esophageal or lung cancer are changing. Efforts to limit patient morbidity and optimize tumor treatment before surgery are increasingly being pursued and these approaches will likely continue to evolve as tumor biology and long-term pharmacologic mechanisms of action become clearer. Personalized medicine strategies that are based on tumor characteristics and the host genetic profile remain on the horizon, not yet ready for adoption in routine clinical practice.

Salvage interstitial brachytherapy for treatment of recurrent endometrial cancers in the vagina: Seven-year single institution experience and review of second recurrence patterns

IntroductionInterstitial brachytherapy (ISBT) is a known treatment for vaginal recurrence of endometrial cancer. This study reviews a large tertiary institution's ISBT experience and outcomes for vaginal recurrences. Material and MethodsPatients who underwent salvage ISBT for vaginal recurrence of endometrial cancer from January 1, 2014 - August 31, 2021, were identified. Initial and salvage disease factors and treatments were recorded. Outcomes were calculated including overall survival, local, and distant failure. ResultsThirty-nine patients were included; thirty received external beam radiotherapy and interstitial brachytherapy (EBRT + ISBT) while nine received ISBT alone. At initial diagnosis, the ISBT alone group had an older median age, with stage IA-IV disease, frequently receiving adjuvant treatment, compared to the EBRT with ISBT group with mainly stage IA disease who did not. Median follow up was 22 months and median time to recurrence 14 months (16.5 months in EBRT + ISBT group and 14 in the ISBT alone group). Two-year overall survival was 85% for all patients, 85.6% and 83.3%in the EBRT + ISBT and ISBT alone groups, respectively. Local failure was 22.7% for all patients,16.7% in the EBRT + ISBT group and 11.1% in the ISBT alone group. Median HRCTV D90 (EQD2) was 76.8 Gy in the EBRT + ISBT group, and 57.9 Gy in the ISBT alone group. Late grade 3 or higher toxicity occurred in only three patients. ConclusionsEBRT + ISBT is an effective treatment for endometrial cancer vaginal recurrence, with acceptable toxicity. ISBT alone is an option for patients with contraindications to or with previous treatment of pelvic radiation.

Non-Metastatic Uterine Carcinosarcoma: A Tailored Approach or One Size Fits All?

Purpose: Uterine carcinosarcomas are highly aggressive tumors of the endometrium and are associated with a poor prognosis. The optimal adjuvant treatment for both early and advanced-stage patients remains unclear. Methods: Cases of uterine carcinosarcoma were identified in our institution’s pathology database between 2000 and 2022. Kaplan–Meier estimates were calculated for the local and distant recurrence-free, disease-free and overall survival; hazard ratios were calculated using Cox proportional hazards modelling for independent prognostic factors including the stage and treatment. Results: A total of 48 patients were identified as having uterine carcinosarcoma, of whom 70.8% were surgically staged. In total, 43 patients had pelvic-confined disease, while five had positive omental or peritoneal biopsies at surgery. There were 10 pelvic (20.8%) and 19 (39.6%) distant recurrences. None of the patients with stage IA disease who received chemotherapy and brachytherapy experienced disease recurrence. The local recurrence-free survival was 54.95%, the distant recurrence-free survival was 44.7%, and the overall survival was 59.6% at 5 years. Local recurrence-free survival and overall survival were inversely associated with advanced-stage OR 1.23 (p = 0.005) and OR 1.28 (p = 0.017), respectively, and no chemotherapy was associated with OR 1.96 (p = 0.06) and OR 2.08 (p = 0.056), respectively. Conclusion: The local and distant recurrence rates were high for advanced=stage patients even when treated with aggressive adjuvant therapy regimens. Chemotherapy may improve recurrence and survival. Early-stage patients may perform well with vaginal vault brachytherapy and chemotherapy. Further prospective comparisons are required between sequential, sandwich, and concurrent approaches to chemotherapy and radiotherapy, to optimize outcomes in this high-risk population.

Differences in postoperative prognosis between early-stage lung adenocarcinoma and squamous cell carcinoma.

Although prognosis and treatments differ between small-cell- and nonsmall-cell carcinoma, comparisons of the histological types of NSCLC are uncommon. Thus, we investigated the oncological factors associated with the prognosis of early-stage adenocarcinoma and squamous cell carcinoma. We retrospectively compared the clinicopathological backgrounds and postoperative outcomes of patients diagnosed with pathological stage I-IIA adenocarcinoma and squamous cell carcinoma primary lung cancer completely resected at our department from January 2007 to December 2017. Multivariable Cox regression analysis for overall survival and recurrence-free survival was performed. The median follow-up duration was 55.2months. The cohort consisted of 532 adenocarcinoma and 96 squamous cell carcinoma patients. A significant difference in survival was observed between the two groups, with a 5-year overall survival rate of 90% (95% confidence interval 86-92%) for adenocarcinoma and 77% (95% CI 66-85%) for squamous cell carcinoma (P<0.01) patients. Squamous cell carcinoma patients had worse outcomes compared to adenocarcinoma patients in stage IA disease, but there were no significant differences between the two groups in stage IB or IIA disease. In multivariate analysis, invasion diameter was associated with overall survival in adenocarcinoma (hazard ratio 1.76, 95% confidence interval 1.36-2.28), but there was no such association in squamous cell carcinoma (hazard ratio 0.73, 95% confidence interval 0.45-1.14). The importance of tumor invasion diameter in postoperative outcomes was different between adenocarcinoma and squamous cell carcinoma. Thus, it is important to consider that nonsmall-cell carcinoma may have different prognoses depending on the histological type, even for the same stage.

Reproductive and Oncologic Outcomes in Young Women with Stage IA and Grade 2 Endometrial Carcinoma Undergoing Fertility-Sparing Treatment: A Systematic Review.

Endometrial cancer (EC) is the most common gynecological malignancy in both Europe and the USA. Approximately 3-5% of cases occur in women of reproductive age. Fertility-sparing treatment (FST) options are available, but very limited evidence regarding grade 2 (G2) ECs exists in the current literature. This systematic review aimed to comprehensively evaluate reproductive and oncologic outcomes among young women diagnosed with stage IA or G2EC disease who underwent FST. A comprehensive search of the literature was carried out on the following databases: MEDLINE, EMBASE, Global Health, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register), the Health Technology Assessment Database, and Web of Science. Only original studies that reported the oncologic and reproductive outcomes of patients with stage IA and G2EC tumors who underwent FST were considered eligible for inclusion in this systematic review (CRD42023484892). Studies describing only the FST for endometrial hyperplasia or G1 EC were excluded. Twenty-two papers that met the abovementioned inclusion criteria were included in the present systematic review. Preliminary analysis suggested encouraging oncologic and reproductive outcomes after FST. The FST approach may represent a feasible and safe option for women of childbearing age diagnosed with G2EC. Despite these promising findings, cautious interpretation is warranted due to inherent limitations, including heterogeneity in study designs and potential biases. Further research with standardized methodologies and larger sample sizes is imperative for obtaining more robust conclusions.

Preliminary study on implementation of modified tubular gastric side-overlap anastomosis in laparoscopic proximal gastrectomy

Objective: To investigate the feasibility and safety of implementing modified tubular gastric side-overlap anastomosis in laparoscopic proximal gastrectomy. Methods: In this retrospective, descriptive case series, we analyzed clinical data of seven patients who had undergone laparoscopic proximal gastrectomy and gastrointestinal reconstruction with modified tubular gastric side-overlap anastomosis from October 2022 to March 2023 in the Second Affiliated Hospital of Fujian Medical University. The study patients comprised five men and two women aged 57-72 years and of body mass index 18.5-25.7 kg/m2. All seven patients had preoperative gastroscopic and pathological evidence of esophagogastric junction cancer and all were found by preoperative enhanced computed tomography and/or endoscopic ultrasonography to have stage CT1-2N0M0 tumors. The main steps in the reconstruction of a modified tubular gastric side-overlap anastomosis are as follows: (1) mobilizing the lower esophagus and opening the left pleura to expand the space; (2) severing the esophagus with a linear cutter stapler; (3) creating a 3-cm-wide tubular stomach along the greater curvature; (4) creating a 5-cm guide line on the lesser curvature of the anterior wall of the tubular stomach and a small opening below the guide line; (5) rotating the esophageal stump 90° counterclockwise and making a small opening on the right posterior wall of the esophageal stump, along with using a 45-mm linear cutter stapler for esophagogastric side-to-side anastomosis under the guidance of the gastric tube and guide line ; (6) closing the common opening using barbed sutures; (7) embedding the cut edge of the esophageal stump such as to closely oppose it to the esophagus; (8) using barbed sutures to continuously suture the lower esophagus bilaterally to the anterior wall of the tubular stomach; and (9) closing the opened esophageal hiatus and pleura. The main outcome measures were intraoperative (operation time, digestive tract reconstruction time, closing the common opening time, intraoperative blood loss, and number of dissected lymph nodes), postoperative (time to passage of flatus , time to liquid diet, time to ambulation, length of postoperative hospital stay, and postoperative complications), pathological (maximum diameter of the tumor and pathological stage) and findings on follow-up. Results: Laparoscopic proximal gastrectomy with reconstruction of a modified tubular gastric side-overlap anastomosis was successfully completed in all seven patients; no conversion to laparotomy was required and there were no postoperative complications. The operation time, digestive tract reconstruction time, and closing of common opening time were 187-229, 61-79, and 7-9 minutes, respectively. Intraoperative blood loss was 15-23 ml and the number of dissected lymph nodes was 14-46 per case. Time to passage of flatus, time to liquid diet, time to ambulation, and postoperative hospital stay were 1-2, 2-3, 3-4, and 6-7 days, respectively. Postoperative pathological examination showed that the maximum tumor diameters were 1.6-3.3 cm in four patients with stage IA disease and three patients with stage IB. The seven patients were followed up for 6-11 months, during which none required routine use of proton pump inhibitors or gastric mucosal protective agents and there were no deaths or tumor recurrence/metastasis. No patients had anemia or hypoproteinemia 3 and 6 months after surgery. Six months after surgery, NRS2002 and GERDQ scores were 1-2 and 2-3, respectively. Gastroscopy showed narrow anastomoses in 6 patients with Los Angeles grade A and one patient with grade B disease. No evidence of significant bile reflux was found and no anastomotic stenosis or reflux was detected on upper gastrointestinal angiography. Conclusion: It is safe and feasible to implement modified tubular gastric side-overlap anastomosis for digestive tract reconstruction in laparoscopic proximal gastrectomy.

The role of pre-operative ctDNA in resectable intrahepatic cholangiocarcinoma.

528 Background: Genomic profiling of circulating tumor DNA (ctDNA) is increasingly used in intrahepatic cholangiocarcinoma (iCCA) to inform precision oncology approaches and determine resistance mechanisms to targeted therapies. The application of pre-operative ctDNA testing in the management of iCCA for prognostication remains unclear. Methods: In this retrospective study, we analyzed pre-operative plasma samples from 14 patients who underwent curative resection for iCCA without neoadjuvant therapy. A personalized and tumor-informed assay (Signatera; Natera, Inc.) was used for the detection and quantification of ctDNA. We correlated ctDNA profiles with baseline tumour characteristics and clinical outcomes. Results: The mean interval between pre-operative blood collection and surgery was 43 days (range: 1 to 90 days). ctDNA was detected in all patients except for one with stage Ia (AJCC 8th) disease (Table). The mean pre-operative ctDNA concentration was lowest in the stage Ia group [4.2 mean tumor molecules (MTM)/mL] and highest in the stage II group (134.0 MTM/mL). The mean pre-operative ctDNA concentration did not exhibit a linear correlation with disease recurrence or mortality rates, however, it showed a moderate-to-good linear correlation with the largest pathologic tumor size (R2 = 0.55). Among the three patients who had IDH1/2 mutations tracked in the plasma by Signatera, two patients had positive IDH1/2 detection in ctDNA with mean ctDNA concentrations of 83.7 MTM/mL (range: 33.8 to 133.5 MTM/mL). The patient with the second-highest ctDNA concentration (133.5 MTM/mL and 1818 days follow-up) had stage Ib disease with an IDH1 mutation but has shown no evidence of recurrence. Conclusions: In the pre-operative setting for iCCA resections, ctDNA can be reliably detected across all disease stages using a tumor-informed approach, even when blood is collected up to 90 days before surgery. While single time-point pre-operative ctDNA concentration levels do not appear to correlate with outcomes, similar to previous reports in colon adenocarcinoma, they may correlate with tumor volume. Further studies are needed to evaluate the utility of tumor-informed ctDNA testing in the post-operative setting to detect molecular residual disease for improved prognostication. [Table: see text]

Sex-specificity in Surgical Stages of Lung Cancer in Young Adults.

Young Patients with lung cancer represent a distinct subset of patients with this neoplasm. Young International studies show increased lung cancer rates in females, while the incidence in males continues to decline. There is evidence to suggest that this trend recurs in younger patients. We studied the effects of gender differences on the incidence of surgical stages of lung cancer in young adults and its mortality rate. This study is a retrospective review (2010-2020) of young adults (aged under 45 years) with surgical-stage of lung cancer. We calculated female-to-male differences in incidence rate ratios, tumor characteristics, surgical management, and survival. Cumulative survival curves were generated by the Kaplan-Meier method. We examined 46 men and 24 women, under 45 years. Female patients were diagnosed at earlier stages. The proportion of stage IA disease was significantly higher in women than in men (46% versus 13%, respectively) (p=0.03). Women were more likely never smokers (42% versus 83%, p=0.02). A histologic subtype, females were more likely to have typical carcinoid tumors (13.54% versus 10.21% for males) (p>0.05). The largest histological type in men was adenocarcinoma (25.53% versus 4.16%, p>0.05). All the patients were operated. Three men had neoadjuvant chemotherapy and one was operated on for cerebral oligometastatic before his chest surgery. Adjuvant chemotherapy was given to 7 women and 21 men. Despite the small number of postoperative complications in our study (n= 8, 11.2%), the male sex was significant in predicting this complication (p<0.05). The mortality rate was 1.4%. The 5-year overall survival rates were 84% in men and 87% in women. Our study identified sex differences in the incidence and mortality rates for surgical lung cancers in young adults, but the biological and endocrine mechanisms implicated in these disparities have not yet been determined.

Impact of CT-guided hookwire localization on tumor spread through air spaces in stage IA lung adenocarcinoma

BackgroundIt remains undetermined whether preoperative computed tomography (CT)-guided hookwire localization would result in elevated risk of tumor spread through air spaces (STAS) in stage IA lung adenocarcinoma. MethodsA total of 1836 patients who underwent lobectomy were included. To eliminate the potential impact of confounding factors on producing STAS, propensity score–matching (PSM) was used to create two balanced subgroups stratified by implementation of hookwire localization. We also introduced an external cohort including 1486 patients to explore the effect of hookwire localization on the incidence of STAS and patient survival after sublobar resection (SR). For proactive simulation of hookwire localization, 20 consecutive lobectomy specimens of p-stage IA lung adenocarcinoma were selected. ResultsEx vivo tests revealed that mechanical artifacts presenting as spreading through a localizer surface (STALS) could be induced by hookwire localization but be distinguished by CD68 and AE1/3 antibody-based immunohistochemistry. The distance of STALS dissemination tended to be shorter compared with real STAS (P = 0.000). After PSM, implementation of hookwire localization was not associated with elevated STAS incidence, nor worse survival in p-stage IA patients undergoing lobectomy irrespective of STAS. ConclusionsCT-guided hookwire localization might induce mechanical artifacts presenting as STALS which could be distinguished by immunohistochemistry, but would not affect survival in p-stage IA disease. Surgeons can be less apprehensive about performing hookwire localization in relation to STAS on stage IA disease suitable for SR.

Operative outcomes and middle-term survival of robotic-assisted lung resection for clinical stage IA lung cancer compared with video-assisted thoracoscopic surgery

BackgroundDespite limited published evidence, robotic-assisted thoracoscopic surgery (RATS) for anatomic lung resection in early-stage lung cancer continues growing. The aim of this study is to evaluate its safety and oncologic efficacy compared to video-assisted thoracoscopic surgery (VATS). MethodsSingle-centre retrospective study of all patients with resected clinical stage IA NSCLC who underwent RATS or VATS anatomic lung resection from June 2018 to January 2022. RATS and VATS cases were matched by propensity scoring (PSM) according to age, sex, histology, and type of resection. Short-term outcomes were compared, and the Kaplan-Meier method and log-rank test were used to evaluate the overall survival (OS) and disease-free survival (DFS). Results321 patients (94 RATS and 227 VATS cases) were included. After PSM, 94 VATS and 94 RATS cases were compared. Demographics, pulmonary function, and comorbidity were similar in both groups. Overall postoperative morbidity was comparable for RATS and VATS cases (20.2% vs 25.5%, P = 0.385, respectively). Pathological nodal upstaging was similar in both groups (10.6% in RATS and 12.8% in VATS). During the 3.5-year follow-up period (median: 29 months; IQR: 18–39), recurrence rate was 6.4% in RATS group and 18.1% in the VATS group (P = 0.014). OS and DFS were similar in RATS and VATS groups (log rank P = 0.848 and P = 0.117, respectively). ConclusionRATS can be performed safely in patients with early-stage NSCLC. For clinical stage IA disease, robotic anatomic lung resection offers better oncologic outcomes in terms of recurrence, although there are no differences in OS and DFS compared with VATS.

A Case for the Conservative Management of Stage IA Cervical Cancer.

Cervical cancer remains a significant public health concern within the United States and across the world. Cervical cancer is most frequently diagnosed in women between the ages of 35 and 44 and therefore affects a younger patient population than many other cancers. The management of early-stage disease has frequently utilized radical hysterectomy with the associated increased surgical morbidity, without clear evidence of any benefits. In stage IA disease, there are retrospective pathologic data supporting the safety of conservative surgery and lymphadenectomy over radical hysterectomy. There are also emerging prospective studies supporting conservative management. This editorial presents the evidence for conservative management of stage IA cervical cancer by reviewing the existing retrospective studies as well as the ongoing prospective studies.

Low Dose Involved Site Radiotherapy as Single Modality Treatment for Early-Stage Nodular Lymphocyte Predominant Hodgkin Lymphoma.

Involved site radiotherapy as a single modality is considered standard of care for early-stage non-bulky nodular lymphocyte predominant Hodgkin's Lymphoma (NLPHL) with excellent rates of local control and overall survival. Guidelines suggest a dose of 30 Gy in conventional fractionation, however NLPHL has an indolent course and clinically behaves likes a low-grade lymphoma. Given the good prognosis NLPHL has been treated as low grade non-Hodgkin's lymphoma with a dose of 24 Gy in 12 fractions. Eleven patients with stage I-II non-bulky NLPHL treated with involved site radiotherapy alone to a dose of 24 Gy in 12 fractions between 2010 and 2021 were respectively identified and reviewed. Data on toxicity, post treatment PET, relapse and site of relapse were recorded from multidisciplinary meetings records and regular six monthly clinic reviews. Mean patient age was 45 (range 25-74), 9 were male. 8 were classified as having Ann-Arbor stage IA disease, and the remaining 3 had IIA disease. All patients were prescribed 24 Gy in 12 fractions, 6 patients had 3D-conformal radiotherapy, 1 static IMRT and 4 VMAT. After a median follow up of 32 months (range 12-147) the overall response rate was 100% and all patients had complete metabolic response on PET scan, performed three months following the completion of radiotherapy. All patients remained disease free throughout the follow up period (PFS and OS 100%). There were no late toxicities reported. This is the largest reported series of NLPHL patients treated with low dose involved site modern radiotherapy. Patients had excellent local control rates and survival with no significant toxicity, supporting the use of 24 Gy in early-stage non-bulky disease.

Single Institute Experience Treating Uterine Carcinosarcoma: Outcome Analysis

Uterine carcinosarcoma (UCS) is rare with a poor prognosis. We report over 10 years' experience, reporting prognostic and predictive factors for overall survival (OS) and disease-free survival (DFS). Patient, tumor, treatment and relapse characteristics of 168 women with stages I-IVB UCS treated at our institute between 2010 and 2020 were analyzed. OS and DFS at 2 and 5 years were the primary outcomes, estimated with Kaplan-Meier. The benefit of adjuvant chemotherapy and radiotherapy in the curative cohort was estimated using the log rank test. Median follow up was 23 months (range 1-137 months). 34% had FIGO stage IA disease, 10% IB, 8% II. 16% IIIA-IIIC1, and 10% IIIC2 and 22% IVB. The overall 2-year OS was 52% and 5-year OS 30%. 2-year OS by FIGO stage were: IA 66%; IB 63%; II 54%; IIIA-IIIC1 54%; IIIC2 45%; IVB 26%. Within the curative cohort who were surgically staged, 2-year DFS was 47% and 5-year was 30%. 2-year DFS were 61% in IA disease, 53% IB, 12% II, 51% IIIA-IIIC1, and 45% IIIC2 and 4% IVB. A greater risk of death was conferred by lack of adjuvant treatment (lack of chemo > lack of radiotherapy). The most common chemotherapy regimen used was Carboplatin Paclitaxel and pelvic radiotherapy 45Gy 25F over 5 weeks. The combination of surgery and chemotherapy +/- radiotherapy significantly improved OS compared to surgery +/- radiotherapy (HR 0.5 with CI 0.3 - 0.9) p<0.05. Radiotherapy improved OS compared to surgery only (HR 0.4 with CI 0.2 - 1.1) p<0.05. Relapse rate in all patients following curative treatment is 72% within year 1 and 86% within year 2 from diagnosis. In 52 patients with stage 1A disease treated with surgery +/- radiotherapy only, 42.4% relapsed, median time to relapse was 8 months from diagnosis. Relapse occurred despite 69.2 % stage 1A patients receiving adjuvant pelvic EBRT and in these patients relapse within the pelvis occurred in 50%. This study constitutes the largest retrospective analyses of long-term mortality outcomes in UCS and confirms poor outcomes despite curative surgery and adjuvant therapy. Most patients relapse within the first year following curative treatment. The use of adjuvant chemotherapy improves OS in all stages. In stage 1A disease 42 % patients relapse locally and distantly. This is an area of controversy and this data would strongly suggest that the addition of adjuvant paclitaxel-carboplatin or cisplatin-doxorubicin chemotherapy to EBRT should be considered in all patients including earliest stage disease.

Paediatric Mycosis Fungoides: Clinical Variants, Treatment Modalities and Response to Therapy.

Mycosis fungoides is a rare cutaneous lymphoma in the paediatric population. The aim of this study was to examine the epidemiological, clinical, and histological characteristics, as well as the treatment modalities and response to therapy of paediatric patients with mycosis fungoides. This retrospective cohort study reviewed the records of 37 paediatric patients treated at Rambam Medical Center, Israel, between 2013 and 2021. Extracted data included epidemiology, clinical presentation, histological reports, infiltrate clonality status, treatment modalities and response to therapy. The mean follow-up period was 60 months. All patients were diagnosed with stage IA or IB disease. Folliculotropic mycosis fungoides was the most prevalent variant (49%). Most patients were treated with phototherapy (90%), with a response rate of 85%, and a complete response rate of 55% after the first course. There were no significant differences in response to phototherapy between the folliculotropic or other variants (p = 0.072). Similarly, delayed diagnosis, atopic diathesis, clonality, phototherapy type or number of treatments, were not associated with response to therapy, while protracted phototherapy was associated with prolonged remission. In conclusion, mycosis fungoides in the paediatric population is an indolent disease with a favourable prognosis and potentially prolonged response to phototherapy.

Prediction model on disease recurrence for low risk resected stage I lung adenocarcinoma.

Although stage I non-small cell lung carcinoma (NSCLC) typically carries a good prognosis following complete resection, early disease recurrence can occur. An accurate survival prediction model would help refine a follow-up strategy and personalize future adjuvant therapy. We developed a post-operative prediction model based on readily available clinical information for patients with stage I adenocarcinoma. We retrospectively studied the disease-free survival (DFS) of 408 patients with pathologically confirmed low-risk stage I adenocarcinoma of lung who underwent curative resection from 2013 to 2017. A tree-based method was employed to partition the cohort into subgroups with distinct DFS outcome and stepwise risk ratio. These covariates were included in multivariate analysis to build a scoring system to predict disease recurrence. The model was subsequently validated using a 2011-2012 cohort. Non-smoker status, stage IA disease, epidermal-growth factor receptor mutants and female gender were associated with better DFS. Multivariate analysis identified smoking status, disease stage and gender as factors necessary for the scoring system and yielded 3 distinct risk groups for DFS [99.4 (95% CI 78.3-125.3), 62.9 (95% CI 48.2-82.0), 33.7 (95% CI 24.6-46.1) months, p < 0.005]. External validation yielded an area under the curve by receiver operating characteristic analysis of 0.863 (95% CI 0.755-0.972). The model could categorize post-operative patients using readily available clinical information, and may help personalize a follow-up strategy and future adjuvant therapy.

Role of Rituximab Addition to First-line Chemotherapy Regimens in Nodular Lymphocyte-predominant Hodgkin Lymphoma: A Study by Fondazione Italiana Linfomi.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare entity whose neoplastic cells retain a B-cell phenotype with expression of CD20. Radiotherapy is recommended for favorable stage IA disease while for other stages guidelines suggest therapeutic strategies similar to those used for classic HL. The role of rituximab, although quite widespread, is not completely elucidated. We retrospectively analyzed baseline characteristics of 308 consecutive patients with NLPHL diagnosed in 19 Italian centers from 2000 to 2018. With a median follow-up of 8.4 years (interquartile range: 4.5-12.4) for treated patients, median overall survival (OS) was not reached and estimated 5-year OS was 97.8% and 5-year progression-free survival (PFS) was 84.5%. Five-year cumulative incidence of histological transformation was 1.4%, 95% confidence interval (CI), 0.5%-3.8%. After adjusting for lymphocyte count, splenic involvement, bulky disease and B symptoms (fever, drenching night sweats, unintentional loss >10% of body weight within the preceding 6 months), patients with stage II or more showed superior PFS with immunochemotherapy in comparison to chemotherapy alone (hazard ratio = 0.4, 95% CI, 0.2-0.8; P = 0.015). Our data suggest an advantage of the use of rituximab combined with chemotherapy ± radiotherapy in the treatment of stage II-III-IV NLPHL.

Impact of surgery and adjuvant chemotherapy on the survival of stage I lung adenocarcinoma patients with tumor spread through air spaces

ObjectivesTumor spread through air spaces (STAS) is a unique mechanism of lung cancer metastasis; however, its clinical value for stage I lung adenocarcinoma (ADC) remains unclear at present. We investigated the (1) prognosis of patients after sublobar resection compared with lobectomy for stage I lung adenocarcinoma with STAS; and (2) potential benefits of adjuvant chemotherapy (ACT) for patients with stage I ADC and STAS. MethodsA total of 3328 consecutive patients with stage I ADC were retrospectively identified between 2014 and 2018 at our institution; among them, 600 were diagnosed with STAS. Kaplan–Meier analysis and Cox proportional hazard regression models were used to evaluate the impact of STAS on overall survival (OS) and recurrence-free survival (RFS). ResultsAmong stage IA patients with STAS, there was no significant difference between those who underwent sublobar resection and lobectomy in OS (P = 0.919) and RFS (P = 0.066). Multivariate analysis confirmed this result (sublobar resection versus lobectomy, OS: HR = 0.523, 95 % CI, 0.056–18.458, P = 0.714; RFS, HR = 0.360, 95 % CI, 0.115–1.565, P = 0.897). ACT did not improve the prognosis of stage IA patients but did improve the RFS of stage IB patients with high-risk recurrence factors, including poorly differentiated tumors, lymphovascular invasion and visceral pleural invasion (P = 0.046). ConclusionsSublobar and lobectomy resection provided a comparable prognosis for stage IA ADC patients with STAS. When STAS was confirmed postoperatively, ACT should be considered for patients with stage IB with high-risk recurrence factors but not for those with stage IA disease.

Ultrasonography, macroscopy, and frozen section: whıch is better for predicting deep myometrial invasıon in endometrial cancer?

The aim of this study was to compare the power of preoperative transvaginal ultrasonography, intraoperative macroscopic examination, and frozen section for predicting deep myometrial invasion in endometrial cancer. This is a retrospective review involving 68 patients who underwent surgical staging for endometrial cancer from 2014 to 2017. Patients with grade 3 endometrial cancer and non-endometrioid tumors were excluded. The findings related to preoperative transvaginal ultrasonography, intraoperative macroscopic examination, and frozen section were compared with definitive histopathological diagnosis. The mean age, gravidity, and body mass index of the patients were 58.1±8.9 years (range: 30-80 years), 3.2±2.1 (range: 0-9), and 33.5±6.6 kg/m2 (range: 20-52 kg/m2), respectively. Only 11 (16.2%) patients were in the premenopausal period, while 57 (83.8%) were in the postmenopausal period. Grade 1 endometrial cancer was found in 29 patients (42.6%) and grade 2 tumors were specified in 39 patients (57.4%). Stage IA disease was found in 45 (66.2%) patients, while stage IB disease was observed in 23 (33.8%) patients. The 5-year survival rate was 91.2%. The sensitivity of preoperative transvaginal ultrasonography, intraoperative macroscopic examination, and frozen section were 56, 34, and 52%, respectively, for predicting deep myometrial invasion. In contrast, the specificity of preoperative ultrasonography, intraoperative macroscopic examination, and frozen section were 86, 100, and 100%, respectively. Transvaginal ultrasonography and intraoperative frozen section were found to have similar sensitivity and specificity for predicting deep myometrial invasion. Preoperative transvaginal ultrasonography appears as an efficient approach for predicting endometrial cancers with deep myometrial invasion.

Uterine Rupture in Nulliparous Woman Without Risk Factors: A Case Report and Literature Review

Objective: The aim of this study was to summarize the main features of spontaneous uterine rupture in primigravid patients before the onset of labor, emphasize the possibilities of therapeutic conduct, and offer points of reflection on the post-rupture management. Methods: We performed a literature review of all the individual case reports, retrospective case series, and reviews concerning uterine rupture in peer-reviewed journals from January 1975 to October 2021. Result: The diagnosis of uterine rupture was commonly made by abdominal pain, with or without concomitant nausea and vomiting. Uterine ruptures occur more frequently at the end of pregnancy or in the third trimester. The most frequently involved site is the uterine cornua followed by the posterior wall of the uterus. Other described cases identify the broad ligament, uterus sacral ligament, lower uterine segment, and anterior wall as possible points of rupture. The most frequently used suturing technique is the repair of the breach in two layers. Conclusion: Uterine rupture is an extremely rare obstetric emergency, correlated to life-threatening consequences for both the newborn and the woman. Considering the maternal and fetal risks, a tempestive diagnosis is mandatory.

Diagnostic Accuracy in the Detection of Depth of Myometrial Invasion with MRI in Early-Stage Endometrial Cancer

Objective: To study the diagnostic accuracy of pre-operative magnetic resonance imaging (MRI) in early-stage endometrial cancer with postoperative International Federation of Gynecology and Obstetrics (FIGO) staging after comprehensive staging surgery. Methods: Retrospectively, the medical records of 78 patients with early-stage endometrial cancer were analysed for the involvement of the myometrium with the tumour by diagnostic MRI and compared with histopathological reports after surgical staging. Results: The median age of patients was 56 years (ranging from 32 to 73). The median body mass index (BMI) of these women was 29 (ranging from 20 to 40). On histopathology, 72 women (92.3%) had type I endometroid endometrial cancer and 6 (7.7%) had type II carcinoma; four had papillary serous carcinoma, one had clear cell carcinoma and one had undifferentiated carcinoma. However, 43 (55.1%) had a grade I tumour, 12 (15.1%) had a grade II tumour and 17 (21.6%) had a grade III tumour. Further, 35 (44.8%) were staged laparoscopically, and 43 (55.1%) underwent open staging laparotomies. Pre-operative MRI radiological staging was carried out on all patients before surgery. However, 52 (66.7%) had stage IA disease, which suggested less than half of myometrial infiltration by tumour. Further, 21 (26.9%) showed more than half myometrial infiltration stage IB. One (1.2%) patient had stage IIIC1 disease with pelvic nodes of 2.5 × 2 cm near the obturator fossa; one (1.2%) patient had retroperitoneal nodes and para-aortic nodes of the largest 2 × 2 cm; three patients (3.8%) showed involvement of the endocervix with the tumour. Patients were histopathologically staged postoperatively according to the FIGO classification following complete staging surgery. Further, 46 (59%) were stage IA, 26 (33.3%) were stage IB, 3 (3.8%) showed stage II and 3 (3.8%) had stage IIIC1. The sensitivity for MRI for stage IA was 95.65% with (85% to 99.4%) 95% CI. The specificity was 75%, with 56.6% to 88.55 of the 95% CI. The positive likelihood ratio was 3.83, with a 95% confidence interval of 2.09 to 6.99. The sensitivity of MRI for stage IB was 69.23%, ranging from 48.2% to 85.6% of the 95% CI. The specificity was 94.23%, with 84% to 98% of the 95% CI. The positive likelihood ratio was 12, with a 95% confidence interval of 3.8 to 37. Conclusion: A pre-operative MRI contributes to the accurate staging of endometrial cancer to allow planning for the scale of the surgery. This is important for pre-operative counselling. The depth of myometrial infiltration aids in the planning of pelvic and para-aortic lymphadenectomy. Our study is comparable with the results of previous studies.