Stage IA Tumors Research Articles

Video-assisted thoracoscopic trisegmentectomy and left upper lobectomy provide equivalent survivals for stage IA and IB lung cancer

Despite a trend toward sublobar resections for lung cancers, some question the adequacy of limited resections in the treatment of lung cancer and questions remain about performing these procedures by video-assisted thoracoscopic surgery (VATS). We compared the survival for lung cancers treated with VATS segmentectomy versus VATS lobectomy. VATS segmentectomy and lobectomy for both malignant and benign lung pathology are reviewed from a single institution. Between 1998 and 2010, 73 VATS trisegmentectomies were performed in 49 women and 24 men (mean age, 72 years). Diagnoses included primary lung cancer (91%), benign disease (4%), and metastatic disease (5%). Primary lung cancers were 68% for stage IA, 17% for stage IB, and 15% for stage II-IV. Seventy-three left upper lobe (LUL) trisegmentectomies were performed. Mean hospital stay after VATS trisegmentectomy was 3.8 days, versus 5.5 days after VATS LUL lobectomy (P = .0736). Complication rates for trisegmentectomy group (37%) and lobectomy (17%; P > .05) were not statistically different. Survival after VATS trisegmentectomy and LUL lobectomy for either stage IA lung cancer or stage IB lung cancer was not statistically significant. Segmentectomy can be performed by VATS with no greater morbidity and mortality than with VATS lobectomy. LUL trisegmentectomy provides the same survival as lobectomy for stage IA and IB tumors. Our experience supports the use of lingular-sparing trisegmentectomy in the treatment of stage IA and IB lung cancer.

Clinical significance of GADD153 expression in stage I non-small cell lung cancer

The transcription factor growth arrest and DNA damage-inducible gene 153 (GADD153), also known as CHOP, is considered to function as a proapoptotic molecule. Overexpression of GADD153 leads to cell cycle arrest and/or apoptosis. However, its clinical implications in non-small cell lung cancer (NSCLC) remain controversial. Therefore, we investigated the expression of GADD153 in stage I NSCLC using immunohistochemistry. Paraffin-embedded tissue sections from 76 patients, who were diagnosed with primary stage I NSCLC and had undergone a curative lung resection, were stained using an anti-GADD153 antibody. The intensity of GADD153 immunostaining was evaluated within the cell membrane and cytoplasm of invasive cancer components. The correlation between the intratumoral expression of GADD153 and various clinical parameters were explored. GADD153 was detected in 29 (38.2%) cases. No statistically significant difference in expression was demonstrated between stage IA and stage IB tumors (35.0 vs. 39.3%; P=0.735). The expression of GADD153 was not affected by histological subtypes or histological grades of differentiation. The intratumoral expression of GADD153 did not influence the overall survival rate (53.29 vs. 52.18 months; P=0.743) or disease-free survival rate (46.97 vs. 54.19 months; P=0.084) of stage I NSCLC patients. However, patients with GADD153 expression demonstrated an improved disease-specific survival rate (28.80 vs. 53.85 months; P=0.020). No patients with GADD153 expression demonstrated distant metastasis (P=0.029). These data suggest that GADD153 expression may be a valuable prognostic factor of early-stage NSCLC in patients who have undergone curative lung resection.

Abstract 4937: Factors in NSCLC stage and outcome: Integrated genome-wide study

Abstract Genome wide data has transformed disease diagnostic and prognostic model development through the identification of molecular profiles. Enhanced molecular insight can be achieved by multiple -omic profile integration. Accordingly, we used a novel multistep integrative unsupervised approach, the network phenotyping strategy (NPS), for discovery of disease diagnostic/prognostic panels in resected NSCLC frozen tumor samples (n=81; 29 Stage IA/52 Stage IB). Whole genome gene expression and DNA methylation data was generated using Illumina BeadChips. In NPS step 1, the most common (>18% of the cohort) hypo- and hyper-methylated genes (lowest/highest β-score; n=31) were identified. In step 2, a subset of these genes was found to reside in networked multiple loci, co-protected against genetic variation by extreme (high n=10 or low n=6) incorporation energy costs, based on an exome entromic analysis. In step 3, maximal spanning tree reduction of a network of all 120 possible expression level relationships for these 16 genes, weighted by the correlation coefficients quantifying co-regulation, was used to identify the most informative sub-network, an 8-partite graph K8. For each partition, cases were dichotomized into groups where gene 1 was expressed at least 1.5x higher or lower relative to gene 2. In step 4, K8 cycle-decomposition revealed only 8 distinct gene expression patterns (C1-C8) representing nominally different molecular NSCLC subtypes. Characterization of individual tumor expression patterns was computed as the patient's difference vector (ΔC) from C1-C8. Stage IA tumor gene expression patterns (overexpression of all 16 genes) most closely matched C1 (true positive rates 0.8 - 0.93 and false positive rates 0.2 - 0.07, ROC 0.9 in 10-fold cross-validation). For stage IB, these 16 gene expression levels were lower and heterogeneous. In step 5, we generated OS prediction models. The ΔCs were used in an alternating decision tree algorithm. Two rule sets were found, one for the high gene expression Stage IA tumors and the second for Stage IB. In a 10-fold cross-validation, the log-rank test for equality of survivor functions resulted in optimal OS separation at 1650 days (p<0.0005). These results demonstrate that: 1) graph theory provides tools for handling complex data relationships without loss of analytic power; and 2) networks of genome loci co-protected against variant incorporation form a filter identifying the function in experimental -omic data. Here, the 16 gene panel we identified includes members of 3 common lung tumorigenesis pathways and/or were co-regulated by miRNAs independently found to be associated with prognosis in our cohort. The integrative NPS facilitated the epigenetic identification of a biomarker gene set, stage classification by overall expression levels and disease outcome prediction by the expression patterns captured by C1-C8. Supported in part by NIH 5P50 CA090440, P30 CA047904, UPMC Institutional Funds. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4937. doi:1538-7445.AM2012-4937

Influence of Cigarette Smoking on Survival and Tumor Invasiveness in Clinical Stage IA Lung Adenocarcinoma

The objective of this study was to investigate the association between cigarette smoking, cancer survival, and pathological features of clinical stage IA lung adenocarcinoma. Between August 1992 and December 2007, 1,070 consecutive patients with clinical stage IA lung adenocarcinoma underwent complete resection with systematic lymph node dissection. Univariate analysis by log-rank tests was performed to determine unfavorable prognostic factors, and the Cox proportional hazards regression model was used to identify the potential independent predictors. The overall 5-year survival rate of patients with greater than 20 pack-years (PY>20) was 71%, significantly lower than patients with 20 or less pack-years (PY≤20; 86%; p<0.001). Postoperative pathological prognostic factors, including moderate or poor histologic differentiation, lymphatic permeation, intratumoral vascular invasion, visceral pleural invasion, and lymph node metastasis, were detected more often in patients with greater than 20 PY. Sixty-five percent of the patients in this study had pathological stage IA tumors, and their overall 5-year survival rates with 20 or less PY and greater than 20 PY were 97% and 86%, respectively (p<0.001). In patients with clinical stage IA adenocarcinoma, a history of heavy smoking was associated with poor outcomes and was a statistically significant predictor of histologic tumor invasion.

Influence of Age and IB Status After Resection of Node-Negative Non-Small Cell Lung Cancer

Anatomic segmentectomy has been proposed as a reasonable alternative to lobectomy in the management of small early-stage non-small cell lung cancers. We reviewed our outcomes with anatomic segmentectomy versus lobectomy for stages IA and IB non-small cell lung cancer stratified by age and stage. We conducted a retrospective review of prospectively-collected data analyzing outcomes after anatomic segmentectomy (n=305) for stage IA (n=187) or IB (n=118) NSCLC from 1999 to 2010. Lobectomy was performed in 594 patients for stage IA (n=290) and IB (n=304) disease during the same period. Surgical approach was stratified by stage and by the following age groups: less than 70, 70 to 79, and 80 or greater. Primary outcome variables included complications, mortality, recurrence patterns, and survival. Mean follow-up was 37 months. Segmentectomy was associated with reduced complications (43.6% vs 58.7%) and mortality (0% vs 7.8%) in patients greater than 80 years old, without a difference in recurrence rates. There was no difference in complications or mortality in the younger age groups. Freedom from recurrence was similar between segmentectomy and lobectomy for stage IA tumors across all age groups. A reduced recurrence-free survival was seen with segmentectomy for stage IB tumors, especially with visceral pleural invasion (median 22.7 vs 29.6 months), p=0.048). Segmentectomy appears to be a reasonable approach for early-stage NSCLC in patients 80 years of age or greater due to reduced morbidity and mortality with equivalent freedom from recurrence. Although equivalent survival was seen in all age groups for stage IA, these data further support the use of lobectomy for resection of stage IB tumors.

The incidence and clinical significance of lymph node micrometastases determined by immunohistochemical staining in stage I - lymph node negative endometrial cancer.

Determine the incidence and clinical relevance of lymph node micrometastases found with immunohistochemical (IHC) staining in patients diagnosed with stage I lymph node-negative endometrial adenocarcinoma. Eligible patients with endometrioid-type histology and negative lymph nodes by H&E were identified by a computerized database. After histologic confirmation, all paraffin-embedded pathologic specimens were freshly sliced and stained with IHC stains for pancytokeratin. Slides were interpreted by two pathologists and positive IHC staining for micrometastases was defined as positive staining of cells <2 mm in greatest dimension. Patient demographics, clinicopathologic factors, and follow-up data were abstracted. Fifty-one patients were included in our study. Most patients had stage IA (84%) tumors of grade 2/3 histology (51%), and 11 patients (22%) received adjuvant therapy. Mean number of lymph nodes was 12.2 per patient. Of 151 lymph node paraffin blocks evaluated for pancytokeratin, only two (1.3%) had IHC-positive micrometastases. The two lymph node-positive results occurred in separate patients, leading to 3.9% of all patients in our cohort. Both micrometastatic lymph node-positive patients had adjuvant radiation therapy for uterine high-risk factors and are currently without evidence of disease at 15 and 16 months, respectively. Three lymph node-negative patients (6.1%) have developed recurrences within a median follow-up of 15 months. The incidence of IHC stain-positive micrometastases in H&E-negative lymph nodes is low in surgically staged endometrial cancer and does not justify routine IHC staining. Additionally, as little evidence exists to support the clinical significance of IHC-stained micrometastases in endometrial cancer, further study is warranted.

Long-Term Results of Radiofrequency Ablation Treatment of Stage I Non-small Cell Lung Cancer: A Prospective Intention-to-Treat Study

About one-fifth of patients with resectable non-small cell lung cancer (NSCLC) are unsuitable for surgical treatment. Radiofrequency ablation offers an alternative minimally invasive option. We report the result of an intention-to-treat study with long-term follow-up. From 2001 to 2009, we performed 80 percutaneous radiofrequency ablations of 59 stage I NSCLC in 57 inoperable patients. Two patients were treated for two separate lesions. The study group consisted of 45 males and 12 females, with mean age of 74 years (range, 40-88 years). All patients had pathological evidence of NSCLC, which was in stage IA in 44 cases and in stage IB in the other 15 cases. The mean size of the lesions was 2.6 cm (range, 1.1-5 cm). Fourteen lesions were retreated up to five times. The procedure was always performed under local anesthesia and conscious sedation. Most of the procedures were performed under computed tomography guidance, with nine under ultrasonography guidance. In all cases, the procedure was technically successful. No mortality was recorded, and major morbidity consisted of four cases of pneumothorax requiring pleural drainage. At a mean follow-up of 47 months, the complete response rate was 59.3% (stage Ia 65.9%, stage Ib 40%, p = 0.01), with a mean local recurrence interval of 25.9 months. Median overall survival and cancer-specific survival were 33.4 and 41.4 months, respectively. Cancer-specific actuarial survival was 89% at 1 year, 59% at 3 years, and 40% at 5 years. Radiofrequency ablation treatment of early-stage NSCLC seems to be a effective minimally invasive therapy even in the long-term period, particularly for stage Ia tumors.

Lymphadenectomy influences the utilization of adjuvant radiation treatment for endometrial cancer

We analyzed the effect of lymphadenectomy on the use of adjuvant radiation treatment for women with stage I-II endometrial cancer. Women with stage I-II endometrioid adenocarcinomas treated between 1988 and 2006 and recorded in the Surveillance, Epidemiology, and End Results database were identified. The influence of lymphadenectomy (LND) on receipt of external beam radiation and brachytherapy stratified was examined. We identified 58,776 women including 26,043 who underwent LND (44.3%). Among women younger than 60 years of age with stage IA (grades 1, 2, and 3) tumors, LND had no impact on the use of radiation. Patients with stage IB (grade 2 or 3) and stage IC (grade 1 or 2) tumors who underwent lymph node dissection were less likely to undergo external beam radiation and more likely to receive vaginal brachytherapy (P < .05 for all). Furthermore, the extent of lymphadenectomy influenced the receipt of radiation. Women who undergo lymphadenectomy are less likely to receive whole pelvic radiotherapy.

OC27.01: Grayscale and color Doppler ultrasound characteristics of endometrial cancer in relation to stage, grade and tumor size

To describe the gray-scale and vascular characteristic of endometrial cancer in relation to stage, grade and size using 2D/3D transvaginal ultrasound. Prospective multicenter study including 144 women with endometrial cancer undergoing transvaginal ultrasound prior to surgery. The sonographic characteristics assessed were: echogenicity, endometrial/myometrial border, fibroids, vascular pattern using 3D, color score, and tumor/uterus antero-posterior (AP) ratio. Histological assessment of tumor stage, grade, type, and growth pattern was performed. Hyper- or isoechoic tumors were more often seen in stage IA, whereas mixed or hypoechoic tumors were more often found in > stage IB (P = 0.003). Hyperechoic tumors were more common in grade 1–2 tumors, P = 0.02, and tumors with a tumor/uterine AP ratio of < 50% of the uterus P = 0.002, whereas non-hyperechoic appearance was more commonly found in grade 3 tumors and tumors with a tumor/uterine AP ratio > 50% of the uterus. Multiple global vessels were more often seen in > stage IB tumors than IA tumors P = 0.02, in grade 3 tumors than in grade 1 and 2 tumors P = 0.02, and in tumors with a tumor/uterine AP ratio > 50%, P < 0.001. A moderate/high color score was significantly more common in tumors of higher stage (P = 0.03) and greater size (P = 0.001). The sonographic appearance of endometrial cancer is significantly associated with tumor stage, grade and size. More advanced tumors often have a mixed/hypoechoic echogenicity, a higher color score and multiple globally entering vessels, whereas less advanced tumors are more often hyperechoic, and have no or low color score.

Gray‐scale and color Doppler ultrasound characteristics of endometrial cancer in relation to stage, grade and tumor size

To describe the gray-scale and vascular characteristics of endometrial cancer in relation to stage, grade and size using two-dimensional (2D)/three-dimensional (3D) transvaginal ultrasound. This was a prospective multicenter study including 144 women with endometrial cancer undergoing transvaginal ultrasound before surgery. The sonographic characteristics assessed were echogenicity, endometrial/myometrial border, fibroids, vascular pattern, color score and tumor/uterus anteroposterior (AP) ratio. Histological assessment of tumor stage, grade, type and growth pattern was performed. Hyperechoic or isoechoic tumors were more often seen in Stage IA cancer, whereas mixed or hypoechoic tumors were more often found in cancers of Stage IB or greater (P = 0.003). Hyperechogenicity was more common in Grade 1-2 tumors (i.e. well or moderately differentiated) (P = 0.02) and in tumors with a tumor/uterine AP ratio of < 50% (P = 0.002), whereas a non-hyperechoic appearance was more commonly found in Grade 3 tumors (i.e. poorly differentiated) and in tumors with a tumor/uterine AP ratio of ≥ 50%. Multiple global vessels were more often seen in tumors of Stage IB or greater than in Stage IA tumors (P = 0.02), in Grade 3 tumors than in Grade 1 and 2 tumors (P = 0.02) and in tumors with a tumor/uterine AP ratio of ≥ 50% (P < 0.001). A moderate/high color score was significantly more common in tumors of higher stage (P = 0.03) and larger size (P = 0.001). The sonographic appearance of endometrial cancer is significantly associated with tumor stage, grade and size. More advanced tumors often have a mixed/hypoechoic echogenicity, a higher color score and multiple globally entering vessels, whereas less advanced tumors are more often hyperechoic and have no or a low color score.

Efficacy of CT screening for lung cancer in never-smokers: Analysis of Japanese cases detected using a low-dose CT screen

CT-screening for lung cancer is fairly widely used for both smokers and never-smokers in East Asia because the mortality rate for never-smokers due to this cancer is relatively high in this region. We performed comparative analyses, as a retrospective study, on three lung cancer arms detected by CT-screen, X-ray-screen, and via analysis of clinicopathological features and outcomes in never-smokers from a symptomatic-prompted group of patients. The total study cohort comprised 218 patients in CT group, 160 in X-ray group, and 82 in symptomatic-prompted group. The percentage of bronchioloalveolar carcinoma (BAC) was 65.1% in CT-screen group. The ratio of stage IA tumors in CT-screen group was 88.5% and the ratio of advanced cases (i.e. stages IIIB+IV) was 2.3%. The 5-year-survival rates were 95.0% in CT-screen, 73.0% in X-ray-screen and 40.0% in symptomatic-prompted group. We performed further sub-analysis which excluded pure BACs (i.e. Noguchi types A and B) or pure GGOs within a 10mm diameter because this is indicative of a very favorable prognosis. Based on this sub-analysis the number of the subjects in each group became 76 in CT group; 140 in X-ray group and 77 in symptomatic-prompted group. The principal characteristics of the patients such as age and sex became almost even in the three arms. In CT-screen subgroup, the ratio of stage IA cancer was 69.7% and of advanced cases was 6.6%. This advanced ratio was lower than both X-ray-screen (22.1%) and symptomatic-prompted (61.9%) groups. The 5-year-survival rates were 89.9% among CT-screen group patients, 72.6% for X-ray screen cases and 39.1% in symptomatic-prompted group. A CT-screen was found to be one of the independent prognostic factors for lung cancer (HR, 0.28; 95% CI, 0.12–0.72) and based on this would be expected to reduce the risk of lung cancer death by 78% compared with non-screened cases. In conclusion, CT will improve the survival rate and decrease the rate of advanced cancers in never-smokers via the existing annual screening system. CT-screening is also an independent prognostic improvement factor in never-smokers, and will therefore reduce the risk of lung cancer death.

How close are we to customizing chemotherapy in early non-small cell lung cancer?

Although surgery is the only potentially curative treatment for early-stage non-small cell lung cancer (NSCLC), 5-year survival rates range from 77% for stage IA tumors to 23% in stage IIIA disease. Adjuvant chemotherapy has recently been established as a standard of care for resected stage II-III NSCLC, on the basis of large-scale clinical trials employing third-generation platinum-based regimens. As the overall absolute 5-year survival benefit from this approach does not exceed 5% and potential long-term complications are an issue of concern, the aim of customized adjuvant systemic treatment is to optimize the toxicity/benefit ratio, so that low-risk individuals are spared from unnecessary intervention, while avoiding undertreatment of high-risk patients, including those with stage I disease. Therefore, the application of reliable prognostic and predictive biomarkers would enable to identify appropriate patients for the most effective treatment.This is an overview of the data available on the most promising clinicopathological and molecular biomarkers that could affect adjuvant and neoadjuvant chemotherapy decisions for operable NSCLC in routine practice. Among the numerous candidate molecular biomarkers, only few gene-expression profiling signatures provide clinically relevant information warranting further validation. On the other hand, real-time quantitative polymerase-chain reaction strategy involving relatively small number of genes offers a practical alternative, with high cross-platform performance. Although data extrapolation from the metastatic setting should be cautious, the concept of personalized, pharmacogenomics-guided chemotherapy for early NSCLC seems feasible, and is currently being evaluated in randomized phase 2 and 3 trials. The mRNA and/or protein expression levels of excision repair cross-complementation group 1, ribonucleotide reductase M1 and breast cancer susceptibility gene 1 are among the most potential biomarkers for early disease, with stage-independent prognostic and predictive values, the clinical utility of which is being validated prospectively. Inter-assay discordance in determining the biomarker status and association with clinical outcomes is noteworthing.

Oncologic Outcomes After Surgical Resection of Subcentimeter Non-Small Cell Lung Cancer

The recent initiation of screening protocols and greater utilization of computed tomography has led to an increasing proportion of non-small cell lung cancer (NSCLC) patients presenting with subcentimeter stage IA tumors. The aim of this study was to compare the oncologic outcomes of lobectomy, segmentectomy, and wedge resection in patients with NSCLC tumors 1 cm or less in diameter. Data were extracted from medical records of patients undergoing surgical resection for stage IA NSCLC and a pathologically confirmed tumor diameter measuring 1 cm or less. Primary oncologic outcomes were disease recurrence and disease-free survival. Statistical comparisons were performed using Fisher's exact test and unpaired t test. Kaplan-Meier curves were compared using the log rank test. Significance was defined as a two-tailed p value less than 0.05. A total of 107 patients underwent complete (R0) surgical resection for stage IA NSCLC 1 cm or less in diameter (lobectomy, 32; segmentectomy, 40; wedge, 35). Age, sex distribution, tumor size, and histology were similar between groups. There was 1 perioperative mortality in the lobectomy group (3%). At a mean follow-up of 42.5 months, overall disease recurrence was equivalent, occurring in 3 lobectomy patients (9%), 4 segmentectomy patients (10%), and 3 wedge resection patients (9%; p=0.99). Estimated 5-year disease-free survival was comparable among cohorts (lobectomy, 87%; segmentectomy, 89%; wedge, 89%; p>0.402). Sublobar resections are associated with oncologic outcomes that are comparable to those of lobectomy for subcentimeter stage IA NSCLC, suggesting that they may be appropriate surgical interventions in this patient cohort. The validity of these observations needs to be assessed in a prospective setting.

Clinical utility of the new American Joint Committee on Cancer staging system for gastrointestinal stromal tumors

The objectives of the current study were to assess the reliability of the new revision of the American Joint Committee on Cancer (AJCC) staging system for gastrointestinal stromal tumors (GISTs) based on the National Comprehensive Cancer Network-Armed Forces Institute of Pathology risk classification and to analyze the factors that influence after resection for primary GISTs in 2 AJCC groups: patients with GISTs originating from the stomach and omentum (G-GISTs) and patients with other primary GISTs located mainly in the small bowel (nongastric GISTs [NG-GISTs]). The authors prospectively analyzed a group of 640 patients with primary, CD117-positive GISTs who underwent surgery with curative intention (R0/R1 resection), including 340 G-GISTs (55.5%) and 300 NG-GISTs (44.5%). Factors were explored that had an effect on disease-free survival time (DFS), which was calculated from the date of radical operation to the date of recurrence or last follow-up. The median follow-up was 39 months. Compared with NG-GISTs, G-GISTs were characterized by a significantly lower median size (5.3 cm and 8.5 cm, respectively; P < .0001) and lower mitotic activity (median, 3 in 50 high-power fields [HPF] vs 5 in 50 HPF; P < .0001), and they were diagnosed in older patients (median age, 62 years vs 57 years; P = .002). The most commonly detected mutations in G-GIST were those located in KIT exon 11 (60.5%) and platelet-derived growth factor receptor alpha (PDGFRA) exon 18 (19%) versus KIT exons 11 and 9 in NG-GISTs (72% and 17.4%, respectively). The prognosis of patients who had G-GISTs was significantly better compared that of patients who had NG-GISTs, with 5-year DFS rates of 69% (median, 83 months) versus 43% (median, 33 months), respectively (P < .00001). The most significant prognostic factors that correlated with shorter DFS in both G-GISTs and NG-GISTs were primary tumor size >5 cm and >10 cm (P < .0001) and mitotic index >5 in 50 HPF and >10 in 50 HPF (P < .0001). The 5-year DFS rates in G-GISTs according to AJCC stage categories were as follows: 96% for stage IA tumors, 92% for stage IB tumors, 51% for II tumors, 22% for stage IIIA tumors, and 22% for stage IIIB tumors (P < .0001). The 5-year DFS rates in NG-GISTs according to AJCC categories were as follows: 92% for stage I tumors, 66% for stage II tumors, 28% for IIIA tumors, and 16% for IIIB tumors (P < .0001). The high prognostic significance of the AJCC classification also was confirmed for overall survival data, including the impact of therapy with tyrosine kinase inhibitors. The reliability of AJCC risk classification after resection of primary GIST was confirmed for DFS and overall survival. Patients with primary G-GISTs had a better prognosis than patients with NG-GISTs. In both groups, primary tumor size and mitotic activity were the most important prognostic factors in terms of DFS.

Survival Following Lobectomy and Limited Resection for the Treatment of Stage I Non-small Cell Lung Cancer ≤ 1 cm in Size: A Review of SEER Data

Although lobectomy is the standard treatment for stage I non-small cell lung cancer (NSCLC), recent studies have suggested that limited resection may be a viable alternative for small-sized tumors. The objective of this study was to compare survival after lobectomy and limited resection among patients with stage IA tumors≤1 cm by using a large, US-based cancer registry.Using the Surveillance, Epidemiology, and End Results (SEER) registry, we identified 2,090 patients with stage I NSCLC≤1 cm in size who underwent lobectomy or limited resection (segmentectomy or wedge resection). We used propensity score analysis to adjust for potential differences in the baseline characteristics of patients in the two treatment groups. Overall and lung cancer-specific survival rates of patients undergoing lobectomy vs limited resection were compared in stratified and adjusted analyses, controlling for propensity scores.Overall, 688 (33%) patients underwent limited resection. For the entire cohort, we were not able to identify a difference in outcomes among patients treated with lobectomy vs limited resection, as demonstrated by an adjusted hazard ratio (HR) for overall survival (1.12; 95% CI, 0.93-1.35) and lung cancer-specific survival (HR, 1.24; 95% CI, 0.95-1.61). Similarly, when the cohort was divided into propensity score quintiles, we did not find a difference in survival rate between the two groups.Limited resection and lobectomy may lead to equivalent survival rates among patients with stage I NSCLC tumors≤1 cm in size. If confirmed in prospective studies, limited resection may be preferable for the treatment of small tumors because it may be associated with fewer complications and better postoperative lung function.

Comparative Performance of the 2009 International Federation of Gynecology and Obstetricsʼ Staging System for Uterine Corpus Cancer

To perform a population-based analysis comparing the performance of the 1988 and 2009 International Federation of Gynecology and Obstetrics (FIGO) staging systems. Women with endometrioid adenocarcinoma of the uterus treated between 1988 and 2006 and recorded in the Surveillance, Epidemiology, and End Results database were analyzed. Women were classified based on 1988 and 2009 FIGO staging systems. Major changes in the 2009 system include: 1) classification of patients with stage IA and IB tumors as stage IA; 2) elimination of stage IIA; and 3) stratification of stage IIIC into pelvic nodes only (IIIC1) or paraaortic nodal (IIIC2) involvement. Survival and use of adjuvant therapy were analyzed. A total of 81,902 women were identified. Based on the 1988 staging system, survival for stage IA was 90.7% (95% confidence interval [CI], 90-91%) compared with 88.9% (95% CI 88-89%) for IB tumors. In the 2009 system, survival was 89.6% (95% CI 89-90%) for stage IA and 77.6% (95% CI 76-79%) for stage IB. The survival for FIGO 1988 stage IIA was superior to stage IC, whereas in the 2009 system, survival for stage II was inferior to all stage I patients. The newly defined stage IIIC substages are prognostically different. Survival for stage IIIC1 was 57.0% (95% CI 54-60%) compared with 49.4% (95% CI 46-53%) for stage IIIC2. The 2009 FIGO staging system for uterine corpus cancer is highly prognostic. The reduction in stage I substages and the separation of stage III will further clarify important prognostic features. III.

Clinical outcomes of stereotactic body radiotherapy for stage I non-small cell lung cancer using different doses depending on tumor size

BackgroundThe treatment schedules for stereotactic body radiotherapy (SBRT) for lung cancer vary from institution to institution. Several reports have indicated that stage IB patients had worse outcomes than stage IA patients when the same dose was used. We evaluated the clinical outcomes of SBRT for stage I non-small cell lung cancer (NSCLC) treated with different doses depending on tumor diameter.MethodsBetween February 2004 and November 2008, 124 patients with stage I NSCLC underwent SBRT. Total doses of 44, 48, and 52 Gy were administered for tumors with a longest diameter of less than 1.5 cm, 1.5-3 cm, and larger than 3 cm, respectively. All doses were given in 4 fractions.ResultsFor all 124 patients, overall survival was 71%, cause-specific survival was 87%, progression-free survival was 60%, and local control was 80%, at 3 years. The 3-year overall survival was 79% for 85 stage IA patients treated with 48 Gy and 56% for 37 stage IB patients treated with 52 Gy (p = 0.05). At 3 years, cause-specific survival was 91% for the former group and 79% for the latter (p = 0.18), and progression-free survival was 62% versus 54% (p = 0.30). The 3-year local control rate was 81% versus 74% (p = 0.35). The cumulative incidence of grade 2 or 3 radiation pneumonitis was 11% in stage IA patients and 30% in stage IB patients (p = 0.02).ConclusionsThere was no difference in local control between stage IA and IB tumors despite the difference in tumor size. The benefit of increasing the SBRT dose for larger tumors should be investigated further.

Lung cancer growth dynamics

Mathematical modeling furnishes valuable and otherwise unattainable insights, some counterintuitive, into the natural history of lung cancer. We modeled lung cancer growth dynamics to show that: (1) early diagnosis of lethal lung cancer by means of radiographic or CT screening is an unattainable goal. (2) At a given dimension and constant tumor volume doubling time, the rate of diameter increase is an exponential function (base 1.26) of the number of tumor volume doublings, and the rate of increase in volume, a quadratic function of the radius. (3) This methodology delineates the magnitude of diameter increase in small nodules required to discern volume growth. (4) Under the assumption of a high degree of compliance with sequential screens in large-scale trials, mean tumor volume doubling time can be estimated from the prevalence:incidence ratio. For example, in the Mayo Clinic computerized tomography trial, stage IA tumor volume doubling time was 230 days.

Preoperative Chemotherapy Plus Surgery Versus Surgery Plus Adjuvant Chemotherapy Versus Surgery Alone in Early-Stage Non–Small-Cell Lung Cancer

To address whether preoperative chemotherapy plus surgery or surgery plus adjuvant chemotherapy prolongs disease-free survival compared with surgery alone among patients with resectable non-small-cell lung cancer. In this phase III trial, 624 patients with stage IA (tumor size > 2 cm), IB, II, or T3N1 were randomly assigned to surgery alone (212 patients), three cycles of preoperative paclitaxel-carboplatin followed by surgery (201 patients), or surgery followed by three cycles of adjuvant paclitaxel-carboplatin (211 patients). The primary end point was disease-free survival. In the preoperative arm, 97% of patients started the planned chemotherapy, and radiologic response rate was 53.3%. In the adjuvant arm, 66.2% started the planned chemotherapy. Ninety-four percent of patients underwent surgery; surgical procedures and postoperative mortality were similar across the three arms. Patients in the preoperative arm had a nonsignificant trend toward longer disease-free survival than those assigned to surgery alone (5-year disease-free survival 38.3% v 34.1%; hazard ratio [HR] for progression or death, 0.92; P = .176). Five-year disease-free survival rates were 36.6% in the adjuvant arm versus 34.1% in the surgery arm (HR 0.96; P = .74). In early-stage patients, no statistically significant differences in disease-free survival were found with the addition of preoperative or adjuvant chemotherapy to surgery. In this trial, in which the treatment decision was made before surgery, more patients were able to receive preoperative than adjuvant treatment.

Long-Term Oncologic Outcomes from Laparoscopic Gastrectomy for Gastric Cancer: A Single-Center Experience of 601 Consecutive Resections

Laparoscopic gastrectomy (LG) is becoming increasingly popular for management of early gastric cancer (EGC). Although short-term efficacy is proven, reports on long-term effectiveness are still infrequent. All patients with a diagnosis of gastric cancer undergoing LG from the beginning of our laparoscopic experience were included in the analysis. At our unit, LG is indicated for all cancers up to preoperative stage T2N1. Six-hundred and one laparoscopic resections were included in the analysis. There were 392 men and 209 women. Mean age was 64.2 +/- 10.9 years. Distal gastrectomy was performed in 305 patients, pylorus-preserving gastrectomy in 148, segmental gastrectomy in 42, proximal gastrectomy in 53, total gastrectomy in 27, and wedge resection in 26. Histological staging revealed that 478 patients had stage IA disease, 47 had stage IB, 44 had stage IIA, 19 had stage IIB, 8 had stage IIIA, 3 had stage IIIB, and 2 had stage IIIC. Morbidity and mortality rates were 17.6% and 0.3%, respectively. Median follow-up was 35.9 months (range 3 to 113 months). Cancer recurrence occurred in 15 patients and metachronous gastric remnant cancer was detected in 6 patients. The 5-year overall and disease-free survival rates were 94.2% and 89.9%, respectively, for stage IA tumors, 87.4% and 82.7% for stage IB, 80.8% and 70.7% for stage IIA, and 69.6% and 63.1% for stage IIB. In our experience, long-term oncological outcomes from LG for EGC are acceptable. Wherever expertise permits, LG should be considered as the primary treatment in patients with EGC.