Disease-free Interval In Patients Research Articles

Effect of Tumor Regression Grade on Survival and Disease-Free Interval in Patients Operated on for Locally Advanced Rectal Cancer.

Colorectal cancer is the fourth leading cause of cancer-related death in both men and women in our population. In this regard, rectal cancer accounts for more than half of colorectal cancer deaths, and its incidence is expected to increase in the coming years. There have been significant changes in neoadjuvant therapy regimens, with promising results, as demonstrated by the recent RAPIDO and PRODIGE23 studies. Around 40% of patients diagnosed with locally advanced rectal cancer show some degree of response to neoadjuvant treatment, with complete tumor regression observed in up to one in five patients. Retrospective observational study. A total of 181 patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by surgery were analyzed. Clinical and pathological data were collected from the patients, including assessment of tumor regression through histopathological studies after surgery. The Mandard tumor regression grading system was used to categorize tumor response into different grades. The results showed a significant association between the degree of tumor regression and several important clinical outcomes. Specifically, patients with higher tumor regression had significantly better disease-free survival than those with less regression (p = 0.004). In addition, tumor regression was also correlated with the incidence of local recurrence (p = 0.018) and distant metastasis (p = 0.032). These associations suggest that tumor responsiveness to neoadjuvant therapy may influence the long-term progression of the disease. Regarding tumor deposits and the presence of lymphadenopathy, these factors were also found to be significantly associated with clinical outcomes. Patients with tumor deposits had a higher incidence of local recurrence (p = 0.025) and distant metastases (p = 0.041), while the presence of lymphadenopathy increased the risk of local recurrence (p = 0.013). These findings highlight the importance of evaluating not only tumor regression but also other pathological markers to predict prognosis and guide clinical management. The degree of tumor regression was not an independent predictor of survival compared to other variables such as nodal stage and presence of tumor deposits. This indicates that while tumor regression is an important factor, other elements also play a crucial role in determining the prognosis of patients with locally advanced rectal cancer. This study provides additional evidence for the importance of tumor regression, tumor deposits, and lymphadenopathy as predictors of clinical outcomes in patients with rectal cancer treated with neoadjuvant chemoradiotherapy.

Expression of CD105 but not of E-cadherin is associated with malignancy recurrence and disease-free interval in laryngeal cancer in men.

In this study we analyzed CD105 (endoglin) and E-cadherin expression in laryngeal squamous cell carcinoma (LSCC) to evaluate their clinicopathologic significance. Expression of CD105 and E-cadherin was examined immunohistochemically using paraffin-embedded archival tissues of 72 (35 glottic and 37 supraglottic) previously untreated LSCC male patients. The mean value of the positively-stained microvessels for CD105 counted in four hot spots for each case was used as the final intratumoralmicrovessel density (MVD). A staining score of E-cadherin was calculated based on the percentage of cells stained (0-100%). MVD was significantly higher in patients with advanced TNM stage (P = 0.004) and younger than 65 (P = 0.008). Nodal metastases were more frequent in the cases with low E-cadherin expression (P = 0.000). Tumor recurrence was associated with advanced TNM stage (P = 0.035) and high MVD (P = 0.002). A high MVD was an independent predictor of malignancy recurrence (P = 0.021). The log-rank test showed a significant difference in the disease-free interval in patients stratified according to the MVD value (P = 0.016). Spearman's rank correlation test did not show a significant correlation between E-cadherin and CD105 expression. CD105-assessed MVD and expression of E-cadherin are promising prognostic factors for the outcome of patients with LSCC. Increased expression of CD105 could help predict patients with an increased risk of developing loco-regional recurrence after surgical treatment. Decreased E-cadherin expression is a potential predictor of lymph node metastases.

Disease-Free Interval and Tumor Stage Complementarily Predict the Biological Behavior of Recurrent Hepatocellular Carcinoma.

Currently used treatment algorithms were originally established based on the clinical outcomes of the initial treatment for primary hepatocellular carcinoma (HCC), and no strong evidence exists yet to suggest if these algorithms could also be applicable to patients with recurrent HCC after surgery. As such, this study sought to explore an optimal risk stratification method for cases of recurrent HCC for better clinical management. Among the 1616 patients who underwent curative resection for HCC, the clinical features and survival outcomes of 983 patients who developed recurrence were examined in detail. Multivariate analysis confirmed that both the disease-free interval (DFI) from the previous surgery and tumor stage at recurrence were significant prognostic factors. However, the prognostic impact of DFI seemed different according to the tumor stages at recurrence. While curative-intent treatment showed strong influence on survival [hazard ratio (HR), 0.61; P < 0.001] regardless of the DFI in patients with stage 0 or stage A disease at recurrence, early recurrence (< 6 months) was a poor prognostic marker in patients with stage B disease. The prognosis of patients with stage C disease was exclusively influenced by the tumor distribution or choice of treatment than by the DFI. The DFI complementarily predicts the oncological behavior of recurrent HCC, with its predictive value differing depending on the tumor stage at recurrence. These factors should be considered for selection of the optimal treatment in patients with recurrent HCC after curative-intent surgery.

Ekspresija survivina u oralnom skvamocelularnom karcinomu

Introduction: Survivin functions as an apoptosis inhibitor and a regulator of cell division. This study aimed to determine the correlation between survivin expression and clinicopathologic parameters of oral squamous cell carcinoma (OSCC) and determine its potential role in the progression/prognosis of this type of tumor. Materials and methods: Immunohistochemical analysis of survivin expression was performed on 45 surgically obtained paraffin-embedded tissue samples of OSCCs. Data on patients' gender, age, tumor grade, site and stage, disease recurrence, metastasis occurrence , and disease-free interval (DFI) were correlated to survivin expression. Results: Survivin immunoreactivity was observed in 77.8% of samples. No significant correlation between survivin expression and age (p = 0.087), gender (p = 0.334), tumor site (p = 0.175), presence of lymph node metastases (p = 0.201), or disease recurrence (p = 0.451) was found. Survivin expression was observed in well and moderately differentiated tumors and in all clinical stages (p = 0.139). Patients with low survivin expression had better survival rates than the group with medium and high survivin expression, i.e., there was a tendency of a shorter DFI in patients with higher expression of survivin (p = 0.065). Conclusion: There is a tendency for a shorter disease-free period in patients with higher survivin expression. These data suggest that survivin expression in OSCC may act as an additional prognostic parameter that indicates an increased proliferative tumor potential. To further validate survivin as a prognostic marker in OSCC, a study with a larger sample size along with clinical follow-up data is needed.

MicroRNA-139-5p negatively regulates NME1 expression in hepatocellular carcinoma cells

High expression of NME1 is associated with hepatocellular carcinoma (HCC) progression and poor prognosis. However, there are few reports on the association between NME1 and microRNAs (miRNAs) in HCC progression. To explore miRNAs that regulate NME1 expression in HCC. Data from the Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), TargetScan, starBase, and mirDIP were used to analyze the expression pattern of NME1 in HCC tissues, the relationship between NME1 level and the progression of HCC or patient prognosis, miRNAs targeting NME1, and the biological processes that may be regulated by NME1. The regulation of miRNAs to NME1 was assessed using the dual-luciferase reporter assay, quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. The cell cycle and cell proliferation were detected using propidium iodide (PI) staining and EdU assay, respectively. Highly expressed NME1 in HCC was associated with HCC progression and prognosis. The miR-139-5p and miR-335-5p were weakly expressed in HCC samples and negatively correlated with NME1. The downregulation of miR-139-5p in HCC patients resulted in worse overall survival (OS) and disease-free interval (DFI); however, the level of miR-335-5p was not significantly correlated with OS and DFI in patients with HCC. In vitro experiments verified that the level of miR-139-5p was lower and NME1 expression was higher in HCC cell lines compared to L-02. Moreover, miR-139-5p negatively regulates the expression of NME1 in HCC cell lines. The NME1 may regulate cell cycle, DNA replication, oxidative phosphorylation, and the pentose phosphate pathway. The miR-139-5p inhibited cell proliferation by negatively regulating NME1 expression. The upregulation of NME1 in HCC indicates a poor prognosis. The NME1 is negatively regulated by miR-139-5p to inhibit cell proliferation.

Cytoreductive surgery with hyperthermic intrathoracic chemotherapy for malignant pleural mesothelioma: a systematic review

IntroductionCytoreductive surgery has been used a part of multimodality treatment in patients with malignant pleural mesothelioma (MPM). The residual microscopic disease that remains will lead to disease progression in the...

Solid Tumor Opioid Receptor Expression and Oncologic Outcomes: Analysis of the Cancer Genome Atlas and Genotype Tissue Expression Project.

BackgroundOpioid receptors are expressed not only by neural cells in the central nervous system, but also by many solid tumor cancer cells. Whether perioperative opioids given for analgesia after tumor resection surgery might inadvertently activate tumor cells, promoting recurrence or metastasis, remains controversial. We analysed large public gene repositories of solid tumors to investigate differences in opioid receptor expression between normal and tumor tissues and their association with long–term oncologic outcomes.MethodsWe investigated the normalized gene expression of µ, κ, δ opioid receptors (MOR, KOR, DOR), Opioid Growth Factor (OGFR), and Toll-Like 4 (TLR4) receptors in normal and tumor samples from twelve solid tumor types. We carried out mixed multivariable logistic and Cox regression analysis on whether there was an association between these receptors’ gene expression and the tissue where found, i.e., tumor or normal tissue. We also evaluated the association between tumor opioid receptor gene expression and patient disease–free interval (DFI) and overall survival (OS).ResultsWe retrieved 8,780 tissue samples, 5,852 from tumor and 2,928 from normal tissue, of which 2,252 were from the Genotype Tissue Expression Project (GTEx) and 672 from the Cancer Genome Atlas (TCGA) repository. The Odds Ratio (OR) [95%CI] for gene expression of the specific opioid receptors in the examined tumors varied: MOR: 0.74 [0.63–0.87], KOR: 1.27 [1.17–1.37], DOR: 1.66 [1.48–1.87], TLR4: 0.29 [0.26–0.32], OGFR: 2.39 [2.05–2.78]. After controlling all confounding variables, including age and cancer stage, there was no association between tumor opioid receptor expression and long–term oncologic outcomes.ConclusionOpioid receptor gene expression varies between different solid tumor types. There was no association between tumor opioid receptor expression and recurrence. Understanding the significance of opioid receptor expression on tumor cells remains elusive.

Recurrence and disease-specific survival after 10-year disease-free interval in patients with primary retroperitoneal liposarcoma: Implications for long-term surveillance.

11546 Background: Surveillance imaging of patients with retroperitoneal liposarcoma (RP-LPS) following surgical resection is based on a projected risk of locoregional and distant recurrence. The duration of surveillance is not well defined as the long-term natural history of RP-LPS after treatment is poorly understood. We evaluate a cohort of RP-LPS patients—without evidence of disease 10 years following initial resection—to assess the long-term risk of recurrence and disease-specific survival (DSS). Methods: The prospectively maintained UCLA Sarcoma Database was used to identify RP-LPS patients who demonstrated 10-year progression-free survival (10yr-PFS) after initial diagnosis and treatment. Patients in the 10yr-PFS cohort were subsequently evaluated for recurrence and DSS. Time intervals start at date of initial surgical resection. Cox proportional hazards models were used to determine factors associated with recurrence and DSS. Results: From 1972-2010, 76 patients with RP-LPS had at least 10 years of follow-up. Of these, 37 (49%) demonstrated 10yr-PFS. Median follow-up was 15 years (range 10-35 years). Among the 10yr-PFS patients, 43% (16/37) developed a recurrence &gt;10 years after the initial surgery, and 19% (7/37) died of disease. Neither long-term recurrence nor DSS were significantly associated with age, sex, tumor size, LPS subtype, surgical margin, or peri-operative treatment with radiation or chemotherapy (Table). Conclusions: Patients with primary RP-LPS treated with surgical resection +/- multimodality therapy have a long-term risk of recurrence and disease-specific death that is unacknowledged by current surveillance imaging guidelines. Among the patients with a 10yr-PFS, 43% developed a recurrence and 19% died of disease. These findings suggest a need for lifelong surveillance imaging in patients with RP-LPS.[Table: see text]

Clinical effect of the pathological axillary assessment method in breast cancer without clinical nodal metastasis

This study aimed to assess the clinical effect of the pathological axillary assessment method in breast cancer without clinical lymph node metastasis. Data of patients with clinically node-negative breast cancer were retrospectively reviewed. The study period was divided into early (January 2000-July 2007) and late (August 2007-December 2014) periods based on the pathological assessment method used (single-sectional and detailed multi-sectional lymph node processing). In the late period, lymph nodes were evaluated at six levels including immunohistochemistry on each 1.5-2mm interval section. The axillary diagnostic accuracy and role of chemotherapy were assessed. In 1698 patients, 27 isolated tumor cells (ITCs), 39 micrometastases, and 205 macrometastases were noted. The sensitivity for pathological N0 diagnosis was dependent on clinical T stage, Tis (97.8%), T1 (83.0%), T2 (74.2%), T3 (54.5%), and T4 (63.6%). ITCs and micrometastases were detected only in the late period, and 84.7% and 91.6% of cases in the early and late period, respectively, did not have macrometastases. The 5-year disease-free interval (DFI) rates were 95.2% in node-negative cases, 98.4% in ITCs/micrometastases, and 91.4% in macrometastases (P < 0.001). In multivariate analysis, the predictor for DFI was estrogen receptor negativity (P = 0.013). Chemotherapy did not improve DFI in patients with node-positive breast cancer. The detailed multi-sectional pathological assessment of axillary lymph nodes detected ITCs and micrometastases. Implementation of chemotherapy should not be based on the minimal nodal metastasis and this type of serially nodal sectioned processing had little clinical significance.

Prognostic significance of histopathological factors in survival and recurrence of atypical carcinoid tumours.

Atypical carcinoids are neuroendocrine neoplasms of intermediate degree and low frequency. The aim of this study is to analyse their clinical characteristics and the importance of different histopathological factors in their prognosis. Multicentre cooperative group EMETNE prospectively reviewed 153 patients operated on between 1998 and 2016 with diagnosis of atypical carcinoids. Clinical variables and histopathological features were assessed. Mean age was 54.36 years, similar for both genders. Concerning pathological study, mean tumour size was 31.7 mm. Rosettes were presented in 17% of the cases and tumoural necrosis in 23.3%. The cell proliferation factor Ki-67 index was 10.7%. The 2- and 5-year overall survival rates were 95.8% and 88.9%, respectively. In the univariate study, statistically significant differences in survival were found for each of the categories of T, N and M factors. Mitotic index and quantification of expression of Ki-67 showed influence in overall survival, although without statistical significance. In the multivariate analysis, factors N, M and mitotic index behaved as independent prognostic factors related to survival. Median disease-free interval in the series was 163.35 months. In cases with loco-regional recurrence, 53% had positive hiliar or mediastinal nodal involvement at the time of the surgery. In the univariate analysis, we observed statistically significant differences in disease-free interval in patients with nodal involvement (P = 0.024) and non-anatomical resections (P = 0.04). Histological characteristics showed no statistically significant differences in disease-free interval. Lymph node involvement, the development of distant metastasis and mitotic index, more than Ki-67 determination, were shown as independent prognostic factors related to survival of these patients.

Strategies to prevent brain metastasis.

The current article reviews the state of art of prevention strategies for brain metastases from solid tumors and touches both old pivotal studies and new directions of personalized molecular approaches. Prophylactic cranial irradiation (PCI) has a definite role in the prevention of relapse into the brain for patients with small cell lung cancer (SCLC) responding to chemotherapy and radiotherapy as it prolongs overall survival (OS). However, the risk of late cognitive deficit following whole brain radiotherapy (WBRT) in this patient population is still not well known. Conversely, PCI significantly reduces the incidence of brain metastases and prolongs the disease-free interval in patients with non-SCLC (NSCLC), but does not improve OS thus far. Pharmacologic prevention is a new concept driven by the efficacy of targeted agents on macrometastases from specific molecular subgroups. The future challenges for prevention of brain metastases are represented by the identification of subgroups of patients at higher risk of relapse into the brain coupled with either new WBRT strategies to better preserve cognition or effective molecular agents to target micrometastases.

The Disease-Free Interval Between Resection of Primary Colorectal Malignancy and the Detection of Hepatic Metastases Predicts Disease Recurrence But Not Overall Survival

IntroductionThe disease-free interval (DFI) between resection of primary colorectal cancer (CRC) and diagnosis of liver metastases is considered an important prognostic indicator; however, recent analyses in metastatic CRC found limited evidence to support this notion.ObjectiveThe current study aims to determine the prognostic value of the DFI in patients with resectable colorectal liver metastases (CRLM).MethodsPatients undergoing first surgical treatment of CRLM at three academic centers in The Netherlands were eligible for inclusion. The DFI was defined as the time between resection of CRC and detection of CRLM. Baseline characteristics and Kaplan–Meier survival estimates were stratified by DFI. Cox regression analyses were performed for overall (OS) and disease-free survival (DFS), with the DFI entered as a continuous measure using a restricted cubic spline function with three knots.ResultsIn total, 1374 patients were included. Patients with a shorter DFI more often had lymph node involvement of the primary, more frequently received neoadjuvant chemotherapy for CRLM, and had higher number of CRLM at diagnosis. The DFI significantly contributed to DFS prediction (p =0.002), but not for predicting OS (p =0.169). Point estimates of the hazard ratio (95% confidence interval) for a DFI of 0 versus 12 months and 0 versus 24 months were 1.284 (1.114–1.480) and 1.444 (1.180–1.766), respectively, for DFS, and 1.111 (0.928–1.330) and 1.202 (0.933–1.550), respectively, for OS.ConclusionThe DFI is of prognostic value for predicting disease recurrence following surgical treatment of CRLM, but not for predicting OS outcomes.

Depth of Response in Waldenstrom Macroglobulinemia

IntroductionRecent advances in the understanding of the WM pathobiology led to the expansion of our therapeutic options in this disease. A number of targeted drugs are either available or under investigation and are poised to change the chemo-immunotherapy paradigm in the treatment of WM. Now more than ever, an individualized treatment approach for patients with WM is possible, where patient characteristics and preferences can be matched by different treatment goals and side effect profiles. While deep responses have been associated with longer disease-free survival in other hematologic malignancies, data on patients with WM are sparse. We report the impact of depth of response in disease-free and overall survival (OS) in WM.MethodsWM patients consecutively seen at Mayo Clinic between 01/1998 and 12/2016 were reviewed for response to therapy and disease burden. The best response achieved after the treatment of interest (TOI) was classified using the IWWM-7 Response Criteria. The included TOI were: BR, DRC, BDR and high-dose chemotherapy followed by ASCT. All time-to-event analyses were performed from the TOI initiation date using the Kaplan-Meier method and the log-rank test. A landmark analysis from the date-of-best response was also performed for OS to prevent immortal-time bias. Univariate and multivariate analyses of progression-free survival (PFS) and time-to-next therapy (TTNT) were performed using the Cox regression method.ResultsA total of 181 patients had disease response assessed after the TOI. Baseline characteristics at time of diagnosis are summarized in table 1. The median follow up from TOI was 3.8 years (95% CI: 3-4), the majority of patients received TOI as salvage therapy [n=112 (63%); median 2nd line (rage 1-11)]. Best response rates with the corresponding 5-year PFS and TTNT are summarized in table 2.The median OS from TOI was longer in patients who achieved at least a PR [median 7.2 years (95% CI: 5-NR) vs 3.7 years (95% CI: 1.6-NR), p=0.01]. A trend towards a longer OS was also seen with deeper responses (PR or better) achieved with frontline therapy [median 5.8 years (95% CI: 5.8-NR) vs 3.4 years (95% CI: 1.6-NR), p=0.24]. Figure 1 shows the correlation between deeper responses with PFS and TTNT.Among patients achieving a PR or VGPR, those with a normal FLC ratio post TOI demonstrated a longer PFS and TTNT [PFS: median NR (95% CI: 3.4-NR) vs 4.9 years (95% CI: 2.8-8.7), p=0.01; TTNT: median NR (95% CI: 3.5-NR) vs 5.2 years (95% CI: 4.2-9.4), p=0.04], figure 2. In a multivariate analysis including normal FLC ratio, normal IgM level and minimal BM involvement (<5%) post TOI, normal FLC ratio remained an independent prognostic factor for longer PFS and TTNT. Similar trends were seen when considering treatment naïve and relapsed/refractory patients independently (data not shown).DiscussionOur results not only suggest an association between depth of response with PFS and TTNT, but also with OS in patients with WM. A normal FLC ratio (not part of the IWWM-7 response criteria) seems to predict a longer disease-free interval in patients achieving a PR or VGPR. [Display omitted] DisclosuresGertz:Ionis: Honoraria; Apellis: Consultancy; annexon: Consultancy; Prothena: Honoraria; janssen: Consultancy; Physicians Education Resource: Consultancy; Alnylam: Honoraria; Teva: Consultancy; spectrum: Consultancy, Honoraria; Medscape: Consultancy; celgene: Consultancy; Research to Practice: Consultancy; Amgen: Consultancy; Abbvie: Consultancy. Kapoor:Takeda: Research Funding; Celgene: Research Funding. Ailawadhi:Amgen: Consultancy; Janssen: Consultancy; Takeda: Consultancy; Pharmacyclics: Research Funding; Celgene: Consultancy. Reeder:Affimed: Research Funding. Witzig:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Dispenzieri:Celgene, Takeda, Prothena, Jannsen, Pfizer, Alnylam, GSK: Research Funding. Lacy:Celgene: Research Funding. Kumar:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Ansell:Seattle Genetics: Research Funding; Celldex: Research Funding; Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Pfizer: Research Funding; Takeda: Research Funding; Merck & Co: Research Funding; Affimed: Research Funding; Regeneron: Research Funding.

Abstract P2-12-09: Long-term follow-up of nipple-sparing mastectomy for early-stage breast cancer without radiotherapy: A single-center study at a Japanese institution

Abstract Introduction: Achievement of a good cosmetic outcome is one of the most important goals of surgical treatment of breast cancer. However, most patients must undergo a mastectomy if the outcome of breast-conserving surgery is discordant. All potential techniques that maintain oncological safety should be considered to maximize the cosmetic outcome for patients who require a mastectomy. We began performing nipple-sparing mastectomy (NSM) in 1978. Recent reports have suggested that NSM is oncologically as safe as mastectomy and affords a better cosmetic outcome. Conversely, the surgical complications and recurrence associated with NSM remain controversial. Objective: In the present study, we review the safety of the NSM surgical technique, discuss nipple–areola recurrence and skin flap recurrence after NSM, and compare recurrence and prognosis between NSM and mastectomy based on our long-term follow-up data. Patients and Methods: We retrospectively analyzed 723 patients with early-stage breast cancer who underwent NSM from 1985 to 2007. The patients' median age, tumor size, and tumor–areola distance were 50 y, 2.1 cm, and 1.5 cm, respectively. We used a thick skin flap method to avoid surgical complications including nipple and skin flap necrosis. We analyzed nipple–areola recurrence and skin flap recurrence after NSM. We also analyzed 100 patients who underwent mastectomy for early-stage breast cancer during the same period as those who underwent NSM. We compared the local recurrence rate (LRR), disease-free survival (DFS) rate, and overall survival (OS) rate among all 723 patients who underwent NSM and 100 patients who underwent mastectomy. No patients in either group received radiotherapy. Results: Among all patients who underwent NSM, stage 0, 1, 2A, and 2B disease was present in 21, 320, 253, and 129 patients, respectively. Notably, no nipple necrosis occurred during the average 114-month follow-up period. Local recurrence developed in 49 patients (6.7%), including recurrence at the nipple–areola complex in 24 (3.3%) and recurrence at the skin flap in 25 (3.4%). The average disease-free interval in patients with nipple–areola recurrence was 50 months, and that in patients with skin flap recurrence was 68 months. The clinical features of nipple–areola recurrence were a low rate of ER positivity (27%), high rate of Her2/neu positivity (60%), Paget type recurrence rate of 52%, and small tumor–areola distance (0.5 cm). The clinical features of skin flap recurrence were a relatively high rate of ER positivity (55%), solitary type recurrence rate of 88%, and diffuse type recurrence rate of 12%. The prognosis of diffuse type skin flap recurrence was significantly worse than that of solitary type recurrence (p = 0.01). There were no significant differences between the NSM and mastectomy groups in the LLR (6.7% vs. 4.0%, respectively), 10-y DFS rate (88% vs. 90%, respectively), or 10-y OS rate (92% vs. 91%, respectively). Conclusion: Our long-term follow-up data show that NSM should be considered as an alternative option for mastectomy when the outcome of breast-conserving surgery is discordant in patients with early-stage breast cancer. Citation Format: Sakurai T, Suzuma T, Yoshimura G, Jinta E, Umemura T, Sakurai T. Long-term follow-up of nipple-sparing mastectomy for early-stage breast cancer without radiotherapy: A single-center study at a Japanese institution. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-12-09.

Prognostic Indicators for Salvage Surgery of Recurrent Sinonasal Malignancy.

Identify prognostic factors after salvage surgery for recurrent sinonasal malignancy (SNM). Case series with chart review. University of Pittsburgh Medical Center. Forty-two patients who underwent curative surgery for locally recurrent SNM ± adjuvant therapy from June 5, 2000, to December 19, 2012. Patients without follow-up were excluded. Chart review with established prognostic indicators for primary malignancies. Statistical analysis included Kaplan-Meier log-rank test, Fisher's exact test, Student's t test, and Cox regression. Forty-two patients met inclusion criteria: 38.5% developed a second recurrence, and 21.4% had metastases following treatment. The average disease-free interval (DFI) was 26.9 months (range, 2-90 months). DFI was significantly affected by ethmoid versus nonethmoid site (P = .049), histology (P = .012), carotid artery involvement (P = .008), perineural extension (P = .006), and clival invasion (P = .015). The overall survival rates at 6 months, 12 months, and 5 years following surgery were 83.3%, 69%, and 47.6%, respectively. Survival was affected by histology (P = .014), stratified grade (P = .042), tumor extension into the orbit (P = .019), carotid artery (P = .001), perineural space (P = .028), and clivus (P = .022). Complications occurred in 28.6% of patients and were associated with histology (P = .04). Length of hospital stay related to treatment was affected by histology (P = .009), grade (P = .013), and postoperative complication (P < .001). The median percentage of time hospitalized was 8%, and 43% of patients who died within 12 months spent >10% of their remaining days in the hospital. High-risk histologic subtype (melanoma, sinonasal undifferentiated carcinoma, adenocarcinoma, neuroendocrine cancer, sarcoma, and squamous cell carcinoma), grade, and orbital and skull base involvement negatively affect survival and/or DFI for patients with local recurrence of SNM. Improved stratification of patients can be used to guide decision making for patients with recurrent SNM and to avoid inappropriate surgery.

The significance of paracardiac lymph-node enlargement in patients with newly diagnosed stage IIIC ovarian cancer

ObjectiveExtra-abdominal metastases in epithelial ovarian cancer (EOC) are relatively rare. Interpreting computed tomography (CT) scans, during initial work-up, little attention is focused on enlargement of paracardiac lymph nodes (PCLN) and their significance is not clear. We aimed to examine whether the presence of PCLN during initial diagnosis of EOC influences prognosis. MethodsA retrospective study comparing patients with stage 3 EOC who were diagnosed with PCLN on CT scan during initial evaluation to stage 3C patients without PCLN. Scans were reviewed by a single radiologist for peritoneal involvement, distal metastases and presence of PCLN. Disease status at diagnosis, results of surgery, chemotherapy and response, disease-free interval (DFI) and overall survival (OS) were recorded. ResultsThirty one patients with stage 3C EOC with PCLN on initial CT scan were included and compared with 41 controls. There was no significant difference between groups in abdominal optimal cytoreduction rate. Lower rates of complete response (CR) to initial treatment were detected in the study group (45.2% vs. 78.0%, p=.004). In survival analysis, the DFI for patients with PCLN was shorter (median 9.0 vs. 24.0months, p=.0097) and overall survival was shorter (median 31.7 vs. 61.3months, p=.001). Multivariate analysis showed that PCLN was significantly associated with a lower rate of CR, a shorter DFI and a shorter OS. ConclusionThe presence of enlarged PCLN at presentation appears to be associated with poor prognosis in stage 3C EOC. Further attention should be given to detection and follow-up of such findings when considering treatment.

Adjuvant bevacizumab in patients with melanoma at high risk of recurrence (AVAST-M): preplanned interim results from a multicentre, open-label, randomised controlled phase 3 study

Bevacizumab, a monoclonal antibody that targets VEGF, has shown restricted activity in patients with advanced melanoma. We aimed to assess the role of bevacizumab as adjuvant treatment for patients with resected melanoma at high risk of recurrence. We report results from the preplanned interim analysis. We did a multicentre, open-label, randomised controlled phase 3 trial at 48 centres in the UK between July 18, 2007, and March 29, 2012. Patients aged 16 years or older with American Joint Committee on Cancer stage (AJCC) stage IIB, IIC, and III cutaneous melanoma were randomly allocated (1:1), via a central, computer-based minimisation procedure, to receive intravenous bevacizumab 7.5 mg/kg, every 3 weeks for 1 year, or to observation. Randomisation was stratified by Breslow thickness of the primary tumour, N stage according to AJCC staging criteria, ulceration of the primary tumour, and patient sex. The primary endpoint was overall survival; secondary endpoints included disease-free interval, distant-metastases interval and quality of life. Analysis was by intention-to-treat. This trial is registered as an International Standardised Randomised Controlled Trial, number ISRCTN81261306. 1343 patients were randomised to either the bevacizumab group (n=671) or the observation group (n=672). Median follow-up was 25 months (IQR 16-37) in the bevacizumab group and 25 months (17-37) in the observation group. At the time of interim analysis, 286 (21%) of 1343 enrolled patients had died: 140 (21%) of 671 patients in the bevacizumab group, and 146 (22%) of 672 patients in the observation group. 134 (96%) of patients in the bevacizumab group died because of melanoma versus 139 (95%) in the observation group. We noted no significant difference in overall survival between treatment groups (hazard ratio [HR] 0.97, 95% CI 0.78-1.22; p=0.76); this finding persisted after adjustment for stratification variables (HR 1.03; 95% CI 0.81-1.29; p=0.83). Median duration of treatment with bevacizumab was 51 weeks (IQR 21-52) and dose intensity was 86% (41-96), showing good tolerability. 180 grade 3 or 4 adverse events were recorded in 101 (15%) of 671 patients in the bevacizumab group, and 36 (5%) of 672 patients in the observation group. Bevacizumab resulted in a higher incidence of grade 3 hypertension than did observation (41 [6%] vs one [<1%]). There was an improvement in disease-free interval for patients in the bevacizumab group compared with those in the observation group (HR 0.83, 95% CI 0.70-0.98, p=0.03), but no significant difference between groups for distant-metastasis-free interval (HR 0.88, 95% CI 0.73-1.06, p=0.18). No significant differences were noted between treatment groups in the standardised area under the curve for any of the quality-of-life scales over 36 months. Three adverse drug reactions were regarded as both serious and unexpected: one patient had optic neuritis after the first bevacizumab infusion, a second patient had persistent erectile dysfunction, and a third patient died of a haemopericardium after receiving two bevacizumab infusions and was later identified to have had significant predisposing cardiovascular risk factors. Bevacizumab has promising tolerability. Longer follow-up is needed to identify an effect on the primary endpoint of overall survival at 5 years.

Learning Curve for D2 Lymphadenectomy in Gastric Cancer

Background. D2 lymphadenectomy is a demanding technique which is associated with high morbidity in the West. We report our experience with D2 lymphadenectomy after a training period in Japan. Methods. Prospective, descriptive study in 133 consecutive patients undergoing radical gastrectomy for gastric adenocarcinoma from 2005 to 2011. We analysed the number of lymph nodes removed, observed morbidity/mortality compared with the predictions of POSSUM and O-POSSUM, survival, and disease-free interval for patients with D1 and D2 lymphadenectomy. Results. The morbidity rate in patients with D1 lymphadenectomy was 59.4%. For D2 it was 47.7%. The mortality rate in patients with D1 was 6.7%. In the D2 group it was 6.8%. Median survival was 42.9 months in D1 and 55 months in D2. The disease-free interval was 49 months for D1 and 58 months for D2. Conclusion. The learning curve for D2 lymphadenectomy presents acceptable rates of morbidity and mortality, providing that the technique is learnt at a center with extensive experience.

883 - Experience of Organ Preservation in Urinary Bladder

ABSTRACT Aims A retrospective analysis to evaluate the toxicity profile, protocol completion rate, tumor response rate, and disease free interval in patients undergoing chemoradiotherapy with muscle-invasive bladder cancer. Materials and methods Following transurethral resection of the tumor in patients with Stage T2-T4a bladder cancer, induction chemotherapy with paclitaxel and cisplatin / gemcitabine and cisplatin was administered for two–three cycles. Thereafter radiotherapy with low dose chemotherapy was administered with weekly review. Adjuvant chemotherapy based on the neoadjuvant protocol was given to all patients. Results Between May 2005 to April 2008 total of 109 patients database were available for review. Paclitaxel and cisplatin chemotherapy resulted in mildly grater grade 3-4 acute toxicity, mainly gastrointestinal (25%) as compared with gemcitabine and cisplatin 17%. Four cycles of adjuvant chemotherapy were completed per protocol or with minor deviations in 45% of the patients in both the arms together. Late bladder radiation toxicity was evaluated in 47 patients with >/ = 2 years of follow-up. Of these 47 patients, 3 experienced self-limited, late grade 3 bladder toxicity. The post induction complete response rate was 81% and 76% in the Paclitaxel and cisplatin group and gemcitabine and cisplatin group respectively. At a median follow-up of 39.4 months, the disease free survival was 69% and 71%, respectively. Conclusions These favorable tumor response rates with possible increased bladder preservation rates suggest that this treatment regimen deserves further study. Disclosure All authors have declared no conflicts of interest.

Lymph node micrometastases detected by carcinoembryonic antigen mRNA affect long-term survival and disease-free interval in early-stage lung cancer patients

The majority of stage I lung cancer patients undergo a complete resection of their tumor; however, they still harbor a considerable risk of mortality due to recurrences. A correlation between the presence of lymph node micrometastases and poor prognosis has been observed. The aim of this study was to correlate the lymph node molecular staging with the 5-year survival and disease-free interval following pulmonary lobectomy for non-small cell lung cancer (NSCLC). A quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for carcinoembryonic antigen (CEA) mRNA was performed on primary lung tumors and regional lymph nodes from 55 surgically resected NSCLC patients classified as clinical stage I. CEA mRNA was found to be present in all the primary tumors. RT-PCR revealed the presence of cancer cells in the lymph nodes of 20 patients (36.3%) and routine staining detected lymph node metastases in 11 patients. Significant differences in survival and disease-free intervals were observed in patients with lymph node micrometastases versus patients with negative lymph nodes (P=0.0026 and P=0.0044, respectively). Multivariate analyses confirmed that micrometastases were an independent predictor for worse prognosis (P=0.0098) and a short disease-free interval (P=0.0137). This study demonstrated strong correlations between the molecular detection of lymph node micrometastases and 5-year survival rates and disease-free interval in patients who underwent pulmonary lobectomy for early-stage lung cancer.