Microscopic Residual Disease Research Articles

Premalignant SOX2 overexpression in the fallopian tubes of ovarian cancer patients: Discovery and validation studies

Current screening methods for ovarian cancer can only detect advanced disease. Earlier detection has proved difficult because the molecular precursors involved in the natural history of the disease are unknown. To identify early driver mutations in ovarian cancer cells, we used dense whole genome sequencing of micrometastases and microscopic residual disease collected at three time points over three years from a single patient during treatment for high-grade serous ovarian cancer (HGSOC). The functional and clinical significance of the identified mutations was examined using a combination of population-based whole genome sequencing, targeted deep sequencing, multi-center analysis of protein expression, loss of function experiments in an in-vivo reporter assay and mammalian models, and gain of function experiments in primary cultured fallopian tube epithelial (FTE) cells. We identified frequent mutations involving a 40kb distal repressor region for the key stem cell differentiation gene SOX2. In the apparently normal FTE, the region was also mutated. This was associated with a profound increase in SOX2 expression (p<2−16), which was not found in patients without cancer (n=108). Importantly, we show that SOX2 overexpression in FTE is nearly ubiquitous in patients with HGSOCs (n=100), and common in BRCA1-BRCA2 mutation carriers (n=71) who underwent prophylactic salpingo-oophorectomy. We propose that the finding of SOX2 overexpression in FTE could be exploited to develop biomarkers for detecting disease at a premalignant stage, which would reduce mortality from this devastating disease.

Prognosis of patients with esophageal squamous cell carcinoma who achieve major histopathological response after neoadjuvant chemoradiotherapy

BackgroundThe purpose of this study was to investigate the prognosis and its predictors in patients with esophageal squamous cell carcinoma (ESCC) who achieve major histopathological response (MaHR) after neoadjuvant chemoradiotherapy (nCRT). MethodsWe examined a total of 187 ESCC patients who achieved MaHR following nCRT and survived the perioperative period. MaHR was defined as either absence or <10% vital residual tumor cells (VRTC) in the resected esophagus without nodal involvement. Univariate and multivariate analyses were used to identify factors significantly associated with overall survival (OS). ResultsAt the time of analysis, 113 patients (60.4%) were dead (5-year OS = 48%; median survival time = 54.8 months). The amount of VRTC (1–10% versus 0% VRTC; hazard ratio [HR] = 1.9, P < 0.001) and the thoroughness of histopathological examination (standard [≤ 4 tumor blocks] versus thorough [> 4 tumor blocks], HR = 1.57; P = 0.013) were independent predictors of OS in multivariate analysis. A stepwise increase in OS was observed in the following groups: patients with 1–10% VRTC identified by the standard protocol, patients with 1–10% VRTC identified by the thorough protocol, patients with 0% VRTC identified by the standard protocol, and patients with 0% VRTC identified by the thorough protocol (5-year OS rates = 20%, 40%, 50%, and 62%, respectively, P < 0.001). ConclusionsIn ESCC patients who achieve MaHR after nCRT, the presence of microscopical residual disease and the thoroughness of histopathological examination are associated with survival.

Primary cardiac angiosarcoma: a prolonged response to surgical resection followed by concurrent chemoradiotherapy with docetaxel.

IntroductionPrimary cardiac cancer is a very rare disease, among which primary cardiac angiosarcoma is one of the most frequent type and is characterized by extremely poor prognosis without established optimal treatment.Case descriptionHere we report a case of primary cardiac angiosarcoma with hemorrhagic pericardial effusion who achieved a durable response with tumor excision followed by concurrent chemoradiotherapy with docetaxel. A sixty year old man was presented with dyspnea and was diagnosed with primary cardiac angiosarcoma with hemorrhagic pericardial effusion. After surgical excision of primary tumor with microscopic residual disease followed by concurrent chemoradiotherapy with docetaxel, the patient showed durable response of progression free survival of 12 months.Discussion and evaluationThis case shows benefit of concurrent chemoradiotherapy with taxane. Further investigation of aggressive multimodal treatment strategy is warranted for primary cardiac angiosarcoma with pauci-metastasis even when achievement of complete resection seems unlikely.

Radiation Therapy after Radical Prostatectomy: Implications for Clinicians.

Depending on the pathological findings, up to 60% of prostate cancer patients who undergo radical prostatectomy (RP) will develop biochemical relapse and require further local treatment. Radiotherapy (RT) immediately after RP may potentially eradicate any residual localized microscopic disease in the prostate bed, and it is associated with improved biochemical, clinical progression-free survival, and overall survival in patients with high-risk pathological features according to published randomized trials. Offering immediate adjuvant RT to all men with high-risk pathological factors we are over-treating around 50% of patients who would anyway be cancer-free, exposing them to unnecessary toxicity and adding costs to the health-care system. The current dilemma is, thus, whether to deliver adjuvant immediate RT solely on the basis of high-risk pathology, but in the absence of measurable prostate-specific antigen, or whether early salvage radiotherapy would yield equivalent outcomes. Randomized trials are ongoing to definitely answer this question. Retrospective analyses suggest that there is a dose–response favoring doses >70 Gy to the prostate bed. The evidence regarding the role of androgen deprivation therapy is emerging, and ongoing randomized trials are underway.

Ultrasonographically Guided, Compartment-Oriented Lymph Node Dissection in the Management of Papillary Thyroid Cancer

Lymphatic metastases are common in papillary thyroid cancer (PTC) at the time of diagnosis [1]. In the presence of synchronous cervical lymphadenopathy, diagnosed clinically or ultrasonographically, the standard surgical approach has been the modified radical lymph node dissection (MRLND), performed at the time of initial total thyroidectomy. This strategy achieves optimal local control of the disease (thereby minimizing local recurrence rates), improves the efficacy of postoperative radioactive therapy (aiming to eradicate potential residual microscopic disease) and facilitates patient’s monitoring during follow-up by measuring serum thyroglobulin [2]. During recent decades, a modern classification of neck lymph nodes has been widely adopted, based on findings and landmarks from cross-sectional anatomic imaging; this is a useful aid in mapping nodal surgical intervention. This classification system is composed of six major nodal regions (levels or compartments I to VI) and defines a compartment-oriented neck dissection. Sublevel classification is also used when certain zones within the larger levels have independent biological significance [3]. Current evidence suggests specific patterns of lymphatic metastases in PTC. Central (compartment VI) lymph nodes are often the first site for lymphatic metastases from PTC, since this level is considered as the first lymphatic basin draining thyroid parenchyma. The most common lateral lymph node regions harboring metastases are levels III and IV [4,5]. Metastases to levels II and V are more rarely observed [6]. Finally, metastases to level I nodes are extremely rare in PTC [6,7]. Recent advances in imaging allow – with acceptable accuracy – the recognition of the presence of pathological lymph nodes within the different compartments of the neck. Currently, high-resolution ultrasonography (US) is being used extensively in the preoperative assessment of cervical lymph nodes (sensitivity 97%, specificity 93%) [8]. The US characteristics of a suspicious lymph node include increased size, round shape (short axis to long axis ratio ≥0.5), absent echogenic hilum, irregular margins, thickened hypoechoic cortex, intranodal calcifications, cystic necrosis, peripheral or mixed vascularity and increased elasticity score. The accuracy of US in recognizing pathologic neck lymph nodes is higher for the lateral nodal compartments, while US evaluation of central compartment lymph nodes has been proved to be of lower sensitivity in detecting metastatic lymph nodes especially in patients with coexistent chronic

Regional Nodal Radiotherapy in Early-Stage Breast Cancer: Where Are We in 2016?

The goal of locoregional treatment in early-stage breast cancer patients is to eradicate residual locoregional microscopic disease in order to maximize locoregional control, to minimize seeding of distant metastatic sites, and ultimately to improve overall survival. Recently published landmark randomized trials demonstrate that the addition of regional nodal radiotherapy to breast conserving therapy or mastectomy in node positive or high-risk node negative women not only improves locoregional control but also decreases distant metastasis with a trend towards improved overall survival with a favorable toxicity profile. Certain node-positive early-stage breast cancer patients, however, have low rates of axillary recurrence and high rates of breast cancer-specific survival even with sentinel lymph node excision alone without axillary lymph node dissection. Herein, we review the recent developments in regional nodal management and reconcile the apparent conflict between the surgical and radiotherapy literature. In this context, we provide guidance as to the patients appropriate for regional nodal radiotherapy in 2016 and highlight important treatment considerations to minimize long-term toxicity.

Limited Margin Radiation Therapy for Children and Young Adults With Ewing Sarcoma Achieves High Rates of Local Tumor Control

To determine the rate of local failure using focal conformal, limited margin radiation therapy (RT) and dose escalation for tumors ≥8cm (greatest dimension at diagnosis) in children and young adults with Ewing sarcoma (EWS). Eligible patients with EWS were treated on a phase 2 institutional trial of focal conformal, limited margin RT using conformal or intensity modulated techniques. The treatment volume incorporated a 1-cm constrained margin around the gross tumor. Unresected tumors, <8cm at diagnosis, received a standard dose of 55.8Gy and tumors ≥8cm, an escalated dose to 64.8Gy. Patients with microscopic residual disease after resection received adjuvant RT to 50.4Gy. Adjuvant brachytherapy was permitted in selected patients. Forty-five patients were enrolled: 26 with localized and 19 with metastatic disease. Median (range) age, tumor size, and follow-up were 13.0years (2.9-24.7years), 9.0cm (2.4-17.0cm), and 54.5months (1.9-122.2months), respectively. All patients received systemic chemotherapy. The median (range) RT dose for all patients was 56.1Gy (45-65.5 Gy). Seventeen patients received adjuvant, 16 standard-dose, and 12 escalated-dose RT. Failuresincluded 1 local, 10 distant, and 1 local/distant. The estimated 10-year cumulative incidence of local failure was 4.4%±3.1%, with no statistical difference seen between RTtreatment groups and no local failures in the escalated-dose RT treatment group. Treatment with focal conformal, limited margin RT, including dose escalation for larger tumors, provides favorable local tumor control in EWS.

Routine ureteric stenting before cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy in managing peritoneal carcinomatosis from gynecologic malignancies: a single-center experience.

Iatrogenic ureteric injury is a rare, yet serious operative complication in gynecologic procedures and associated with substantial morbidities such as prolonged hospitalization, additional financial-based ureter-related repairing procedures, impaired renal function, and compromised quality of life. Direct visual identification of ureters can be very challenging in managing patients with primary advanced or recurrent disseminated intraperitoneal gynecologic malignancies, who are referred to complex procedures such as cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). To report our single-center experience (feasibility and morbidity) with prophylactic ureteric stents as a routine practice before CRS+HIPEC procedure in managing peritoneal carcinomatosis (PC) from gynecologic malignancies. From June-2010 to March-2014, all patients with gynecologic-related PC, managed with CRS+HIPEC, and underwent prophylactic ureteric stents. The data were retrospectively abstracted and analyzed. Fifty-three patients were identified. Almost all PC cases were secondary/recurrence presentations (90.6%) and originated from ovarian cancer (84.9%). Optimal cytoreduction microscopic residual disease) was achieved in 35 patients (60%). Average insertion time of ureteric stents was 8.9±3.3min. Fifty-two patients (98.1%) received bilateral ureteric stents. Forty-nine patients (92.5%) had their ureteric stents removed by the end of procedure. No patient experienced major peri-operative urinary tract-related complications. Prophylactic ureteric stents appeared to be feasible, potentially safe, and could reduce the risk of iatrogenic ureteric injuries without incurring an increase in urinary tract-related complications. Prophylactic ureteric stenting does not eliminate the necessity for competent anatomical knowledge, meticulous retroperitoneal dissection and direct intra-operative visualization of ureters.

CD55 is a HIF-2α marker with anti-adhesive and pro-invading properties in neuroblastoma.

CD55 has been revealed to have an important role in tumor genesis, and presence of small populations of cells with strong CD55 expression would be sufficient to predict poor prognosis of several tumors. In our study we revealed that CD55 is a novel target of hypoxia-inducible factor HIF-2α in neuroblastoma (NB) cells. We show that HIF-2α expression is sufficient to sustain stem-like features of NB cells, whereas CD55 protein upon HIF-2α expression contributes to growth of colonies and to invasion of cells, but not to stemness features. Interestingly, in NB tissues, CD55 expression is limited to quite a small population of cells that are HIF-2α positive, and the gene expression of CD55 in the NB data set reveals that the presence of CD55high affects prognosis of NB patients. The functional characterization of CD55-positive populations within heterogeneous NB monoclonal cell lines shows that CD55 has pro-invading and anti-adhesive properties that might provide the basis for the ability of solid tumors to survive as microscopic residual disease. The easy accessibility to CD55 membrane antigen will offer the possibility of a novel antibody approach in the treatment of recurrent tumors and will provide a ready target for antibody-based visualization in NB diagnosis and prognosis.

Intraoperative diagnostics and elimination of residual microtumours with plasmonic nanobubbles.

Failure of cancer surgery to intraoperatively detect and eliminate microscopic residual disease (MRD) causes lethal recurrence and metastases, and the removal of important normal tissues causes excessive morbidity. Here, we show that a plasmonic nanobubble (PNB), a non-stationary laser pulse-activated nanoevent, intraoperatively detects and eliminates MRD in the surgical bed. PNBs were generated in vivo in head and neck cancer cells by systemically targeting tumours with gold colloids and locally applying near-infrared, low-energy short laser pulses, and were simultaneously detected with an acoustic probe. In mouse models, between 3 and 30 residual cancer cells and MRD (undetectable with current methods) were non-invasively detected up to 4 mm deep in the surgical bed within 1 ms. In resectable MRD, PNB-guided surgery prevented local recurrence and delivered 100% tumour-free survival. In unresectable MRD, PNB nanosurgery improved survival twofold compared with standard surgery. Our results show that PNB-guided surgery and nanosurgery can rapidly and precisely detect and remove MRD in simple intraoperative procedures.

Abstract P2-11-03: Phase I/II randomized study of combination immunotherapy with or without polysaccharide krestin (PSK) concurrently with a HER2 ICD peptide-based vaccine in patients with stage IV breast cancer receiving HER2-targeted monoclonal antibody therapy

Abstract Natural killer (NK) cell defects, commonly seen in metastatic breast cancer (MBC) lead to decrease in dendritic cell (DC) maturation, proinflammatory cytokine production, and tumor infiltrating T-cells (TILs). This results in a protumorigenic Th2 immune microenvironment with low response rates to immunotherapy (i.e., immune checkpoint blockade) and standard chemotherapy. PSK, a potent TLR-2 agonist, activates NK cells to produce IFN-γ and IL-12 and promote DC maturation/differentiation toward a Th1 profile in the tumor microenvironment which results in antigen specific TIL that can eradicate tumor. The combination immunotherapy of PSK and HER2 directed therapy described here, aims at inducing Th1 immunity and tumor specific T-cells. This proposed regimen could eradicate microscopic residual disease and prevent recurrence in optimally treated HER2+ MBC patients. Moreover, the regimen could result in enhanced trafficking of TILs to the site of tumor and improve the efficacy of checkpoint inhibitors and other therapies. A phase I/II randomized 2 arm study of combination immunotherapy with oral PSK (or placebo) given with a HER2 peptide vaccine and HER2 mAb therapy (trastuzumab (TZ) +/- pertuzumab (PZ)) was initiated to assess the safety of the approach and evaluate the effect of PSK on NK cell activity, pro-inflammatory cytokine/chemokine profile; and HER2 vaccine-induced T cell immunity. Methods: Up to 30 patients with HER2+ MBC who are without evidence of disease after definitive therapy and currently on maintenance TZ +/- PZ are enrolled and randomly assigned in equal numbers to 1 of 2 arms (15 patients/arm): Arm 1: HER2 ICD vaccine + placebo or Arm 2: HER2 ICD vaccine + PSK. All patients receive concomitant treatment with 4 months of daily oral PSK or placebo, 3 monthly intradermal HER2 ICD vaccinations and continued TZ +/- PZ. Toxicity is evaluated per CTEP CTCAE 4.0, during and post vaccination. Serial blood draws for immunologic evaluation of NK cell activity and antigen-specific T cell immunity via flow cytometry and IFN-γ ELISPOT, respectively; and pro-inflammatory cytokines/chemokines. Results: 24 subjects have been enrolled and 60 vaccines have been given. 16 subjects have completed all 3 vaccines and PSK/placebo; and 6 subjects are currently in progress. 2 subjects received &amp;lt; 3 vaccines and were taken off study. Of 144 reported adverse events (AEs), 97% were Grade 1-2; 66 (46%) were possibly, probably, or definitely related to study treatment. Most common AEs are injection site reaction and flu-like symptoms. There have been a total of four Grade 3 AEs, 1 episode of self-limited nausea/vomiting attributed to study treatment; and cognitive disturbance, fatigue, and lymphopenia all in 1 subject and attributed to disease progression. There have been no Grade 4 AEs. Immunologic analyses are ongoing and will be presented along with completed clinical data on all patients. Conclusion: Combination immunotherapy with PSK/placebo and concurrent HER2 directed therapy is safe and well-tolerated. Further ongoing immunologic studies will help define the immunogenicity of the approach. Citation Format: Salazar LG, Higgins D, Childs J, Coveler AL, Liao J, Stanton S, Gooley T, Standish LJ, Sasagawa M, DISIS ML. Phase I/II randomized study of combination immunotherapy with or without polysaccharide krestin (PSK) concurrently with a HER2 ICD peptide-based vaccine in patients with stage IV breast cancer receiving HER2-targeted monoclonal antibody therapy. [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 P2-11-03.

Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Methodology, Drugs and Bidirectional Chemotherapy.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) combined have been recognized as standard of care for treatment of a subset of patients with peritoneal carcinomatosis (PC). The aim of CRS is to eliminate all macroscopic disease through a series of visceral resections followed by targeting any residual microscopic disease with intraperitoneal chemotherapy, exposing the peritoneal surfaces to a high concentration of chemotherapy with a lower systemic toxicity. Different regimes of intraperitoneal chemotherapy include HIPEC, early postoperative intraperitoneal chemotherapy (EPIC) and bidirectional chemotherapy. The efficacy and modality of treatment with intraperitoneal chemotherapy is dependent on multiple factors including the chosen cytotoxic agent and its pharmacokinetics and pharmacodynamics. There is no standardized methodology for intraperitoneal chemotherapy administration. This review will discuss the pharmacological principles of the various intraperitoneal chemotherapy techniques.

Safety considerations for Health care Workers involved in Cytoreductive Surgery and Perioperative chemotherapy.

The combined modality treatment of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has gained worldwide acceptance for management of selected patients with peritoneal metastases from various cancers. Cytoreductive surgery is performed with the goal of removing all macroscopic disease and is coupled with perioperative chemotherapy (POC) in the form of HIPEC with or without EPIC (early postoperative intraperitoneal chemotherapy) to deal with the microscopic residual disease. These treatments entail the use of cytotoxic drugs in the operation theatre or in the intensive care unit where they are not commonly used and put the healthcare workers participating in the treatment at risk of exposure. CRS is performed with high voltage electrocautery generating a large amount of surgical smoke which is inhaled by the involved personnel and has potential health hazards. This article outlines the safety measures to be taken while performing CRS and POC.

Predictors of Survival in Esophageal Squamous Cell Carcinoma with Pathologic Major Response after Neoadjuvant Chemoradiation Therapy and Surgery: The Impact of Chemotherapy Protocols.

Tumor recurrence is an important problem threatening esophageal cancer patients after surgery, even when they achieve a pathologic major response (pMR) after neoadjuvant concurrent chemoradiation therapy (CCRT). The predictors related to overall survival and disease progression for these patients remain elusive. We aimed to identify factors that predict disease progression and overall survival in esophageal squamous cell carcinoma (SCC) patients who achieve a pMR after neoadjuvant CCRT followed by surgery. We conducted a retrospective study to analyze the factors influencing survival and disease progression after esophagectomy for esophageal cancer patients who had a major response to CCRT, which is defined by complete pathological response or microscopic residual disease without lymph node metastasis. From our study cohort, 285 patients underwent CCRT and subsequent esophagectomy; 171 (60%) of these patients achieved pMR. After excluding patients with lymph node metastases, incomplete clinical data, and adenocarcinomas, we enrolled 117 patients in this study. We found that the CCRT regimen was the only factor that influenced overall survival. The overall survival of the patients receiving taxane-incorporated CCRT was superior to that of patients receiving traditional cisplatin and 5-fluorouracil (PF) (P = 0.011). The CCRT regimen can significantly influence the clinical outcome of esophageal SCC patients who achieve pMR after neoadjuvant CCRT and esophagectomy. Incorporation of taxanes into cisplatin-based CCRT may be associated with prolonged survival.

Clinical Features of Metastatic Hepatic Malignancies.

The liver is a common site for gastrointestinal tumor metastases as it is the first major organ reached by blood draining the portal venous system. With the development of more effective chemotherapeutic agents which may eradicate residual microscopic disease in the liver and help reduce known tumor burden, partial hepatectomy to remove gross metastatic disease will likely become increasingly utilized in the future. This chapter discusses the presentation and clinical factors in liver directed surgical resection.

External-beam radiotherapy for differentiated thyroid cancer locoregional control: A statement of the American Head and Neck Society.

The use of external-beam radiotherapy (EBRT) in differentiated thyroid cancer (DTC) is debated because of a lack of prospective clinical data, but recent retrospective studies have reported benefits in selected patients. The Endocrine Surgery Committee of the American Head and Neck Society provides 4 recommendations regarding EBRT for locoregional control in DTC, based on review of literature and expert opinion of the authors. (1) EBRT is recommended for patients with gross residual or unresectable locoregional disease, except for patients <45 years old with limited gross disease that is radioactive iodine (RAI)-avid. (2) EBRT should not be routinely used as adjuvant therapy after complete resection of gross disease. (3) After complete resection, EBRT may be considered in select patients >45 years old with high likelihood of microscopic residual disease and low likelihood of responding to RAI. (4) Cervical lymph node involvement alone should not be an indication for adjuvant EBRT.

What Should We Expect After a Complete Cytoreduction at the Time of Interval or Primary Debulking Surgery in Advanced Ovarian Cancer?

To compare the impact, in terms of survival, of complete cytoreduction after primary debulking surgery (PDS) and interval debulking surgery (IDS) in patients with advanced ovarian cancer (International Federation of Gynecology and Obstetrics stages III-IV) by reviewing the recent literature. A search of the PubMed database during the last 7years (2008-2014) was carried out looking for studies specifically showing data on median survival or disease-free survival after complete cytoreduction after either PDS or IDS. We found 24 publications including 14,182 patients with stages III to IV ovarian cancer. A total of 11871 patients (83.7%) underwent PDS and 2311 (16.3%) underwent interval debulking after neoadjuvant chemotherapy. A total of 4684 patients (33%) were considered completely resected with microscopic residual disease. After PDS, the weighted average of median overall and progression-free survival was 43 and 17months, respectively, for the whole group. After IDS, median and progression-free survival were 33 and 14months. The rate of complete cytoreduction after PDS was inferior to the obtained in patients with IDS (27 vs. 59%). However, the median survival in patients with complete cytoreduction with primary cytoreduction was 23months longer than in the group with interval debulking (69 vs. 45months). Complete cytoreduction after IDS yields a inferior outcome in terms of median survival than PDS of almost 2years. Despite the higher rate of complete resection, IDS apparently fails to improve the results obtained by primary debulking.

Intraoperative electron radiation therapy combined with external beam radiation therapy and limb sparing surgery in extremity soft tissue sarcoma: a retrospective single center analysis of 183 cases

Background and purposeTo report our experience with limb-sparing surgery, IOERT and EBRT in extremity STS. Materials and methods183 patients were retrospectively analyzed. 78% presented in primary situation, with 80% located in the lower limb. Stage at presentation was: I: 6%, IIa: 25%, IIb: 21%, III: 42%, IV: 7%. The majority showed high-grade lesions (grade 1: 5%, 2: 31%, 3: 64%). IOERT was applied to the tumor bed (median 15Gy) and preceded (9%) or followed (91%) by EBRT (median 45Gy) in all patients. ResultsMedian follow-up was 64months (78months in survivors). Surgery was complete in 68%, while 32% had microscopic residual disease. 5- and 10-year-LC was 86% and 84%, respectively. LC was significantly higher in primary compared to recurrent disease and tended to be higher after complete resection. Estimated 5- and 10-year-DC was 68% and 66%, while corresponding OS was 77% and 66%, respectively. OS was significantly affected by grading and stage. Severe postoperative complications and late toxicities were observed in 19% and 20%, respectively. Limb-preservation rate was 95% with good function in 83%. ConclusionsCombination of limb-sparing surgery, IOERT and EBRT achieved encouraging LC and OS in this unfavorable patient group with acceptable postoperative complications and low rates of late toxicities resulting in a high limb-preservation rate and good functional outcome.

Surgical Management of Complicated Colon Cancer.

The management of complicated colon cancer (locally invasive, obstructed, or perforated cancers) can pose diagnostic and therapeutic challenges to surgical management. Adherence to traditional surgical oncologic principles must often be balanced with the patients' clinical presentation and other parameters. While the goal of an R0 (no residual microscopic disease) resection must always be kept in mind, situations sometimes arise which can make this difficult to achieve. Recognition of complicated disease and availability of varied therapeutic modalities is important to ensure favorable patient outcomes. This review will discuss the surgical management of complicated colon cancer, with special focus on locally advanced disease.

Impact of Positive Margins on Survival in Patients Undergoing Esophagogastrectomy for Esophageal Cancer

Multimodality treatment that includes esophagogastrectomy may represent the best option for curing accurately staged patients with esophageal cancer. We analyzed the impact of incomplete resection on outcomes after esophagogastrectomy for esophageal cancer. The incidence of positive margins for patients who underwent esophagogastrectomy without induction therapy for pathologic T1-3N0-1M0 esophageal cancer of the mid and lower esophagus from 2003 to 2006 in the National Cancer Database was analyzed with multivariate logistic regression. The impact of positive margins on survival was assessed using Kaplan-Meier and Cox proportional hazards analysis. Positive margins occurred in 342 of 3,125 patients (10.9%) who met study criteria. Increasing clinical T status was an independent predictor of positive margins in multivariate analysis, but the chance of positive margins decreased with larger facility case volumes. The presence of clinical nodal disease was not predictive of an incomplete resection. The 5-year survival of patients with positive margins (13.8%, 95% confidence interval [CI]: 10.5% to 18.1%) was significantly worse than that for patients with negative margins (46.3%, 95% CI: 44.4% to 48.3%, p < 0.001). Both microscopic residual disease (hazard ratio 1.37, 95% CI: 1.16 to 1.60, p < 0.001) and gross residual disease (hazard ratio 1.98, 95% CI: 1.62 to 2.42, p < 0.001) predicted worse survival in multivariate analysis of the entire cohort. Receiving adjuvant chemoradiation therapy slightly improved 5-year survival of patients with positive margins (16.9%, 95% CI: 11.3% to 23.6%, versus 13.5%, 95% CI: 9% to 20.3%, p < 0.001). Positive margins are associated with poor survival, and adjuvant therapy only marginally improved prognosis. Future studies are needed to better evaluate whether induction therapy can lower the incidence of positive margins.