Risk Factors For Local Recurrence Research Articles

Abstract P2-12-20: Rapid evaporative ionisation mass spectrometry towards real time intraoperative oncological margin status determination in breast conserving surgery

Abstract Introduction: Positive tumour margins following attempted breast conserving surgery (BCS) is an important risk factor for local recurrence. Nationally in the United Kingdom on average approximately 25% of patients undergoing BCS require additional surgery for positive margins. Traditional techniques such as specimen xray, frozen section & imprint cytology to optimise margin clearance have significant limitations. Various research methods under investigation include optical spectroscopy, high resolution imaging and radiofrequency spectroscopy. Rapid Evaporative Ionisation Mass Spectrometry (REIMS) is a new method that uses mass spectrometric analysis of the tissue specific ionic content of the surgical diathermy smoke plume for the rapid identification of dissected breast tissues as an intelligent knife (iKnife). We investigate the ability of the "iKnife" to analyze heterogeneous breast tissue intraoperatively using mass spectrometric techniques. Method: The study involved three stages that comprised: method development, tissue specific ex-vivo database construction and intraoperative analysis. Smoke aerosol produced as a result of electrosurgical diathermy from a variety of frozen, fresh and in-vivo breast samples were aspirated into a mass spectrometer via a modified surgical handpiece. Tissue diagnosis was confirmed by subsequent histopathological validation. The data underwent computational analysis using multivariate statistics –predominantly Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA), along with leave one patient out cross-validation. A total of 128 patients (n=40 method development, n=66 ex-vivo database, n=22 intraoperative analysis) undergoing breast surgery were enrolled in this study. Ethical approval was obtained from the Research Ethics Committee. Results: 40 patients contributed breast samples (normal and cancerous) for method optimisation to enable analysis of high intensity spectra from heterogeneous breast tissue. Following optimisation an ex-vivo database was constructed from 89 excised fresh breast tissue samples from 66 patients using 330 spectra (246 Normal, 60 Tumour – IDC, ILC, IMC and 24 Benign - fibroadenoma). Multivariate statistical analysis of data revealed classification of tumour compared to normal tissue with sensitivities of 93.0% and specificity of 91.9%. The iKnife was used intraoperatively during the entire operation of 25 surgeries. Spectral data was obtained within 1-2 seconds. Specific margin analysis correctly identified negative margins in 10 cases. Conclusions: The iKnife has been successfully developed for analysis of intraoperative heterogeneous breast tissue. Preliminary data suggests that this technique is suitable with high accuracy for the separation of normal, benign (fibroadenoma) and cancerous (invasive ductal and invasive lobular carcinoma) breast tissues. In comparison to the normal breast, cancerous tissues exhibit statistically different spectral profiles. Further work is aimed at the development of a real time algorithm able to match intraoperative data with the pre-existing database for the rapid interpretation and real time feedback of intraoperative data towards detecting positive margins intraoperatively. Citation Format: St John ER, Al-Khudairi R, Balog J, Rossi M, Gildea L, Speller A, Ramakrishnan R, Shousha S, Takats Z, Leff DR, Darzi A. Rapid evaporative ionisation mass spectrometry towards real time intraoperative oncological margin status determination in breast conserving surgery. [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 P2-12-20.

Abstract P3-13-06: The efficacy and long term results of intraoperative frozen section analysis to access resection margin in ductal carcinoma in situ

Abstract Introduction Breast conserving surgery (BCS) is a standard procedure for early breast cancer and resection margin state is the most important risk factor of local recurrence. Re-operation is generally conducted in 20∼40% after initial BCS to achieve negative margins, especially in breast cancer with carcinoma in situ components. In this study, we analyzed the long-term follow up results and efficacy of BCS using intraoperative frozen section analysis to access resection margin in ductal carcinoma in situ (DCIS) patients. Methods Between 2004 and 2006, 1016 patients were diagnosed with primary breast cancer and received breast cancer surgery. Among them, BCS was attempted as an initial operation for 523 patients. Superior, inferior, medial and lateral margin of resected specimen were evaluated according to the intraoperative frozen section analysis. If tumor cells existed less than 2mm from resected specimen margin, intraoperative further resection was done and if the further resection was impossible, initial BCS was converted to mastectomy. All medical records and pathologic reports were reviewed retrospectively. Results Of the 523 patients who had to undergo BCS, 13.3% (70/523) were converted to mastectomy during initial BCS. The number of the patients who had either only DCIS or invasive carcinoma c carcinoma in situ component was 372 (71.1%, 372/523) and 17.2% (64/372) were converted to mastectomy. One hundred fifty one (28.9%, 151/523) patients had only invasive carcinoma and 3.97% (6/151) were converted to mastectomy. In this study, we analyzed 94 patients who had to undergo BCS with DCIS. The rate of intraoperative conversion to mastectomy was 13.8% (13/94) and 81 patients had successful BCS with 0∼3 times of intraoperative frozen section analysis. There were no differences between patients who had BCS and final mastectomy in clinicopathologic characteristics such as physical examination of tumor, age of patients, DCIS subtypes, nuclear polymorphism, presence of necrosis, ER, PR, HER2 and Ki67. After permanent biopsy was reported, in 5 patients, resected specimen had tumor cells within less than 2mm from resected margin, not inked margin. They had no reoperations and no recurrences. Mean follow up period was 76.6 months. One locoregional and 3 local recurrences in BCS patients and 1 local recurrence in mastectomy patients were found. There was no difference in disease free survival between two groups (95.1% vs 92.3%, p=0.659). In these DCIS patients, reoperation rate was 0%. Conclusion Intraoperative frozen section analysis during BCS to access resection margin helps to avoid reoperations and increase intraoperative success rate of BCS in DCIS. It also shows oncological safe long term results. Further studies are needed to resolve the problem with cost-effectiveness of intraoperative frozen section analysis. Citation Format: Choi JE, Yeu KJ, Park JY, Kang SH, Lee SJ, Bae YK. The efficacy and long term results of intraoperative frozen section analysis to access resection margin in ductal carcinoma in situ. [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 P3-13-06.

Abstract PL1: Critical Decision Making in Radiation Therapy for Breast Cancer in 2015

Abstract In 2005, the EBCTCG meta-analysis demonstrated for the first time that RT after either breast-conserving surgery (BCS) or mastectomy not only reduced local-regional recurrence (LRR), but also improved long-term survival. At the time, they (erroneously) postulated that for every 4 LRR's avoid at 5 years, there was an additional survivor at 15 years. The EBCTCG subsequently adopted 'any first recurrence' as the primary endpoint for the effect of RT based on 1 – RT's established systemic effect in reducing both local and distant recurrence, 2 – that time to LRR is not strictly valid, and 3 – that the ratio between reduction in LRR and improvement in survival no longer held up. The new 'ratio' is that for every 1.5 first recurrences avoided at 10 years, there is an additional survivor at 20 years. Over the last several decades, there has been a substantial reduction in local recurrence (LR) after BCS and RT. In series of patients treated in the 1970's, 5-year rate of LR was about 10% and in more recent series, it is about 2%. This decrease is attributable to 1 – improved mammographic evaluation, 2 – improved pathologic evaluation, and probably most importantly, 3 – the benefit seen with the addition of adjuvant systemic therapy. Also, over this time frame, risk factors for LR evolved with approximated subtype using ER, PR, HER2 status and either grade or Ki-67 now the main risk factor. 5-year LR is 6% for triple negative cancers and only about 1% for Luminal A cancers. Finally, hypofractionated breast irradiation has been established as at least equal to conventional fractionation. Updated EBCTCG results show consistent proportional benefits for RT after either BCS or mastectomy although the absolute benefit is quite small in many subgroups. The addition of RT to BCS improves 15-year mortality by 8.5% in node-positive patients, but only 3.3% in node-negative patients. Additionally, in the context of routine adjuvant systemic therapy, breast tangential irradiation (that treats much of the lower axilla) is sufficient to avoid regional recurrence if only 1 or 2 sentinel nodes are involved obviating the need for cALND. Also, there is evidence that internal mammary node and supraclavicular irradiation can improve 10-year disease-free survival in some patients treated with ALND. Critical issues currently include: 1. Which patients can be spared RT after BCS? The CALGB has established hormonal therapy alone as a reasonable option in patients aged > 70 years with largely low-grade, node-negative, ER+ breast cancer. Efforts are underway to identify additional ER+ patients who can be adequately managed by hormonal therapy alone. We are testing this approach in patients aged 50-75 with node-negative Luminal A cancers as determined by the Prosigna PAM-50 assay. 2. Which patients can be treated with hypofractionated RT? Available evidence is that it is nearly all patients getting breast tangents assuming adequate dose homogeneity. 3. In patients with 1 or 2 + SN's, should they receive high tangents (per Z-11) or full axillary and SC irradiation (per MA.20)? No easy answer, but one can use MD Anderson nomogram to estimate likelihood of + nSN's. If this is < 25-30%, consider high tangents. If the primary is in the inner quadrant, it seems prudent to contour the IMN's for possible inclusion. Citation Format: Harris JR. Critical Decision Making in Radiation Therapy for Breast Cancer in 2015. [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 PL1.

Abstract P5-17-08: Study of boost radiotherapy's influence on local control in 646 pure ductal carcinoma in situ breast cancer with long-term follow-up

Abstract BACKGROUND: Boost radiotherapy (B-RT) improves outcome in patients (pts) with invasive breast cancer. It's use in patients with pure ductal carcinoma in situ (DCIS) is unclear. There are two ongoing randomize trials, results are expected in ten years. Twelve retrospective observational studies have been published since 2006, the recent meta-analysis, support boost in the presence of positive margins. PATIENTS and METHODS: We analyse a retrospective women's cohort of 646 pure DCIS patients (pts) treated mainly in two Hospitals (n=518) from 1993 to 2014. The other ten Hospitals included 128 pts all 2005 long. Proportions were compared by boost status, using the chi-square tests. The impact of boost radiation on the development of local recurrence (LR) was determined using survival analyses. In the comparison of Kaplan-Meier (K-M) was used log-rank test. RESULTS: B-RT subgroup is 394 pts (61%), noB-RT 252 (39%). Median follow-up (FU) is 8.8 years. High risk factors: young age, size, margin status and tamoxifen (TMX) show differences among B-RT (p<0.05). 46% were Estrogen Receptor positive (ER+), 30% B-RT and 16% noB-RT. 22% RE+ in B-RT take TMX vs 9.4 % RE+ noB-RT. Total LR 65 (10%). In situ LR 30 pts (4,6%) and Invasive (Inv) 35 (5,4%). By subgroup, LR in B-RT 47 (12%) vs. 18 (7%) in noB-RT. By subtype, In situ LR in B-RT 20 (5.1%) vs. noB-RT 10 (4%). Inv LR in B-RT 27 (6.9%) vs. noB-RT 8 (3.2%). In uni & multivariate analysis, tumour size, Re-Excision, and TMX, are significant LR risk factors (p<0.05). Boost total doses >16 Gy in the B-RT subgroup is a LR significant risk factor related to 10-16 Gy (p∼0.05). TMX and Dose Boost are related (p<0.001). When Dose is introduced in multivariate analysis model, TMX lost signification. Contralateral local recurrence (CLR) in 29 pts (7%). Second tumours 9 pts (NSD between subgroups). Global disease free survival (DFS) is 80.5%, 77% in B-RT vs. 85% in noB-RT. Four pts have a LR combined with CLR; 2 pts have a LR and a second tumor; 1 pt with CLR and second tumour; 1 pt a Inv regional recurrence; 1 pt mixosarcoma in ipsilateral breast and lung metastases. Deaths: 3 pts (0.5%) after an Inv LR; 3 pts (0.5%) after Inv CR; 20 pts other causes; 10 pts lost their FU. Median FU in B-RT subgroup was 9y vs. 8.3y in noB-RT. The maximum FU according LR in B-RT is 20.6y vs. 17.4y in noB-RT. RL is not significant according to Boost (K-M p=0.398). Median LR in situ or inv depending of B-RT vs. noB-RT shows NSD (p=0.663). CONCLUSIONS: In this large cohort retrospective study with long-term follow-up B-RT was associated with similar LR as noB-RT despite being used more frequently with higher risk disease. Dose boost >16 Gy has a protective effect. Tamoxifen and boost dose are related variables. Further evidence, based on ongoing randomized trials results is essential. Citation Format: Cambra MJ, Moreno F, Sanz X, Anglada L, Moià M, Reyes V, Arenas M, Pedro A, Ballester R, García V, Sanjosé S, Cusidó M, Jimenez C, Macià M, Solé JM, Farrus B. Study of boost radiotherapy's influence on local control in 646 pure ductal carcinoma in situ breast cancer with long-term follow-up. [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 P5-17-08.

Extralevator Abdominoperineal Excision for Low Rectal Cancer--Extensive Surgery to Be Used With Discretion Based on 3-Year Local Recurrence Results: A Registry-based, Observational National Cohort Study.

Objectives:The aim of this prospective registry-based population study was to investigate the efficacy of extralevator abdominoperineal excision (ELAPE) regarding local recurrence rates within 3 years after surgery.Background:Local recurrence of rectal cancer is more common after abdominoperineal excision (APE) than after anterior resection. Extralevator abdominoperineal excision was introduced to address this problem. No large-scale studies with long-term oncological outcomes have been published.Methods:All Swedish patients operated on with an APE and registered in the Swedish ColoRectal Cancer Registry 2007 to 2009 were included (n = 1397) and analyzed with emphasis on the perineal part of the operation. Local recurrence at 3 years was collected from the registry.Results:The local recurrence rates at 3 years [median follow-up, 3.43 years (APE, 3.37 years; ELAPE, 3.41 years; not stated: 3.43 years)] were significantly higher for ELAPE compared with APE (relative risk, 4.91). Perioperative perforation was also associated with an increased risk of local recurrence (relative risk, 3.62). There was no difference in 3-year overall survival between APE and ELAPE. In the subgroup of patients with very low tumors (≤4 cm from the anal verge), no significant difference in the local recurrence rate could be observed.Conclusions:Extralevator abdominoperineal excision results in a significantly increased 3-year local recurrence rate as compared with standard APE. Intraoperative perforation seems to be an important risk factor for local recurrence. In addition to significantly increased 3-year local recurrence rates, the significantly increased incidence of wound complications leads to the conclusion that ELAPE should only be considered in selected patients at risk of intraoperative perforation.

A Prospective Outcomes Study of Proton Therapy for Chordomas and Chondrosarcomas of the Spine

To evaluate the effectiveness of definitive or adjuvant external beam proton therapy on survival in patients with chordomas and chondrosarcomas of the spine. Between March 2007 and May 2013, 51 patients with a median age of 58 years (range, 22-83 years) with chordoma (n=34) or chondrosarcomas (n=17) of the sacrum (n=21), the cervical spine (n=20), and the thoracolumbar spine (n=10) were treated with external beam proton therapy to a median dose of 70.2 Gy(RBE) [range, 64.2-75.6 Gy(RBE)] at our institution. Distant metastases, overall survival, cause-specific survival, local control, and disease-free survival were calculated. The mean follow-up time was 3.7 years (range, 0.3-7.7 years). Across all time points, 25 patients experienced disease recurrence: 18 local recurrences, 6 local and distant recurrences, and 1 distant metastasis. The 4-year rates of overall survival and cause-specific survival were 72%; disease-free survival was 57%, local control was 58%, and freedom from distant metastases was 86%. The median time to local progression was 1.7 years (range, 0.2-6.0 years), and the median time to distant progression was 1.6 years (range, 0.2-6.0 years). The risk factors for local recurrence were age ≤58 years (62% vs 26%; P=.04) and recurrence after prior surgery (29% vs 81%; P=.01). Secondary cancers developed in 2 patients: B-cell lymphoma 5.5 years after treatment and bladder cancer 2 years after treatment. We observed the following toxicities: sacral soft tissue necrosis requiring surgery (n=2), T1 vertebral fracture requiring fusion surgery (n=1), chronic urinary tract infections (n=1), surgery for necrotic bone cyst (n=1), and grade 2 bilateral radiation nephritis (n=1). High-dose proton therapy controls more than half of spinal chordomas and chondrosarcomas and compares favorably with historic photon data. Local progression is the dominant mode of treatment failure and may be reduced by treating patients at the time of initial diagnosis. The impact of age is a novel finding of this study.

Patient Prognostic Score and Associations With Survival Improvement Offered by Radiotherapy After Breast-Conserving Surgery for Ductal Carcinoma In Situ: A Population-Based Longitudinal Cohort Study.

Radiotherapy (RT) after breast-conserving surgery (BCS) is a standard treatment option for the management of ductal carcinoma in situ (DCIS). We sought to determine the survival benefit of RT after BCS on the basis of risk factors for local recurrence. A retrospective longitudinal cohort study was performed to identify patients with DCIS diagnosed between 1988 and 2007 and treated with BCS by using SEER data. Patients were divided into the following two groups: BCS+RT (RT group) and BCS alone (non-RT group). We used a patient prognostic scoring model to stratify patients on the basis of risk of local recurrence. We performed a Cox proportional hazards model with propensity score weighting to evaluate breast cancer mortality between the two groups. We identified 32,144 eligible patients with DCIS, 20,329 (63%) in the RT group and 11,815 (37%) in the non-RT group. Overall, 304 breast cancer-specific deaths occurred over a median follow-up of 96 months, with a cumulative incidence of breast cancer mortality at 10 years in the weighted cohorts of 1.8% (RT group) and 2.1% (non-RT group; hazard ratio, 0.73; 95% CI, 0.62 to 0.88). Significant improvements in survival in the RT group compared with the non-RT group were only observed in patients with higher nuclear grade, younger age, and larger tumor size. The magnitude of the survival difference with RT was significantly correlated with prognostic score (P < .001). In this population-based study, the patient prognostic score for DCIS is associated with the magnitude of improvement in survival offered by RT after BCS, suggesting that decisions for RT could be tailored on the basis of patient factors, tumor biology, and the prognostic score.

Metastasectomy or radiofrequency ablation for treatment for colorectal cancer liver metastasis: Comparison of recurrence rates and identification of risk factors for local recurrence.

769 Background: Metastasectomy and radiofrequency ablation (RFA) are currently use for treatment of colorectal cancer (CRC) liver metastasis aiming for total tumor ablation with sparing liver parenchyma. Literature is lacking of studies comparing results and risk of recurrence between both techniques. We aim to compare recurrence rate after RFA and metastasectomy for CRC liver metastasis and to define which lesion is the best candidate for each treatment. Methods: By a lesion-by-lesion analysis, we reviewed 121 metastases treated by metastasectomy (43 patients, median follow up 798 days) and 110 metastases treated by RFA (60 patients, median follow up 590 days). Rate of local recurrence (LR) and hepatic recurrence (HR) were compared. We analyzed patients and primary tumor characteristics, looked for predictive factors for recurrence in metastasis data: size, deepness in liver, distance to hepatic veins, pathological resection margins in case of surgery. Analysis were performed using Chi Square and logistic regression in uni and multivariate analysis. Results: Patients and primary tumor characteristics were similar. Metastasis size was larger in metastasectomy group (18mm, range 2-90mm and 15mm, range 3-55mm; p = 0.03). Lesions were located deeper in the liver parenchyma in RFA group (20mm, range 3-51mm and 26mm, range 6-59mm; p &lt; 0.001). Rate of LR and HR were nearly statistically different in favor of RFA: LR was 19% for metastasectomy group and 10% for RFA group (p = 0.06, delay: 245 and 289 days, p = 0.56), HR were 78% for metastasectomy and 66% for RFA (p = 0.054, delay: 226 and 235 days, p = 0.81). Predictive factors for recurrence in metastasectomy group: R1 status (p = 0.03) and metastasis deepness (p = 0.02). Metastasis deepness and proximity to hepatic veins increased risk for R1 (p = 0.04 and p &lt; 0.001 respectively). We found no predictive factor for recurrence in RFA group. Conclusions: Pending proper selection (small lesions visible under imaging guidance), RFA tends to have a lower recurrence rate than metastasectomy. Lesions localized in depth in the liver parenchyma, close to hepatic veins are at risk of LR after metastasectomy.

Impact of tumor location on local recurrence after nephroureterectomy for upper tract urothelial carcinoma: Implications for adjuvant radiotherapy.

390 Background: To date, risk factors for local recurrence after complete removal of upper tract urothelial carcinoma (UTUC) have not been clearly identified. We evaluated the impact of tumor location on local recurrence in UTUC patients underwent radical nephroureterectomy. Methods: Among UTUC patients who underwent radical nephroureterectomy between 1998 and 2012, 192 (54.4%) patients with renal pelvic tumor and 161 (45.6%) patients with ureter tumor were included. Local recurrence was divided into regional lymph node recurrence (LNR) and surgical bed recurrence (SBR). The significance of tumor location and other variables on local recurrence were evaluated. Results: Lymphovascular invasion (p = 0.003), carcinoma in situ (p = 0.006) and high grade tumor (p &lt; 0.001) were more common in ureter tumor. During median follow-up period of 73 months, local recurrence was occurred in 33 (9.3%) patients. Among subtype of local recurrence, SBR (8.1 vs. 2.1%, p = 0.011) were more common in patients with ureter tumor compared to renal pelvic tumor although the probability of regional LNR was not significantly different according to tumor location (7.5% vs. 3.1%, p = 0.088). 5-year local recurrence-free survival (80.5% vs. 94.2%, p = 0.002), LNR-free survival (89.8 vs. 96.5%, p = 0.046) and SBR-free survival (88.3% vs. 97.6%, p = 0.005) were inferior in ureter tumor compared to renal pelvic tumor. Ureter tumor (HR; 2.552, p = 0.017), high grade tumor (HR; 3.064, p = 0.016) and advanced tumor stage (≥T3) (HR; 3.236, p = 0.002) were associated with local recurrence. Ureter tumor (HR; 4.704, p = 0.002) and advanced tumor stage (HR; 4.840, p = 0.006) were risk factors for SBR. However, tumor location was not associated with LNR although lymphovascular invasion (HR; 5.451, p &lt; 0.001) and high grade tumor (HR; 4.191, p = 0.012) were related with LNR. Conclusions: Ureter located tumor was associated with local recurrence which comes from the SBR. Adjuvant radiotherapy or surgical technique for reducing the risk of SBR should be considered in patients with ureter tumor.

Sphincter-Sparing Surgery in Patients with Mid and Low Rectal Cancer - Risk Factors for Local Recurrence and Anastomotic Leakage.

The purpose of this article is to identify the risk factors for local recurrence and anastomotic leakage after sphincter-sparing surgery for low and mid rectal cancer. Material and Methods: We prospectively analyzed a group of 38 patients with low and middle rectal cancer who underwent sphincter-sparing surgery. Low anterior resection was performed in 32 cases (84.2%) and 6 cases (15.8%) benefited of ultralow anterior resection. Clinical stadialization cTNM included 3 patients (7.9%) T1 stage, 11 patients (28.9%) T2 stage and 24 patients (63.2%) T3 stage. Preoperative radiotherapy was performed in 33 cases (86.4%), and chemotherapy was associated in 20 cases (52.6%). Results: The stages I and II cancers were prevalent (63.2%), followed by stage III cancers (23.7%) and stage IV cancers (13.2%). The rate of complications of 52.6% (20 cases) was associated with T3 stage cancers. Anastomotic leakage has occurred in 4 cases (10.5%) and tumor recurrence has developed in 3 cases (7.9%). The rate of local recurrence and anastomotic leakage is associated with the number of positive lymph nodes (more than 4 nodes, 5.3%, p = 0.023). We found no association between chemoradiotherapy and the risk of local recurrence (p 0.05). Other postoperative complications included intestinal obstruction by adhesions or bowel volvulus (5 cases, 13.2%), postradiation colitis (3 cases, 7.7%), coloanal anastomotic stenosis (1 case, 2.6%), rectovaginal fistula (1 case, 2.6%), ileostomy bleeding (1 case, 2.6%), wound infection (2 cases, 5.3%). Conclusions: Risk factors associated with local recurrence and anastomotic leakage are aggressive stage tumor, lymphnodes involvement, neoadjuvant therapy and postoperative anemia. The postoperative outcome was favorable after sphincter preservation surgery and the absence of definitive colostomy had an important impact on the quality of life of the patients with distal rectal cancer.

Risk factors for local recurrence after en bloc endoscopic submucosal dissection for early gastric cancer.

To investigate factors related to recurrence following en bloc resection using endoscopic submucosal dissection (ESD) in patients with early gastric cancer (EGC). A total of 1121 patients (1215 lesions) who had undergone ESD for gastric neoplasia between April 2003 and May 2010 were retrospectively reviewed. Data from 401 patients (415 lesions) were analyzed, following the exclusion of those who underwent piecemeal resection, with deep resection margin invasion or lateral margin infiltration, and diagnosed with benign lesions. Local recurrence after en bloc ESD was found in 36 cases (8.7%). Unclear resection margins, long procedure times, and narrow safety margins were identified as risk factors for recurrence. Lesions located in the upper third of the stomach showed a higher rate of recurrence than those located in the lower third of the stomach (OR = 2.9, P = 0.03). The probability of no recurrence for up to 24 mo was 79.9% in those with a safety resection margin ≤ 1 mm and 89.5% in those with a margin > 1 mm (log-rank test, P = 0.03). Even in cases in which en bloc ESD is performed for EGC, local recurrence still occurs. To reduce local recurrences, more careful assessment will be needed prior to the implementation of ESD in cases in which the tumor is located in the upper third of the stomach. In addition, clear identification of tumor boundaries as well as the securing of sufficient safety resection margins will be important.

Long-Term Outcome and Surveillance Colonoscopy after Successful Endoscopic Treatment of Large Sessile Colorectal Polyps.

PurposeAlthough there is a consensus about the need for surveillance colonoscopy after endoscopic resection, the interval remains controversial for large sessile colorectal polyps. The aim of this study was to evaluate the long-term outcome and the adequate surveillance colonoscopy interval required for sessile and flat colorectal polyps larger than 20 mm.Materials and MethodsA total of 204 patients with large sessile and flat polyps who received endoscopic treatment from May 2005 to November 2011 in a tertiary referral center were included.ResultsThe mean age was 65.1 years and 62.7% of the patients were male. The mean follow-up duration was 44.2 months and the median tumor size was 25 mm. One hundred and ten patients (53.9%) received a short interval surveillance colonoscopy (median interval of 6.3 months with range of 1-11 months) and 94 patients (46.1%) received a long interval surveillance colonoscopy (median interval of 13.6 months with range of 12-66 months). There were 14 patients (6.9%) who had local recurrence at the surveillance colonoscopy. Using multivariate regression analysis, a polyp size greater than 40 mm was shown to be independent risk factor for local recurrence. However, piecemeal resection and surveillance colonoscopy interval did not significantly influence local recurrence.ConclusionEndoscopic treatment of large sessile colorectal polyps shows a favorable long-term outcome. Further prospective study is mandatory to define an adequate interval of surveillance colonoscopy.

Endoscopic mucosal resection of colorectal adenomas > 20 mm: Risk factors for recurrence.

To evaluate risk factors for local recurrence after endoscopic mucosal resection of colorectal adenomas > 20 mm. Retrospective data analysis of 216 endoscopic mucosal resections for colorectal adenomas > 20 mm in 179 patients (40.3% female; median age 68 years; range 35-91 years). All patients had at least 1 follow-up endoscopy with a minimum control interval of 2 mo (mean follow-up 6 mo/2.0-43.4 mo). Possible factors associated with local recurrence were analyzed by univariate and multivariate analysis. Median size of the lesions was 30 mm (20-70 mm), 69.0% were localized in the right-sided (cecum, ascending and transverse) colon. Most of the lesions (85.6%) showed a non-pedunculated morphology and the majority of resections was in piecemeal technique (78.7%). Histology showed carcinoma or high-grade intraepithelial neoplasia in 51/216 (23.6%) lesions including 4 low risk carcinomas (pT1a, L0, V0, R0 - G1/G2). Histologically proven recurrence was observed in 33/216 patients (15.3%). Patient age > 65 years, polyp size > 30 mm, non-pedunculated morphology, localization in the right-sided colon, piecemeal resection and tubular-villous histology were found as associated factors in univariate analysis. On multivariate analysis, only localization in the right-sided colon (HR = 6.842/95%CI: 1.540-30.394; P = 0.011), tubular-villous histology (HR = 3.713/95%CI: 1.617-8.528; P = 0.002) and polyp size > 30 mm (HR = 2.563/95%CI: 1.179-5.570; P = 0.017) were significantly associated risk factors for adenoma recurrence. Meticulous endoscopic follow-up is warranted after endoscopic mucosal resection of adenomas localized in the right-sided colon larger than > 30 mm, with tubular-villous histology.

The impact of anastomotic leakage on oncologic outcomes and the receipt and timing of adjuvant chemotherapy after colorectal cancer surgery

PurposesTo evaluate the impact of anastomotic leakage on oncologic outcomes in patients with colorectal cancer. We also evaluated the influence of anastomotic leakage on receipt and commencement time of adjuvant chemotherapy. MethodsA total of 809 consecutive patients undergoing major resection for colorectal cancer were categorized into leak (n = 33, 4.1%) and non-leak (n = 776, 95.9%) groups. ResultsThe 5-year local recurrence rates of stage II disease were 0.6% and 20.0% for non-leak and leak groups respectively (p = 0.046), and the equivalent rates for stage III disease were 9.1% and 59.4% respectively (p < 0.001). For stage III disease, receipt of adjuvant therapy was lower in the leak group (63% vs. 87%, p = 0.007) and mean time to initiation of chemotherapy was longer in the leak group (52 days vs. 37 days) but this did not reach statistical significance (p = 0.080). Older age (hazard ratio [HR] = 2.8), advanced TNM classification (HR = 3.6), and anastomotic leakage (HR = 8.9) were adverse risk factors for local recurrence based on multivariate analysis. ConclusionsAnastomotic leakage adversely influenced local recurrence rates in stage II and III disease and was an independent risk factor for local recurrence. Additionally, anastomotic leakage contributed to failure to receive adjuvant chemotherapy in patients with stage III disease.

Hypofractionated irradiation in elderly patients with breast cancer after breast conserving surgery and mastectomy : Analysis of 205 cases.

BackgroundSeveral randomized trials and meta-analyses confirmed a wide benefit of radiotherapy (RT), both after breast conserving surgery (BCS) and mastectomy. However, many elderly women don't receive RT. Hypofractionated (HF) RT allows « simplified » and more accessible treatments with equivalent results to classic RT in three large randomized trials. However, there are few available data on HF-RT for nodal irradiation, as well as for the boost.MethodsWe evaluated patients treated for IBC by HF-RT between 2004 and 2012 in two regional cancer centres. We used an original scheme delivering 45 Gy in 15 fractions three times a week, both after BCS or mastectomy, with or without nodal irradiation. After BCS, a 9 Gy boost in 3 fractions was delivered. Local, regional and distant recurrences were assessed, as well as acute and late cutaneous, cardiac or pulmonary toxicities.Results205 patients were analysed, 116 after BCS (57 %) and 89 after mastectomy (43 %). Median age was 81 years (range: 52-91); 44 % had axillary nodal involvement (pN+). The Nottingham Prognostic Index (NPI) scored 0, 1, 2 and 3 in 10 %, 27 %, 44 % and 19 % of the cases. A nodal HF-RT was delivered in 65 patients (32 %) and boost in 98 patients (84 % of BCS) by 9 Gy/3 fr scheme. Fifty (24 %) patients underwent chemotherapy and 156 (75 %) hormonal treatment.With a 49-month median follow-up, 3/116 (2.6 %) patients and 4/89 (4.5 %) had local recurrence (LR) after BCS and mastectomy, respectively. The overall 5-year LR rate was 4.4 %. In univariate and multivariate analysis, LR risk factors were: high NPI (HR 5.46; p = 0.028), and triple negative tumour (HR 9.78; p = 0.006). Only 8 (4.5 %) patients had grade III skin toxicity; 29 (14 %) late fibrosis and 16 (8 %) telangiectasia. No pulmonary or cardiac toxicity was observed.ConclusionOur HF-RT scheme (with or without nodal irradiation) confirms in elderly patients the data from randomized trials, both after BCS or mastectomy. Toxicity seems very acceptable but requires a longer follow-up. A larger evaluation is still ongoing in several other centres in France.

Prognostic Factors for Local, Loco-regional and Systemic Recurrence in Early-stage Breast Cancer.

Aim: The risk of recurrence in breast cancer depends on factors such as treatment but also on the intrinsic subtype. We analyzed the risk factors for local, loco-regional and systemic recurrence, evaluated the differences and analyzed the risk of recurrence for different molecular subtypes. Material and Methods: A total of 3054 breast cancer patients who underwent surgery followed by adjuvant treatment at HSK hospital or Essen Mitte Hospital between 1998 and 2011 were analyzed. Based on immunohistochemical parameters, cancers were divided into the following subgroups: luminal A, luminal B (HER2-), luminal B (HER2+), HER2+ and TNBC (triple negative breast cancer). Results: 67 % of tumors were classified as luminal A, 13 % as luminal B (HER2-), 6 % as luminal B (HER2+), 3 % as HER2+ and 11 % as TNBC. After a median follow-up time of 6.6 years there were 100 local (3.3 %), 32 loco-regional (1 %) and 248 distant recurrences (8 %). Five-year recurrence-free survival for the overall patient collective was 92 %. On multivariate analysis, positive nodal status, TNBC subtype and absence of radiation therapy were found to be independent risk factors for all forms of recurrence. Age < 50 years, tumor size, luminal B (HER2-) subtype and breast-conserving therapy were additional risk factors for local recurrence. Compared to the luminal A subtype, the risk of systemic recurrence was higher for all other subtypes; additional risk factors for systemic recurrence were lymphatic invasion, absence of systemic therapy and mastectomy. Conclusion: Overall, the risk of local and loco-regional recurrence was low. In addition to nodal status, subgroup classification was found to be an important factor affecting the risk of recurrence.

Neoadjuvant proton beam irradiation followed by transscleral resection of uveal melanoma in 106 cases

AimsTo describe results after neoadjuvant proton beam irradiation followed by transscleral resection of large uveal melanoma.MethodsRetrospective interventional case series, including 106 consecutive patients. Local tumour control, enucleation and metastasis development...

High-powered microwave ablation of larger hepatocellular carcinoma: evaluation of recurrence rate and factors related to recurrence

To evaluate the safety and efficacy of high-powered (80-100W) percutaneous microwave ablation (MWA) at a frequency of 2450±10MHz for treating larger hepatocellular carcinoma (HCC) and to predict the risk factors of local recurrence after high-powered MWA. The study was approved by the Institutional Review Board, and informed consent was waived because of the retrospective study design. Forty-five patients with a total of 60 lesions received high-power (80-100W) MWA at a frequency of 2450±10MHz through a percutaneous approach that was guided by ultrasound. Of the 60 lesions with a maximum tumour measuring 3-8cm, 46 lesions were 3-5cm and 14 were 5-8cm. The complete ablation rates, local recurrence rates, complications, and short-term survival were analysed. Ten possible risk factors for local recurrence were analysed. The complete ablation rates were 82.61% for the first ablation and 100% for the second ablation for 3-5cm lesions. The complete ablation rates were 64.29% (82.61% versus 64.29%, p=0.037) for the first ablation and 85.71% (100% versus 85.71%, p=0.055) for the second ablation for 5-8cm lesions. Local recurrence was observed in 11 out of the 45 (24.44%) successfully treated patients. The 1-year and 2-year survival rates were 95.56% (43/45) and 86.67% (39/45), respectively. No procedure-related mortality was observed and no major bleeding, liver rupture, or liver abscesses occurred. Univariate analysis showed that a positive correlation existed between the number of lesions (p=0.022), proximity to the risk area (p=0.001), pre-ablation alpha-fetoprotein (AFP) levels (p=0.025), hepatitis B virus (HBV)-DNA replication (p=0.027) and local recurrence. Multivariate analysis identified HBV-DNA (p=0.031) and proximity to the risk area (p=0.039) as the independent prognosis factors causing postoperative HCC local recurrence. High-powered MWA of larger hepatocellular carcinomas appears to be a safe and effective treatment. HBV-DNA and proximity to the risk area appear to be independent predictors of local tumour recurrence.

Early postoperative magnet resonance tomography after resection of cerebral metastases.

In contrast to malignant gliomas, the impact of an early postoperative MRI after surgery of cerebral metastasis is still unclear. The present study analyses early MRI-based postoperative resection controls and incidence of in-brain progression in 116 patients suffering from 130 cerebral metastases. The extent of surgical resection was verified by an early postoperative contrast-enhanced 1.5-T MRI within 72 h after surgery of cerebral metastases and correlated with in-brain progression, leptomeningeal carcinomatosis, and progression-free survival. MRI confirmed complete resection was seen in 80 out of 130 metastases (61.5 %). In 24 metastases (18.5 %), no final decision on degree of resection could be made. Residual tumor was seen in 26 cases (20 %). Local in-brain progression was observed in 40 of 130 (30.8 %) cases. The incidence of in-brain progression significantly correlated with dural contact of the metastasis (p < 0.05) and residual tumor on early postoperative MRI (p < 0.0001). The odds ratio for local recurrence with residual tumor is 8.2-fold compared to no residual tumor. Residual tumor after metastasis extirpation was shown in nearly 20 % of patients by an early postoperative MRI and significantly correlated with local in-brain progression. Furthermore, dural contact of cerebral metastases was identified as a risk factor for local recurrence. Further studies are mandatory to clearly identify the incidence of incomplete resections of cerebral metastases and their oncologic impact. An early postoperative MRI after resection of cerebral metastases is recommended as residual tumor promotes local recurrence.

Local Recurrence After Primary Proton Beam Therapy in Uveal Melanoma: Risk Factors, Retreatment Approaches, and Outcome

To evaluate the risk factors, recurrence rates, retreatments, and long-term patient outcomes following proton beam therapy for uveal melanoma. Retrospective interventional case series. All patients treated with primary proton beam therapy for uveal melanoma at the oncology service at Charité-Berlin and Helmholtz-Zentrum-Berlin between May 1998 and December 2008 were reviewed for local recurrence. Of 982 patients, 982 eyes matched the inclusion criteria. The data were obtained from electronic health records, operative reports, discharge letters, and radiation planning. Comparisons of fundus photographs and ultrasound measurements were performed to assess the growth pattern of the tumor and to determine the success of retreatment, in the case that a globe-retaining therapy was undertaken. Of 982 patients, 35 patients (3.6%) developed local recurrence. The median follow-up was 60.7 months (6.0-170.4 months). Local control rate was 96.4% and the overall eye retention rate was 95.0% in this cohort. Local recurrence was correlated with a higher risk for metastasis and reduced survival. Largest tumor diameter was identified as the sole statistically significant risk factor for local recurrence (P = .00001). All globe-retaining retreatment approaches for local recurrence, including proton beam therapy, brachytherapy, and transpupillary thermotherapy used for recurrences at the tumor margins, showed good local tumor control and similar metastasis-free survivals. This study showed that each globe-retaining retreatment approach can result in satisfying local tumor control. In case of early detection of local recurrence, preservation of the globe can be warranted. Therefore, regularly performed follow-ups should be ensured.