bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy compared with hepatic resection for metastatic colorectal cancer.
Authors: Blackham Aaron Udell , Russell Greg B. , Stewart John H. , Votanopoulos Konstantinos Ioannis , Levine Edward Allen , Shen Perry
Published: February 2017

630

Background: Surgical resection of peritoneal metastases (PM) from colorectal cancer has been reported to yield outcomes similar to liver resection for hepatic metastases (HM). However recent data suggests PM may have a worse prognosis than other metastatic sites.

Methods: A review of metastatic colorectal cancer patients obtained from prospective databases (1992-2010) comparing liver resection for HM to cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for PM.

Results: 181 patients underwent hepatic resection and 182 patients underwent CS/HIPEC with a median follow-up of 55 and 106 months respectively. A margin-negative resection was obtained in 168 (93%) hepatic resections, while 89 patients (49%) with PM had complete cytorection of all gross disease (R0/R1). A comparison of these two groups demonstrated significant differences in age, pre-operative chemotherapy and performance status. Disease-free median survival was 15.2 months after hepatic resection and 9.9 months after CS/ HIPEC (p=0.02). The 5-year overall survival (OS) for HM patients was 33% with a median OS of 45.0 months; while 5-year OS was 23% and median OS was 32.3 months for PM patients (p=0.02). In a proportional hazards regression model, performance status and pre-operative chemotherapy had no significant effect on survival, while increased age (p=0.02) and PM (p=0.03) were associated with decreased OS. Postoperative morbidity was 38% versus 51% (p=0.04) and mortality was 3.0% versus 2.3% (p=0.73) in the HM and PM groups, respectively.

Conclusions: Disease-free survival and OS are worse for patients who received complete cytoreduction and CS/HIPEC for PM compared to margin-negative liver resection for HM suggesting a more aggressive tumor biology in PM.
The influence of seminal events on the transition from adjuvant to neoadjuvant chemoradiation in the treatment of locally advanced rectal adenocarcinoma (LARC).
Authors: Warner Jeremy , Miksad Rebecca A. , Nagle Deborah , Najarian Robert , Goldstein Michael
Published: February 2017

631

Background: Factors leading to uptake of new oncology treatment innovations are poorly understood. In particular, the degree to which seminal events, such as report of pivotal phase III trials, influence practice is unclear. For example, preoperative (pre-op) 5-fluorouracil + radiation (5-FU + RT) is the current standard of care for definitive treatment of LARC. However, postoperative (post-op) 5-FU + RT was standard before the seminal German Rectal Cancer Study Group (GRCSG) results were published. We investigated the impact of seminal events on the change in practice pattern from pre- to post-op 5-FU + RT at our institution.

Methods: Patients with LARC (T2N+; any T3; any T4) treated at our institution between 1994-2010 were identified from the cancer registry. The date of diagnosis was compared to the dates of three seminal events: A) JAMA meta-analysis publication; B) publication of GRCSG results; C) founding of a multidisciplinary clinic at our institution. Pearson Chi square was used for univariate analysis.

Results: 334 patients were evaluable. RT +/- 5-FU was delivered pre-op for 207 patients, post-op for 127 patients. The unadjusted odds ratio (OR) for receiving pre-op treatment after vs. before each seminal event was similar: (A) 4.16; (B) 4.08; (C) 3.91. When patients diagnosed prior to (A) or after (C) were excluded, (B) appeared to have a smaller effect, OR 2.07 (p = .053) (Table).

Conclusions: All seminal events had similar associated OR, indicating that the process of uptake of the innovation of pre-op 5-FU + RT was gradual. The seminal GRCSG publication, when temporally isolated, had only modest effect. This suggests that report of seminal results is necessary but not sufficient for uptake of a new therapy innovation in LARC at our institution. Whether this pattern of uptake is generalizable is worthy of further investigation.

[Table: see text]
Panitumumab (Pmab) versus cetuximab (Cmab)/irinotecan (Iri) therapy among patients with KRAS wild-type (wt) metastatic colorectal cancer (MCRC).
Authors: Kennecke Hagen F. , Chen Leo , Blanke C. D. , Cheung Winson Y. , Schaff Kimberly , Speers Caroline
Published: February 2017

640

Background: In British Columbia, use of anti-EGFR therapy for KRAS wt MCRC is limited to patients (pts) previously treated with both irinotecan and oxaliplatin. Physicians may choose either Pmab monotherapy or Cmab/Iri combination therapy. We sought to compare the characteristics and outcomes of all pts treated with Pmab/Cmab referred to 5 provincial cancer centers since July, 2009.

Methods: Eligible patients received at least one dose of either Pmab (6mg/kg q2w) or Cetuximab (500mg/m2 q2w) plus Iri (180mg/m2 q2w). Baseline characteristics and systemic therapy were prospectively collected, while ECOG and metastatectomy status were retrospectively collected. Kaplan-Meier survival analysis was conducted from the first day of Pmab/Cmab.

Results: Among 178 eligible pts, Pmab was chosen 3 times more often than Cmab/Iri (see table). Pts treated with Cmab/Iri were significantly younger and had better performance status than those treated with Pmab. There were no statistically significant differences in other prognostic variables, and a similar proportion received chemotherapy after Pmab vs. Cmab/Iri. Overall survival was slightly longer among patients receiving Cmab/Iri (8.3 mo), vs. Pmab (7.7 mo) (p=.03).

Conclusions: Pmab was chosen more often than Cmab/Iri for similarly eligible patients. Cmab/Iri pts were younger, were more likely to have ECOG performance status 0/1 and achieved a modestly longer overall survival. Either regimen appears to be suitable for previously treated pts with KRAS wt MCRC.

[Table: see text]
Modified FOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab beyond first progression in advanced colorectal cancer: CCOG-0801 study.
Authors: Ishigure Kiyoshi , Nakayama Goro , Uehara Keisuke , Yokoyama Hiroyuki , Ishiyama Akiharu , Eguchi Takehiko , Tsuboi Kenji , Ando Yuichi , Kodera Yasuhiro
Published: February 2017

641

Background: Bevacizumab provides survival benefit as the first-line and second-line therapies in metastatic colorectal cancer (mCRC). A large observational study suggested use of bevacizumab beyond first progression (BBP) improved survival. This prompted us to conduct a multicenter phase II study of mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizimab in mCRC to further explore the strategy of BBP in Japanese patients.

Methods: Previously untreated patients with assessable disease were treated with mFOLFOX6 plus bevacizumab until tumor progression, followed by FOLFIRI plus bevacizumab. The primary endpoint of the study was the second progression-free survival (2nd PFS), defined as duration from enrollment until progression after the second-line therapy. If the patient failed to receive the second-line treatment due to medical reasons or refusal, the PFS during the first-line therapy was used for analysis. Secondary endpoints were PFS, overall survival (OS), response rate (RR), disease control rate (DCR) and safety.

Results: In the first-line therapy, 47 patients treated with mFOLFOX6 plus bevacizumab achieved RR of 61.7%, DCR of 89.4% and median PFS of 11.7 months. Thirty patients went on to receive the second-line therapy with FOLFIRI plus bevacizumab and achieved RR of 27.6%, DCR of 62.1%, and median PFS of 6.0 months. Median 2nd PFS was 16.2 months. Median survival time did not reach the median follow-up time of 27.4 months. Severe adverse events associated with bevacizumab during the first-line therapy were a venous thromboembolic event in one case (2%), a grade 2 bleeding event in one case (2%) and GI perforation in one case (2%). However, no critical events associated with bevacizumab were reported during the second-line therapy.

Conclusions: The planned continuation of bevacizumab during the second line treatment is feasible in Japanese mCRC patients. A prospective randomized control study to confirm the efficacy has to be conducted in the future.
A phase I/II study of biweekly XELIRI plus bevacizumab for patients with metastatic colorectal cancer as second-line chemotherapy (BIXER study): Reports of phase I part and interim analysis of phase II part.
Authors: Suenaga Mitsukuni , Matsusaka Satoshi , Shinozaki Eiji , Mizunuma Nobuyuki , Hatake Kiyohiko , Yamaguchi Toshiharu
Published: February 2017

643

Background: Capecitabine is an oral fluoropyrimidine prodrug, which is converted to fluorouracil (5-FU) predominantly in the tumor cells. In Japan, capecitabine is mainly used in combination with oxaliplatin (XELOX) in treatment for metastatic colorectal cancer (mCRC) since its approval in 2009. The results of capecitabine plus Irinotecan (CPT) (XELIRI) with or without bevacizumab (BV) in EU or US patients were previously reported, but not in Japanese. Thus, we conducted this study to assess the safety and efficacy of XELIRI plus BV in Japanese patients with mCRC.

Methods: Patients with prior chemotherapy including oxaliplatin and BV for mCRC, wild or hetero type of UGT1A1 *6*28 were eligible for this study. This was a phase I study composed of two steps, and dose limiting toxicity (DLT) was assessed during the first treatment cycle. Treatment comprised capecitabine 1,000 mg/m2 twice daily from the evening of day 1 to the morning of day 8, intravenous CPT 180 mg/m2 on day 1, and BV 5mg/kg on day 1 every two weeks. To evaluate the initial safety, 3-6 patients received XELIRI+BV (CPT 150mg/m2) in step 1, and 6 patients received XELIRI+BV (CPT 180mg/m2) in step 2. If DLT occurred in 1 patient in step1, 3 patients would be newly added to step 1, and if in none of 3 or 1-2 of 6 patients, the step 2 would be started. If DLT occurred in less than or equal to 2 of 6 patients in step 2, phase II study would be proceeded, and if In more than 2 of 6 patients, phase II would be conducted at the recommended dose of step 1.

Results: In step 1 and 2 of phase I, initial safety of 9 patients was confirmed without occurrence of DLT. Adverse events observed in step 1 and 2 were: neutropenia in 2 and 1; anorexia in 1 and 1; diarrhea in 1 and 1; stomatitis in 1 and 1; alanine or aspartate aminotransferase increased in 1 and 3, respectively. There was no grade 3 or greater adverse events.

Conclusions: In mCRC patients with wild or hetero of UGT1A1*6*28 genotype, safety of biweekly XELIRI+BV was confirmed and recommended dose of CPT-11 was determined as 180mg/m2. Interim analysis of safety of phase II part will be reported at the meeting.
Effectiveness of gemcitabine and capecitabine in advanced colorectal cancer patients: A retrospective analysis.
Authors: Salgado Mercedes , Reboredo Margarita , Medina Ana , Quintero Guillermo , Pellon Maria Luz , Romero Reinoso Carlos , Jorge Mónica , Fernandez-Montes Ana ,   Asociacion Grupo Gallego de Investigacion en Tumores Digestivos (GITuD)
Published: February 2017

649

Background: In ASCO2004, Y. Fernandez et al. showed their experience in gemcitabine/capecitabine use in patients with metastatic advanced colorectal cancer (ACRC), with previous progression or contraindicated standar treatment, with encouraging results. This study was design to evaluate the efficacy and safety of this combination in these patients, in our area.

Methods: This is an observational, multicentric and retrospective study performed in metastatic colorectal cancer patients refractory to treatment. The study treatment was to evaluate the gemcitabine/capecitabine (gemcitabine 1000 mg/m2, day 1+ capecitabine 1250 mg/m2/12hours, days 1-7, every 15 days) until progression or unacceptable toxicity. The principal endpoint was the best overall response rate achieved during the study period. Secondary endpoints were Progresión Free Survival (PFS), Overall Survival (OS) and safety profile.

Results: Of 45 patients recruited a total of 39 patients were evaluated. Median age was 66(37-78) and 69.2 were male. 86.8% of the patients were ECOG PS 1. Mean time from diagnostic was 2.7±2.4 years. Primary tumor was: colon 73.7%, rectum 23.7% and both 2.6%. Adjuvant therapy was received in 34.3% of the patients. Metastatic locations were: liver 82.1%, lung 64.1% and lymph nodes 25.6%. Previous treatment lines received: two 48.7%, three 23.1%, four 17.9%, five 7.7% and six 2.6%. The mean of cycles were 6.4±6 and mean time of treatment was 3.3±2.8 months. Best response during treatment period was partial response 2.9%, stable disease 17.6% and progression 79.4%. OS was 7.32 months and median PFS was 3.02 months. Most frequent toxicities grade 3 experienced: Palmar plantar erythrodysesthesia 5.1%, neutropenia 5.1%, asthenia 2.6%, dyspnea 2.6% and hiperbilirrubinemia 2.6%. No grade 4 toxicities were reported.

Conclusions: Despite of the adequate safety profile of the gemcitabine/capecitabine combination, our study does not confirm the efficacy figures reported by others authors. New agents or combinations should be investigated in the treatment of this patient subgroup.
Prescribing patterns for bevacizumab in first-line metastatic colorectal cancer: Exploring the introduction of a new drug into routine clinical practice.
Authors: Field Kathryn Maree , Desai Jayesh , Tie Jeanne , Kosmider Suzanne , Bae Susie , McKendrick Joseph James , Harold Michael , Gibbs Peter
Published: February 2017

665

Background: Clinical trials support the addition of bevacizumab (Bev) to first line chemotherapy for metastatic colorectal cancer (mCRC). However, given that there are alternate biological agents that can be used with chemotherapy; and rare but potentially serious toxicities with Bev, there has been variable use of the drug in routine care. The purpose of this study was to prospectively explore 1st line use of Bev in routine clinical care.

Methods: A multi-site data collection was initiated in July 2009 when Bev became publicly available in Australia. A particular focus was capturing information regarding clinician decision-making that is not routinely recorded or is often poorly documented. Comprehensive comorbidity data was collected, along with specific factors, both patient (pt) and disease-related, that may impact on treatment decisions. Major adverse events that may be related to Bev were also recorded.

Results: For the 2-year period from July 2009-June 2011, a database search identified 278 pts diagnosed with mCRC at five participating hospitals. 240 pts (86%) had received 1st line chemotherapy. 102 (43%) also received Bev, the majority in combination with oxaliplatin based chemotherapy (n = 81, 79%). Bev use increased significantly from 40.4% (34/84) of all pts receiving chemotherapy in July-December 2009, to 65.8% (25/38) in January-June 2011 (p=0.0114). Overall the most frequent reasons for clinicians advising against the use of Bev were a bleeding or asymptomatic primary in situ (n=28, 23%), known hypertension (n=14, 11%), clinical trial participation (n=14, 11%), poor performance status (n=9, 7%), and perceived risk of arterial ischemic event (n=8, 6.5%). There have been four episodes of gastro-intestinal perforation, 3 in pts receiving Bev (2.9% of Bev treated patients).

Conclusions: Bev use in first line mCRC has significantly increased over time, presumably as further positive safety data emerges regarding safety in older and frailer pts, and clinician prescribing experience increases. The major grounds for not using Bev in the 1st line mCRC setting were specific clinical contexts where the risk of adverse events may be increased.
Development of a comprehensive set of colorectal cancer care quality metrics.
Authors: McCahill Laurence E. , Kokko Jamie , Werkemma Chris , Ebrom Pierson , Khandavalli Sarat
Published: February 2017

670

Background: Institute of Medicine report calls for improved quality of cancer care. Numerous entities have sought measures of health care quality, but there is limited consensus regarding metrics for quality of colorectal cancer (CRC) care. Current measures are very limited; there exist no comprehensive metrics for quality of CRC care across the continuum of care. We sought to identify robust quality metrics, including measures related to pathology, coordination of cancer care, surgery, radiation, chemotherapy and surveillance, in order to identify gaps in quality of CRC care.

Methods: National guidelines (NCCN and ASCO), National Quality Forum, and select peer reviewed publications were reviewed to develop evidence based metrics to assess quality of CRC care from diagnosis to post treatment surveillance and survivorship. A core group of health care providers, including a surgical oncologist, a pathologist and a Cancer nurse practitioner developed the metrics based on literature review. Measures were reviewed by key physician stakeholders including Radiation Oncology, Medical Oncology, General surgery, and Gastroenterology to obtain support for the quality initiative at our institution.

Results: Twenty-three quality metrics were developed including 6 metrics related to access and process, 6 related to pathology, 7 related to multidisciplinary care and 4 measures related to surveillance and survivorship. Novel metrics included documentation of a three generational cancer family history, documentation of preoperative CT imaging of chest/abdomen/pelvis, MSI and KRAS testing in specific populations, appropriate pre-operative radiation oncologist evaluation for rectal cancer, multidisciplinary team planning prior to treatment initiation for rectal cancer and patients with newly identified liver metastases, appropriate referral for genetic counseling and surveillance annual CT scans for 3 years post treatment.

Conclusions: These novel and comprehensive metrics allow for detailed review of the quality of CRC care received by patients at our institution. Individual patient data are currently being abstracted to assess the utility and logistics of implementing these quality metrics at a community cancer center.
Retrospective analysis of pathologic response in colorectal cancer liver-only metastases following treatment with bevacizumab.
Authors: Vera Ruth , Figueras Joan , Gomez Dorronsoro Maria Luisa , Lopez-Ben S. , Viúdez Antonio , Queralt Bernardo , Hernandez Irene , Scalzone R. , Zazpe Cruz , Ortiz R.
Published: February 2017

674

Background: Recent reports have shown that pathological response predicts for better outcome (overall survival) following preoperative chemotherapy and surgical resection of colorectal cancer (CRC) liver-only metastases. The aim of this retrospective analysis was to evaluate the effect of adding bevacizumab to standard chemotherapy on pathological response in patients with CRC liver only metastases.

Methods: Patients with stage IV CRC with liver metastases who received neoadjuvant chemotherapy (oxaliplatin-or irinotecan-based) at two Spanish centres were analysed retrospectively. Pathological response was evaluated as follows: complete pathological response (cPR), PR1 (25% of residual tumour), PR2 (25–50% of residual tumour), PR3 (>50% of residual tumour). cPR or PR1 was considered to be a good response, and PR2 or PR3 a poor response.

Results: A total of 81 patients were evaluated. Of these, 43 received chemotherapy alone and 38 received chemotherapy plus bevacizumab. Baseline characteristics were as follows: median age 61.0 years (range 43.0–80.0 years); male/female (67%/33%); tumour location – colon (69%) / rectum (31%); hepatic metastases – synchronous (74%) / metachronous (26%); In terms of pathological response, 58% of patients receiving bevacizumab had a good response (cPR + PR1) compared with 28% of those receiving chemotherapy alone. At the end of the analysis, 68% of patients were still alive.

Conclusions: Adding bevacizumab to oxaliplatin-based chemotherapy in the neoadjuvant setting improves the pathological response of liver metastases in patients with stage IV CRC. These findings indicate that pathological response might be a good indicator of outcome for patients receiving bevacizumab in the neoadjuvant setting.
Comparison between the three oxaliplatin-based regimens with bevacizumab in patients with metastatic colorectal cancer.
Authors: Ohhara Yoshihito , Suenaga Mitsukuni , Matsusaka Satoshi , Shinozaki Eiji , Mizunuma Nobuyuki , Yamaguchi Toshiharu , Hatake Kiyohiko
Published: February 2017

687

Background: XELOX (capecitabine/L-OHP) therapy that includes orally administered ﬂuoropyrimidine instead of infusional fluorouracil (5-FU) was approved for metastatic colorectal cancer (mCRC) in Sep 2009 in Japan. A pivotal trial (NO16966 study) demonstrated the non-inferiority of XELOX to FOLFOX (5-FU/L-OHP/LV) and the superiority of those L-OHP-based regimens plus bevacizumab (BV) to those without in the first-line treatment of mCRC. We evaluated the safety and efficacy of XELO+BV compared with FOLFOX4 or mFOLFOX6 plus BV in the first-line treatment for mCRC patients at a single institute.

Methods: Between Jun 2007 and Nov 2008, 85 patients received FOLFOX4+BV (FF4 arm), between Dec 2008 and Sep 2009, 40 patients received mFOLFOX6+BV (FF6 arm), and between Oct 2009 and Sep 2010, 60 patients received XELOX+BV (XELOX arm). The best overall responses were evaluated using RECIST 1.0 during chemotherapeutic treatment, and adverse events were graded according to CTCAE ver.3.0. Progression-free survival (PFS) was estimated by Kaplan-Meier methods.

Results: Characteristics of patients of FF4 arm, FF6 arm, and XELOX arm were below: median age, 60 yr vs. 62 yr vs. 60.5 yr; gender (male), 48.2 % vs. 62.5 % vs. 58.3%. The overall response rates (CR+PR) were 61.1 %, 72.5 %, and 75 % (95% CI; 50.6-71.8%, 58.0-87.0%, and 63.7-86.3%). Median PFS were 17.0 months, 15.5 months, and 14.4 months, respectively (cut-off: Aug 31, 2011). There were no statistical significances not only between FF4 arm and FF6 arm (log-rank; p=0.641), but also between XELOX arm and FF4+FF6 (FOLFOX) arm (log-rank; p=0.138). FOLFOX arm was associated with higher incidence of grade 3/4 neutropenia than XELOX arm. Grade3 diarrhea and hand-foot syndrome (HFS) were more frequent in XELOX arm.

Conclusions: This study suggests that XELOX arm was equal to FOLFOX arm, regardless of regimen, in tumor response and PFS. Further follow-up is necessary to confirm the benefit on survival.
Cardiotoxicity of 5-fluorouracil in patients with gastrointestinal cancer.
Authors: Lopez Lourdes , Montenegro Paola Catherine
Published: February 2017

689

Background: 5-fluorouracil (5-FU) is a agent of chemotherapy that has been associated with cardiotoxicity infrequently. The reports shown incidence of clinically apparent 5-FU cardiotoxicity in 1.6% for patients receiving 5-FU alone or in combination with another agents.

Methods: We investigated the clinical characteristics of 5-FU cardiotoxicity in patients with gastrointestinal cancer treated in instituto nacional de enfermedades neoplasicas (INEN) Lima - Peru between October 2009 and October 2010.

Results: Between October 2009 and October 2010, were evaluated 240 cases with gastrointestinal cancer treated with 5-FU alone or plus combinations with another chemotherapy agent, 8 cases (3.3%) had cardiotoxicity. 37.5 % had history of cardiovascular disease, 3 patients had a history of hypertension and 1 patient diabetes mellitus plus hypertension. 50% (4 patients ) had normal EKG prior to treatment, 25% (2 patients) had no EKG, In 12.5% (1patient) had sinus tachycardia and another patient had ventricular extrasystoles were detected. After chemotherapy infusion 75% (6) had changes in the EKG. In 8 patients was observed as the main symptom chest pain with radiation to left arm or upper back, without elevated cardiac enzymes. 87.5% (7 patients ) had symptoms after 6 pm. And the duration of symptoms was 48 hours in 62.5% (5 patients), 12.5% (1patient ) in 24 hours and 6 hours in 12.5% (1 patient). One patient died of acute heart failure and had history of hypertension and diabetes mellitus and received the combination cisplatin - 5-FU.

Conclusions: The eight cases reports confirm the potential cardiotoxicity of 5-FU and argues the need for cardiovascular assessment by a specialist before the start of treatment in addition to cardiac monitoring in patients during treatment, especially in patients with risk factors especially in the first cycle, women and at night. The mechanism of 5-FU cardiotoxicity is not fully elucidated. Coronary spasm is the most accepted hypothesis.
Laparoscopic gastrectomy for gastric adenocarcinoma: A single institution’s experience and oncologic outcomes of 65 consecutive patients.
Authors: Arrington Amanda Kathleen , Ho Joyce , Kim Joseph , Trisal Vijay , Ellenhorn Joshua D. I.
Published: February 2017

79

Background: The application of laparoscopy in the surgical treatment of gastric cancer has become more commonly utilized in recent years. Most of the published series are from Asia and few report on survival. Our objective was to elucidate the safety, efficacy, and oncologic outcomes of laparoscopic gastrectomy in patients with gastric adenocarcinoma.

Methods: The medical records of all patients who underwent laparoscopic gastrectomy at City of Hope National Medical Center between 6/2005 and 8/2011 were retrospectively reviewed. Relevant data analyzed included patient demographics, operative parameters, complications, recurrence, and survival.

Results: A total of 65 consecutive patients were identified. Of all laparoscopic procedures, 5 were proximal, 41 were distal, and 19 were total gastrectomies. Median age was 67 years (35-96). Median operative time was 370 min (228-583). Median EBL was 200 ml (10-900). Twenty-eight of the 65 laparoscopic gastrectomy cases employed robotic assistance in lymph node dissection. The median number of lymph nodes retrieved was 26. Forty-seven cases included D2 lymph node dissections, 16 cases were D1 dissections, and 2 cases involved D0 dissections. All intended D2 dissections had greater than 15 nodes retrieved. Median hospital stay was 7 days (3-39). Morbidity and mortality rates were 33% and 3%, respectively. Histological staging revealed most patients with Stage I or II disease. Median follow-up was 15 months (0.5 to 58). Cancer has recurred in 4 patients (6%). The 3-year overall survival for stage I disease (N=38) is 92%, stage II disease (N=17) is 71%, and for stage III (N=7) is 51%.

Conclusions: The long-term oncologic outcomes and overall survival are comparable to that of open technique seen in other series. Our large institutional series shows that laparoscopic gastrectomy for gastric adenocarcinoma is feasible and safe and can be performed in patients with gastric cancer with excellent surgical and oncologic outcomes.
Definitive (chemo)radiotherapy in patients with esophageal cancer: A population-based study in northeast Netherlands.
Authors: Smit Justin Kendrick , Muijs Christina T. , Timmer Paul R. , Paardekooper Gabriel , Muller Karin , Woutersen Dankert , Mul Veronique E. , Beukema Jannet , Hospers Geke A. , Langendijk Johannes A. , Plukker John Theodorus
Published: February 2017

83

Background: Definitive (chemo)radiation as primary treatment modality is offered to esophageal cancer (EC) patients, as an alternative for patients considered medically unfit for surgery or having irresectable tumors. We evaluated the results in our cohort to improve selection of patients for intensified non-surgical strategies and to identify which clinical factors have a prognostic impact on the overall (OS) and disease free survival (DFS).

Methods: EC patients treated with definitive radiotherapy (RT) or chemoradiotherapy (CRT) from 4 radiotherapy referral centers between 1996 and 2008 were used. Only patients with squamouscellcarcinoma (SCC) or adenocarcinoma (AC) were included in the analyses.

Results: In total 278 patients were identified of whom 106 (38.1%) were treated with CRT (platinum based, median 50.4 (46.8 – 70)Gy) and 172 (61.9%) with RT alone (median 60 (40-70)Gy). T- stage was cT1=5.6%;cT2=15.3%;cT3=60.9% and cT4=18.2%. Nodal stage consisted of cN0=35%;cN1=65%, including cM1a=5.8%. The male/female ratio was 78.3% to 21.7%. AC occurred in 57.6% and 42.4% had a SCC. The median age was 69 years. Median OS time was 11 (1-166) months with an OS of 45%, 22% and 6% and a DFS of 32%, 18% and 6% at 1, 2 and 5 years, respectively. There was no significant difference between the CRT and RT group in OS (p=0.09) and DFS (p=0.17). The DFS after 2 and 5 year was 25% and 12% for SCC patients versus 11% and 0% for AC patients (p=0.007). The OS at 2 and 5 year was 28% and 11% for SCC versus 14% and 0% for AC patients (p=0.020). Initial recurrence was seen locoregionally in 66.7% and distant metastases occurred in 33.3%. Common sites for distant recurrence were the liver with 52.4%, 17.5% bones and 15.5% lungs. Patients with SCC had a better response to (chemo)radiotherapy considering the OS (p=0.02, HR=0.7) and DFS (p=0.01, HR=0.69) in a multivariate analysis.

Conclusions: Patients with a SCC esophageal tumor have better long-term results then AC patients after definitive (chemo)radiation. In this patient group SCC seems to be a strong prognostic factor for both OS and DFS. Furthermore the difference between RT and CRT is still small.
Effect of post-operative intra-abdominal infectious complications on overall and relapse-free survival following curative gastrectomy in patients with gastric cancer.
Authors: Tokunaga Masanori , Tanizawa Yutaka , Bando Etsuro , Kawamura Taiichi , Terashima Masanori
Published: February 2017

86

Background: The number of reports investigating the impact of postoperative complications on long-term outcome following curative gastrectomy is limited and still remains unclear. The aim of this study is to clarify the effect of postoperative intra-abdominal infectious complications on overall survival (OS) and relapse-free survival (RFS) following curative gastrectomy.

Methods: Three hundred and sixty-seven patients pts who underwent curative gastrectomy for gastric cancer between June 2003 and December 2004 at Shizuoka Cancer Center were included. Clinicopathological features and effects of postoperative intra-abdominal infectious complications on OS and RFS were investigated. In this study, postoperative intra-abdominal infectious complications were defined as Clavien-Dindo grade II or more severe pancreas fistula, anastomotic leak, or intra-abdominal abscess.

Results: Median age was 63 years, male-female ratio was 2:1. Pathological stage was Stage I; 225 patients, stage II; 72 patients, stage III; 64 patients, and stage IV; 6 patients. Median observation periods of survivors were 71 months. Of 367 patients, 32 patients (8.7%) had intra-abdominal infectious complications. Overall 5-year survival rate was significantly better in patients without complications than in those with complications (86.1 vs 67.9%, P<0.001). The same trend was observed even after stratification by pathological stage (Stage II; 76.9 vs 66.7%, P=0.254, Stage III; 62.1 vs 40.9%, P=0.218) although each difference was not statistically significant. Relapse free 5-year survival rate was significantly better in patient without complications (85.0 vs 64.9%, P=0.002), and the same trend was also observed after stratification by pathological stage.

Conclusions: Postoperative intra-abdominal infectious complications adversely affect overall and relapse free survival of patients following curative gastrectomy. Reduced incidence of infectious complications may be beneficial to improve long-term outcome of patients with gastric cancer.
Patterns of failure following trimodality therapy for locally advanced esophageal cancer (EC).
Authors: Dorth Jennifer Anne , Willett Christopher , Czito Brian G.
Published: February 2017

88

Background: Patterns of local-regional failure (LRF) after neoadjuvant chemoradiotherapy (CRT) and surgery for locally-advanced EC are poorly defined.

Methods: This study reviewed pts treated with CRT followed by surgery for M0 esophageal cancer from 1995-2009. Staging and regional nodes (supraclavicular (SCV) through celiac) were defined based on AJCC 7th edition. Patterns of first failure were analyzed. LRF included: 1) initially involved nodal failure (INF), 2) initially uninvolved (subclinical) nodal failure (SNF), and/or 3) anastomotic. Abdominal para-aortic failure (PAF) at or below the superior mesenteric artery was scored separately. Isolated SNF or PAF was defined as no other local or distant failure. Actuarial local-regional control (LRC), event-free survival (EFS), and overall survival (OS) were estimated by the Kaplan-Meier method.

Results: 156 patients were identified with a median age of 60 years. Primary location was upper in 1%, middle 17%, lower 32% and gastroesophageal junction (GEJ) 50% (Adeno: 79%; SCC: 21%). Staging included EUS (73%), CT (46%), and/or PET/CT (54%). 40% had stage II and 60% stage III disease. Concurrent CRT was primarily cisplatin/taxane and/or 5-FU-based. Primary RT fields (median dose: 45Gy) encompassed the tumor with an approximate 5 cm proximal and distal margin and included standard regional nodes. Boost fields (median total dose: 50.4Gy) encompassed gross disease with a 2 cm margin. Surgical technique was transhiatial (28%), Ivor-Lewis (47%), or tri-incisional (25%) with a median of 8 nodes dissected. Median f/u was 1.3 years. 2-yr LRC, EFS, and OS were 83%, 36%, and 49%. 2-yr SNF was 15% (n=14); anastomotic failure was 7% (n=7). SNFs were SCV (n=5), mediastinal (n=12), and/or celiac (n=3). 95% of SNFs were outside or near the margin of the primary RT fields. 2-yr isolated SNF was 3% (n=3), PAF was 11% (n=9), and isolated PAF 6% (n=5).

Conclusions: SNF is the most common type of LRF after tri-modality therapy for locally-advanced EC. A limited subset of patients experience isolated SNF or PAF as first disease recurrence. The potential benefit of targeting additional SN or PA regions with RT is small and likely eclipsed by high rates of distant failure.
Chemoradiotherapy plus surgery versus surgery alone for resectable esophageal cancer: A systematic review of randomized control trials.
Authors: Njei Basile M. , Appiah Juliet , Ditah Ivo C. , Birk John W.
Published: February 2017

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Background: Several trials have demonstrated better survival when surgery is combined with neoadjuvant chemotherapy and concurrent radiotherapy (CRT) in the treatment of esophageal cancer (EC). However, it is unclear whether survival benefits are counterbalanced by a poor quality of life due to the adverse effects of the combination therapy. The aim of this study was to compare the efficacy and safety of CRT plus surgery versus surgery alone.

Methods: Two authors independently conducted a comprehensive search of the Cochrane library PUBMED, MEDLINE, and published proceedings from major oncologic cancer meetings from January 1980 to July 2011. The titles and abstracts of all potentially relevant studies were screened for eligibility. In addition to overall outcome measures, subgroup analysis by histology of EC (squamous cell cancer [SCC] and adenocarcinoma [AC]), was also performed. Analysis was done using the fixed effect model. The Begg’s and Egger’s tests with visual inspection of the funnel plot were used to assess for population bias.

Results: Fifteen studies involving 1,957 patients were included in the analysis. There was an overall statistically significant increase in the 5-year survival for the CRT plus surgery group versus the surgery only group (RR 1.47, 95% CI 1.24-1.76). By histological type, only patients with SCC showed prolonged survival: RR 1.53, 95% CI 1.26-1.85. We equally found an overall significant increase in grade 3 and 4 adverse events in the CRT plus surgery group compared to the group with surgery alone (RR 1.73, 95% CI 1.15-2.60). Again, a significant increase in serious adverse events was observed only in the sub-group of patients with SCC (RR 1.81, 95% CI 1.14-2.86). There was no evidence of heterogeneity or publication bias in these analyses.

Conclusions: Overall, CRT plus surgery can improve long-term survival in EC patients. The results seem to be limited only to patients with SCC and not AC. However, the prolonged survival comes at the cost of poorer quality of life due to a higher incidence of adverse events. For the moment we recommend that the decision on what treatment strategy to use be based on informed patient preference.
Prostate cancer–specific mortality and competing causes of mortality among elderly men after local therapy for prostate cancer.
Authors: Mir Maria Carmen , Klink Joseph C. , Isariyawongse Brandon , Kibel Adam Stuart , Klein Eric A. , Stephenson Andrew J.
Published: February 2017

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Background: The benefit of definitive local therapy among elderly patients (> 65 years) with localized prostate cancer (PC) is uncertain, particularly for those with comorbid illness. Despite this uncertainty, the majority of these men currently receive local therapy. We analyzed the risk of prostate cancer-specific mortality (PCSM) relative to competing causes of mortality (CCM), stratified by disease severity and comorbidity, among contemporary men treated at two high-volume hospitals

Methods: Between 1995-2005, 4237 consecutive men aged 65 years or older were managed by radical prostatectomy (N = 1634), external-beam radiotherapy (N = 1570), or brachytherapy (N = 1033) at Cleveland Clinic or Barnes-Jewish Hospital. Clinical information was obtained from prospective data bases. Comorbidity was assessed using ACE-27 and Charlson Comorbidity indices. PC risk was classified according to D’Amico criteria. Fine and Gray competing risk analysis was used to assess PCSM and CCM at 10 years.

Results: Over a median follow-up of 72 months (IQR: 46-97), 88 and 748 PCSM and CCM events were observed. Among healthy men with low risk PC, 10 year PCSM was 2% and CCM was 19%. Among healthy men with high risk PC, PCSM was 11% and CCM was 27%. In the group with moderate-to-severe comorbidities, CCM was 49, 59%, and 58% and PCSM was 1%, 3%, and 21% among those with low-, intermediate- and high-risk PC, respectively. Among these unhealthy men, 26% were treated by radical prostatectomy, of whom 45% had low-risk PC and 16% had high-risk PC. Among healthy men, 41% were treated by radical prostatectomy, of whom 54% and 9% had low- and high-risk PC, respectively.

Conclusions: The risk of PCSM vs. CCM for older men is low, particularly for those with moderate-to-severe comorbidity; 49-59% had died from CCM within 10 years. Current evidence suggests that local therapy for PC is associated with a 25% reduction in PCSM, at best. Thus, with active surveillance, it is unlikely that PCSM would exceed 5-7% in those with low- and intermediate-risk PC. These results should inform elderly men and physicians about the risk of PCSM and CCM when deciding upon treatment for localized PC.
Long-term results of MRI-guided partial prostate brachytherapy for favorable-risk prostate cancer: Implications for focal therapy.
Authors: Nguyen Paul Linh , Chen Ming-Hui , Zhang Yuanye , Tempany Clare M. , Cormack Robert A , Beard Clair , Hurwitz Mark D , Suh W. Warren , D'Amico Anthony Victor
Published: February 2017

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Background: To report long-term results of MRI-guided partial prostate brachytherapy and propose a definition of biochemical failure following focal therapy

Methods: From 1997-2007, 318 men with cT1c, PSA < 15, Gleason ≤ 3 + 4 prostate cancer received MRI-guided brachtherapy in which only the peripheral zone was targeted. To exclude benign PSA increases due to prostatic hyperplasia, PSA failure was defined as nadir + 2 with PSA velocity >0.75 ng/mL/year. Cox multivariable analysis was used to determine factors associated with PSA failure.

Results: After a median follow-up of 5.1 years (interquartile range: 2.8 to 7.3, maximum 12.1), 26 men failed. While 36 patients met nadir+2 criteria, all eight biopsy-proven local recurrences were among the 26 men who also had a PSA velocity >0.75 ng/mL/year. On multivariable analysis, having intermediate vs. low-risk disease (adjusted HR: 4.4 [95%CI: 1.3-5.5], p<0.001) was the only factor significantly associated with an increased risk of PSA failure. PSA failure-free survival at 5 and 8 years was 95.6% and 90.0% for low risk, and was 73.0% and 66.4% for intermediate risk, respectively.

Conclusions: MRI-guided brachytherapy targeting the peripheral zone produced comparable cancer control rates to whole-gland treatment in men with PSA-detected low-risk disease, but may not be adequate for men with “favorable” intermediate-risk disease. Requiring a PSA velocity>0.75 in addition to nadir+2 may be a more appropriate way to define biochemical failure after therapies that target less than the whole gland.
Association of nuclear accumulation of p53 with ERG fusion and poor prognosis in prostate cancer.
Authors: Minner Sarah , Krohn Antje , Sirma Hueseyin , Simon Ronald , Graefen Markus , Sauter Guido , Schlomm Thorsten
Published: February 2017

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Background: We have previously shown that nuclear accumulation of p53 is rare in prostate cancer but strongly linked to early biochemical recurrence (Schlomm et al., Modern Pathology, 2008). The current study was designed to study the association between ERG fusion and p53 in a large series of prostate cancers.

Methods: A prostate cancer tissue microarray (TMA) was constructed from 4,699 radical prostatectomie specimens with histological, pathological, and clinical follow-up data. Immunohistochemistry was applied to detect nuclear p53 accumulation as a marker for defective p53 and to detect ERG expression as a surrogate for ERG gene fusion.

Results: Nuclear accumulation of p53 was detected in 62/3,667 (1.7%) analyzable tissue spots. Positive staining was significantly linked to advanced tumor stage (p<0.0001), high Gleason score (p<0.0001), presence of lymph node metastases (p=0.0005), and early PSA recurrence (p<0.0001) in all cancers. ERG expression was found in 1,990/4,266 (46.6%) analyzable cancers, but was unrelated to tumor phenotype or patient prognosis. Results of both p53 and ERG were available from 3,392 tumors. Presence of nuclear p53 staining was linked to ERG fusion positive cancers: 40 (2.7%) of 1,491 ERG-positive cancers, but only 20 (1.1%) of 1,901 ERG-negative tumors showed nuclear p53 staining (p=0.0004). A Kaplan-Meier survival analysis of p53 in the subsets of 1,699 ERG positive and 1,280 ERG negative cancers revealed that nuclear p53 accumulation was strongly linked to early PSA recurrence in both subsets (p<0.0001 each).

Conclusions: These data demonstrate that the poor prognosis of prostate cancer patients with nuclear p53 accumulation is independently from the ERG fusion status, but suggest a distinct biological role of p53 inactivation in ERG fusion positive cancers. The very high number of prostate cancer samples included in the TMA used in this study allows for analysis of rare events such as p53 alterations with high statistical power.
Effect of zoledronic acid and biochemical relapse in treatment-naive patients with bone-metastatic prostate cancer.
Authors: Matsuyama Hideyasu , Nozawa Masahiro , Inagaki Takeshi , Nagao Kazuhiro , Hara Isao , Uemura Hirotsugu ,   Kis-BoP Group
Published: February 2017

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Background: Recent reports suggest that zoledronic acid have anti-proliferative activity, and that bone metabolism markers predict patient outcome in prostate cancer. Aims of this study are if bone metabolism markers may predict patient outcome who are treated with zoledronic acid concomitant with androgen deprivation therapy (ADT), and if zoledronic acid has oncological benefit in patients with metastatic prostate cancer.

Methods: A multi-institutional prospective phase II study was conducted for 54 treatment-naïve patients with bone-metastatic prostate cancer who were treated with zoledronic acid concomitant with ADT (ADT-Z group). Median age, baseline PSA of the patients were 72, and 249ng/ml, respectively. Patients were treated with zoledronic acid (4 mg iv every 4 weeks) in combination with bicalutamide (80mg po) and goserelin acetate (10.8mg sc every 3 months), and followed with a median follow-up of 24.6 months. Serum bone metabolism markers, including bone-specific alkaline phosphatase (BAP) and cross-linked C-terminal telopeptides of type I collagen (I-CTP) and urine levels of cross-linked N-terminal telopeptides of type I collagen (NTx), were measured before treatment followed by every 3 months thereafter, and were compared with biochemical relapse (BCR). BCR of those patients was compared with that of 180 patients who were treated with ADT alone (ADT group) as historical control.

Results: Baseline NTx (>100), baseline PSA (>225), EOD (>2) were significantly linked with BCR. Baseline NTx (>100) was an independent predictor for BCR in multivariate analysis (p=0.02). Time to BCR was significantly longer in ADT-Z group than that in ADT group (p<0.0001, median TTP: not reached in ADT-Z vs. 15.4 months in ADT).

Conclusions: Zoledronic acid may improve patient prognosis, and baseline NTx may be a useful predictor for BCR in treatment-naïve metastatic prostate cancer patients with zoledronic acid combined with ADT.
Diet, supplements, and lifestyle factors and risk of progression in contemporary active surveillance patients.
Authors: Trock Bruce J. , Feng Zhaoyong , Landis Patricia , Carter Ballentine
Published: February 2017

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Background: Men diagnosed with prostate cancer frequently change their diet or lifestyle in an effort to decrease their risk of developing aggressive disease. Men managed with active surveillance (AS) may feel a greater need to modify risk factors because their cancer is untreated. However, no data on post-diagnosis diet and lifestyle factors from large prospective cohorts with long-term follow-up have been reported. We evaluated the influence of diet and lifestyle on the risk of prostate cancer biopsy progression in the largest prospective AS cohort in the US.

Methods: Diet and lifestyle questionnaire completed by AS participants at enrollment. Progression determined by occurrence of Gleason score>7 or increase in tumor volume at annual surveillance biopsy. Analysis focused on 28 nutrients, 10 food groups, 9 supplements, 7 medication variables, and 2 lifestyle variables with a priori hypotheses. Data were analyzed by Wilcoxen test and logistic regression, with calorie adjustment by the residual method.

Results: There were 723 men in the analysis, of whom 187 (26%) progressed. Median follow-up was 2.7 years. Men who progressed were significantly older, had higher PSA density, and higher biopsy tumor burden at diagnosis. In multivariable analyses, men who progressed had higher PSA density (OR=1.34 per 0.1 ng/ml/cc, p=0.017), were more likely to have >1 positive biopsy core (OR=2.9, p<0.0001), had higher percentage core involved with tumor (OR=1.04, p<0.0001), and were more likely to be current smokers (OR=4.1, p=0.004); duration of NSAID use and history of prostatitis approached significance.

Conclusions: Cigarette smoking was significantly associated with risk of progression. This association must be viewed with caution due to the large number of variables tested. It is likely that many men considered to have progressed represent undersampling of the initial biopsy, rather than true biologic progression; this misclassification may obscure risk relationships. Ongoing analyses will be presented that explore whether associations differ for early vs late progression events. We believe this is the first report that smoking is associated with progression in men managed by AS.