bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of short course radiation followed by four cycles of FOLFOX as preoperative therapy for rectal cancer on rate of PCR: A phase II trial.
Authors: Myerson Robert J. , Parikh Parag J. , Hunt Steven R. , Tan Benjamin
Published: February 2017

471

Background: Preoperative radiotherapy (RT) with 5FU chemotherapy (CT) is a standard of care for cT3-4 rectal cancer. Studies incorporating additional cytotoxic agents have resulted in increased morbidity with little benefit. We evaluate a template that seeks to (1) include the benefits of preoperative RT on local response/control, (2) provide preoperative multi-drug CT, (3) avoid the morbidity of concurrent RT and multi-drug CT. Methods: Patients with cT3-4, any N, any M rectal cancer were eligible. Patients were confirmed to be candidates for surgery, provided the response was sufficient. Preoperative treatment was 5 fractions RT (25 Gy to involved mesorectum, 20 Gy to elective nodes), followed by 4 cycles of mFOLFOX6. Postoperative CT was at the discretion of the medical oncologist. The principal objectives were to achieve T stage down staging (ypT < cT) and acute grade 3+ gastrointestinal (GI) morbidity equal or better than historic controls. Results: 80 patients were enrolled from 11/2009 through 4/2012. All have had sufficient time for principal endpoint analysis. Four are inevaluable for response: 1 patient withdrew consent after completing RT and never received CT and 3 did not undergo surgery (new comorbidity in 2 cases, progression of distant metastatic disease in 1 case). Grade 3 preoperative GI morbidity occurred in 7 cases (9%) (no grade 4 or 5). The 76 evaluable cases included 7 cT4 and 69 cT3; 59 (78%) cN+, 8 cM1. Sphincter preserving surgery was performed on 49 (64%) cases. At surgery 53 (70%) had ypT0-2 residual disease including 21 (28%) ypT0; 24 (32%) were ypN+. For M0 evaluable cases 2 year NED survival is 91+/-6% with no local failures. Cases were sub-analyzed by whether disease met requirements for the recently activated ACOSOG preoperative FOLFOX vs. 5FU-RT trial. Thirty eight cases met ACOSOG eligibility and achieved 16 ypT0 (42%) and 33 ypT0-2 (87%). Conclusions: This regimen achieved high response and low morbidity rates that compare favorably with conventionally fractionated RT and concurrent CT. The ongoing RAPIDO trial compares a similar regimen to conventional chemoradiation in poor risk locally advanced rectal cancer patients.
Uptake of adjuvant chemotherapy for colon cancer in older and younger patients in the Irish population.
Authors: Coyle Seamus , Rehman Zia , Lee Chalen , Deady Sandra , Comber Harry , O'Connor Miriam , Calvert Paula , Horgan Anne M
Published: February 2017

478

Background: Colon cancer is predominantly a disease of the elderly, with recent evidence supporting the use of adjuvant chemotherapy in the older population. However, it remains unclear to what degree such patients are receiving adjuvant therapy in clinical practice. We examined uptake of adjuvantchemotherapy and it’s impact on survival in older patients with stage II and stage III colon cancer in a national cohort. Methods: Using the National cancer Registry of Ireland, we identified 3,486 patients with stage II and III colon cancer who were treated with curative resection from 2004-2009. Clinopathological features and chemotherapy use were compared between those ≥70 years and those < 70 years. Results: A total of 2,026 patients with stage II disease were identified, 56% male and 60% ≥ 70 years. T3 tumors accounted for 81%, T4 19% and 89% were grade 2/3. Adjuvant chemotherapy was utilized in 10% and 40% of ≥ 70 and <70 years, respectively (p<0.0001). A benefit for chemotherapy over observation alone was seen in both the older [HR 0.36; 95% CI 0.36 – 0.68; p <0.0001] and younger patient groups [HR 0.43; 95% CI 0.2701 - 0.6881; p<0.0004]. Of 1,460 patients with stage III disease, 51% were ≥ 70 years, 54% male. 34% of older and 83% of younger patients received adjuvant therapy (p<0.0001). A similar magnitude of benefit from chemotherapy compared to observation was seen in patients ≥ 70 years [HR 0.30; 95% CI 0.29 - 0.45 ; p <0.0001] and <70 years [HR 0.22 95%CI 0.1 – 0.2; p<0.0001] with stage III disease. Conclusions: Adoption of adjuvant chemotherapy appears to be associated with significant survival benefit in older patients (age ≥ 70 years), however, is still underutilized in clinical practice. The impact of sociodemographic and clinicopathological features as potential drivers of treatment decisions in a cohort of this population will be reported.
Biomarker distribution and characteristics for the first 100 patients in MAVERICC, a randomized phase II study of mFOLFOX6-bevacizumab (BV) versus FOLFIRI-BV in previously untreated metastatic colorectal cancer (mCRC).
Authors: Starodub Alexander , Thomas Sachdev P. , Lee Fa-Chyi , Harish Vallathucherry , Koh Han A. , Mitchell Edith P. , Mandanas Romeo Ang , Huh Sang Y. , Badarinath Suprith , Mittan Angelique , Leon Larry , Vogt Tobias , Langer Christiane , Lenz Heinz-Josef
Published: February 2017

483^

Background: Retrospective analyses have suggested that ERCC1 is a chemo-resistance marker to platinum compounds; a median tumoral ERCC1 level of 1.7 × 10–3ERCC1/β-actin mRNA has been reported in metastatic colon cancer (Grimminger et al, Pharmacogenomics J, 2011). MAVERICC is the first prospective study of tumoral ERCC1and plasma VEGF-A as potential biomarkers for oxaliplatin- and BV-containing regimens, respectively. We present data from a planned interim biomarker distribution assessment of the first 100 patients (pts) in MAVERICC. Methods: In this randomized, open-label, phase II study, pts (N=360) with histologically or cytologically confirmed CRC and ≥1 measurable metastatic lesion are stratified at screening by tumoral ERCC1 mRNA expression (low vs high, cutoff of ≤ vs >1.7). Stratified pts are randomized 1:1 to mFOLFOX6-BV or FOLFIRI-BV administered in 2-week cycles. The primary objectives are: 1) to assess ERCC1 and VEGF-A as biomarkers of progression-free survival (PFS) for oxaliplatin- and BV-containing 1st-line regimens, and 2) within ERCC1 high pts, to test whether FOLFIRI-BV is associated with a prolonged 1st-line PFS vs mFOLFOX6-BV. Results: With a data cutoff of June 19 2012, 100 pts have been enrolled. Of these, 75 pts were stratified to the ERCC1 high group and 25 pts to the ERCC1 low group. The median ERCC1 mRNA expression was 3.00 (range, 1.73–13.16) and 1.32 (range, 0.70–1.70) in the ERCC1 high and low stratification groups, respectively. Among all pts, the median ERCC1 mRNA expression was 2.37. Pt demographics by group are shown (Table). Plasma VEGF-A evaluation is ongoing. Conclusions: An analysis of the first 100 pts in MAVERICC showed that the median tumoral ERCC1 expression level was higher than the predefined cutoff, providing an adequate population of ERCC1 high pts to assess PFS by treatment regimen. Clinical trial information: NCT01374425. [Table: see text]
Metastatic colorectal cancer (mCRC) with primary in situ: An Australian registry.
Authors: Wong Shu Fen , Field Kathryn M , Kosmider Suzanne , Tie Jeanne , Wong Hui-Li , Tran Ben , Tacey Mark , Shapiro Jeremy David , McKendrick Joseph J , Gibbs Peter
Published: February 2017

498

Background: The role of primary tumor resection in patients presenting with mCRC remains controversial. While recent data suggest resection of the primary tumor is unnecessary with modern systemic therapies, other series indicate that non-operative intervention may be associated with inferior survival outcomes. We aimed to evaluate the Australian approach to primary tumor resection in patients with mCRC and to explore its impact on survival outcomes. Methods: This study was conducted using a clinician-designed mCRC registry involving 15 participating Australian sites. Patients were excluded if planned for curative resection of metastatic disease or had incomplete data. Cox logistic regression analyses were used to identify and quantify associations between overall survival (OS) and patient/clinical variables. Results: We identified 533 mCRC patients with median follow up 12.5 mo. 41% (n=220) had their primary in-situ. Rates of primary tumor resection were higher in older patients (>70 yrs old) (64.5% vs 52.7%; p=0.006), colon versus rectal primaries (64.6% vs 42.7%; p<0.001) and those without liver metastases (70.7% vs 52.9%; p<0.001). Median OS was significantly better in patients undergoing primary tumor resection compared to the non-resected population (28.3 mo vs 15.9 mo; Hazard Ratio (HR): 0.52; log-rank p<0.001). Univariate analyses indicate that older age (HR: 1.69; p<0.001), poor performance status (HR: 4.44; p<0.001) and peritoneal involvement (HR: 1.94; p<0.001) were associated with poorer survival outcomes while chemotherapy administration (HR: 0.33; p<0.001) predicted improved survival. Multivariate analyses, when adjusted for known prognostic factors, confirms that primary tumor resection remains an independent predictor of better survival (HR: 0.50; p<0.001). Conclusions: The 41% of primary cancers in-situ is higher than previous mCRC studies and suggests a tendency for non-operative intervention in Australia. Given the survival outcomes demonstrated in this study, a review of Australian clinical practice is required. Future studies will examine the survival differences in patients with de novo versus relapsed metastatic disease, motivation for resection and other confounding variables.
A multicenter phase I study on preoperative chemoradiotherapy with S-1 and CPT-11 for locally advanced lower rectal cancer (SAMRAI-1).
Authors: Noda Masafumi , Sato Takeo , Hayakawa Kazushige , Tomita Naohiro , Kamikonya Norihiko , Ishihara Soichiro , Kato Daiki , Sakai Yoshiharu , Hiraoka Masahiro , Shimada Mitsuo , Ikushima Hitoshi , Baba Hideo , Oya Natsuo , Oya Masatoshi , Oguchi Masahiko , Takeuchi Masahiro , Watanabe Masahiko
Published: February 2017

503

Background: Preoperative chemoradiotherapy with 5-FU is a standard therapy for locally advanced lower rectal cancer. This therapy is useful for increasing local control rates and maintaining anal functions, but there is no evidence indicating that this therapy can extend survival. We performed a phase I study with the objective of developing a new chemoradiotherapy with irinotecan (CPT-11) and S-1, containing gimeracil, a dihydropyrimidine dehydrogenase inhibitor with radiosensitizing effect. Methods: Patients with locally advanced lower rectal cancer (T3-4, N0-2) of which the inferior border was located closer to the anal verge than to the peritoneal reflection were used for analysis. The radiation dose was 45 Gy in 25 fractions. The radiation field included the internal iliac, pararectal, and obturator lymph nodes in addition to the primary tumor and enlarged lymph nodes. S-1 was administered for five consecutive days and withdrawn for two consecutive days (administration: Days 1-5, 8-12, 22-26, and 29-33). The dose of S-1 (80, 100, 120 mg/day) was controlled in accordance with the body surface area. CPT-11 was administered on days 1, 8, 22, and 29. The initial dose of CPT-11 was 60 mg/m2 (Level 1), and the dose was increased gradually. Total mesorectal excision was performed 6-10 weeks after completion of the chemoradiotherapy. Results: 20 patients were enrolled. Excluding 2 patients who discontinued the study, 18 patients were subject to analysis. Dose-limiting toxicity (DLT) was not seen in 3 patients treated with CPT-11 at 80 mg/m2 (Level 2), but was seen in 3 of the 6 patients treated with CPT-11 at 90 mg/m2 (Level 3). DLT was seen in 3 other patients administered a Level 2 dose. At Level 2 or Level 3, DLTs, namely neutropenia, thrombocytopenia and diarrhea were seen. Level 2 was regarded as a maximum tolerated dose, and Level 1 as a recommended dose (RD). The pathological complete response rate was 28%, and the downstaging rate 56%. Conclusions: The results of the study suggest that the RD of CPT-11 is 60 mg/m2. We plan to perform a phase II study to evaluate the efficacy and safety of chemoradiotherapy with S-1 and CPT-11. Clinical trial information: UMIN000001639.
Are the numbers of retrieved lymph nodes (LNs) within and outside the radiation field significant prognostic factors in patients who received chemoradiotherapy (CRT)?
Authors: Okada Kazutake , Sadahiro Sotaro , Suzuki Toshiyuki , Tanaka Akira , Kamijo Akemi
Published: February 2017

510

Background: We had presented last year that the number of lymph nodes (LNs) significantly decreased within the radiation field, but not outside the radiation field in rectal cancer patients who received preoperative chemoradiotherapy (CRT) as compared with patients who underwent surgery alone. In the present study, we examined the relation between survival and the number of LNs within and outside the radiation field, separately. Methods: The study group comprised 210 patients who underwent radical surgery for clinical stage II or III rectal cancer from 1991 through 2010. A total of 108 patients underwent surgery alone (S group), and 102 patients received preoperative CRT, 40 or 45 Gy with concurrent oral UFT or S-1, (CRT group). LNs were divided into two groups according to their distribution; within the radiation field (within the mesorectum) or outside the radiation field. Results: Patient demographics did not differ between the groups. The number of LNs examined was 2617, of which 290 (11%) were metastatic. The mean total number of LNs was significantly higher in the S group (16 ± 11) than in the CRT group (9 ± 7; p<0.01). The number of LNs within the radiation field was significantly higher in the S group (6 ± 6) than in the CRT group (4 ± 4; p<0.01), but the number of LNs outside the radiation field did not differ. The total number and the number of metastatic LNs outside the radiation field did not differ between the groups, however, the number of metastatic LNs within the radiation field was significantly higher in the CRT group (S group, 2 ± 2; CRT group, 3 ± 4; p<0.01). In the S group, the total number of LNs and the number of LNs within the mesorectum were both prognostic factors in pStage II disease. A total number of ≥18 LNs and ≥5 LNs within the mesorectum were associated significantly with better outcomes. The number of metastatic LNs within the mesorectum was a prognostic factor in pStage III disease. In the CRT group, however, the total number of LNs and the number of LNs within the mesorectum were not related to survival. Conclusions: The number of LNs within the mesorectum might be a prognostic factor in patients who receive surgery alone, but not in patients who receive CRT.
Association of mucin production and survival in colon cancer.
Authors: Hogan John , Samaha Georges , Burke John , Waldron David , Condon Eoin , Coffey John Calvin
Published: February 2017

512

Background: Debate persists regarding the relationship between mucin production and cancer-related outcome following curative resection for colon cancer. Lack of consensus is due to (amongst other factors) discrepancies in definition, small cohort studies and the integration of both colon and rectal cancers. This study characterizes the relationship between mucin production and cancer-related outcome in an homogenous single-institute based cohort. Methods: A database spanning demographics, clinico-pathologic characteristics and prognostic factors was generated for all patients undergoing curative-intent colonic resection in the interval 2000 to 2010. Patients were categorized simply as mucin producing (i.e. MC) or non-mucin producing adenocarcinoma (NMC). Primary outcomes included overall survival (time to death from any cause) and disease free survival (time to loco-regional and systemic recurrence). Trends were established for MC and NMC using Kaplan-Meier estimates, plotted and compared using log-rank analysis. Findings significant on univariate analysis were incorporated into multivariate analysis. Cox proportional hazards model was employed to determine the associated hazard of both death and disease recurrence in each group. Statistical analysis was performed using R version 2.15. P < 0.05 was considered significant. Results: 77 mucinous carcinomas (MC) and 358 non mucinous carcinomas (NMC) were included. On univariate analysis, MC was associated with improved overall survival (OS) (P=0.007). Both N1 (HR 1.625, P=0.011) and N2 (HR 2.7, P<0.001) status were associated with adverse OS. On multivariate analysis, MC approached but did not reach statistical significance for improved OS (HR 0.543, P=0.061). A comparison of Kaplan-Meier estimates for overall survival in MC and NMC groups indicated that OS was significantly improved in the MC cohort (P=0.011). There was no difference in disease free survival (P=0.224). Systemic recurrence was greater in the NMC group (P=0.042). Conclusions: Mucin production in colonic adenocarcinoma appears associated with improved overall but not disease-free survival. In addition, the absence of mucin was associated with adverse systemic but not local recurrence.
Impact of smoking history on patient outcome following hepatic metastasectomy for colorectal cancer.
Authors: Shen Yehua , Sahin Ibrahim Halil , Hassan Manal , Kee Bryan K. , Feig Barry W. , Ellis Lee M. , Aloia Thomas A. , Abdalla Eddie K. , Curley Steven A. , Vauthey Jean-Nicolas , Garrett Chris R.
Published: February 2017

517

Background: Although it is clear that smoking increases perioperative risks associated with liver resection, there are also oncologic concerns associated with smoking. For example, nicotine induces CRC cell proliferation in vitro. We undertook a single institution retrospective analysis of pts outcome based on prior smoking history. Methods: Under an IRB-approved protocol, pts who underwent hepatic metastasectomy for treatment for CRC liver metastasis with curative intent at a single institution, from 2005 to 2009, were retrospectively evaluated for smoking history, time to progression (TTP), and overall survival (OS). Pts were analyzed as never smokers (A), ex-smokers (B), or current smokers and those who discontinued at the time of cancer diagnosis (C). Results: 350 pts outcomes were analyzed; their data is demonstrated in the table below. There were no difference in TTP or OS between group A and B (p = 0.346, p = 0.453 respectively). Pts in group A had a superior TTP and OS when compared to group C (p =0.002, p = 0.021 respectively). Patients in group B had a superior TTP when compared to group C (p =0.044), while a difference of OS was not found between the two groups (p =0.153). Conclusions: Smoking history is a negative prognostic factor for TTP in patients undergoing hepatic metastasecomy for CRC. Further studies are necessary to validate these preliminary findings. Active smokers who are candidates for hepatic metastasectomy for CRC should undergo nicotine cessation counseling and treatment. [Table: see text]
Survival differences in patients (pts) with resected rectal cancer who received neoadjuvant therapy with or without postoperative chemotherapy (CT).
Authors: Wu Christina Sing-Ying , Wei Lai , Glass Katherine , Wilson John , Abdel-Misih Sherif , Martin Ludmila Katherine , Haraldsdottir Sigurdis , Harzman Alan , Husain Syed , Schmidt Carl Richard , Arnold Mark , Goldberg Richard M. , Bekaii-Saab Tanios S.
Published: February 2017

518

Background: Pts with stage II/III rectal cancers are treated with neoadjuvant chemoradiation and surgical resection followed by adjuvant CT per practice guidelines. It is unclear whether adjuvant CT provides survival benefit, and the purpose of this study was to measure outcome in pts who did and did not receive adjuvant CT. Methods: We used a prospectively collected database for pts treated at The Ohio State University, and analyzed overall survival (OS), time to recurrence (TTR), pt characteristics, tumor features, and treatments. Survival curves were estimated using Kaplan-Meier method and compared by the log-rank test. Age was compared using the Wilcoxon test, and other categorical variables were compared using Chi-square test or Fisher’s exact test. Results: Between August 2005 to July 2011, 110 pts were identified and 71 pts had received adjuvant CT. There was no significant difference in sex, race, pathologic tumor (T) stage, and pathologic complete response between the two pt groups. Pts receiving adjuvant CT were significantly younger (median age 54.3 vs. 62 years, p=0.01) and had more advanced pathologic nodal (N) stage (43 vs. 19%, p=0.02). Median OS was 72.6 months with CT vs. 36.4 months without CT (p=0.0003). Median TTR has not yet been reached. Conclusions: In this retrospective analysis, adjuvant CT was associated with a longer OS despite more advanced pathologic nodal staging. Prospective randomized studies are warranted to determine whether adjuvant CT provides a survival benefit for pts across the spectrum of stage II and III rectal cancer. [Table: see text]
Intensity-modulated radiation therapy (imrt) for anal cancer: Results from a multi-institutional retrospective cohort study.
Authors: Call Jason Andrew , Prendergast Brendan M , Jensen Lindsay G , Ord Celine B , Goodman Karyn A. , Jacob Rojymon , Mell Loren K. , Thomas Charles R. , Jabbour Salma , Miller Robert Clell
Published: February 2017

523

Background: This study was done to assess the toxicity and efficacy of IMRT for anal cancer in a multi-institutional setting. Methods: Records of 152 total patients (pts) were reviewed retrospectively. Data on disease control and toxicity were collected as well as pt and treatment characteristics. Acute (<6 months) and late (>=6 months) severe toxicity (grade >=3) were recorded at each institution. Four were excluded for either presence of metastatic disease (2) or stage TX (2). There was data for late toxicity on 120 pts. Results: T stage was T1 in 28, T2 in 79, T3 in 29 and T4 in 12 pts. N stage was N0 in 77, N1 in 40, N2 in 19 and N3 in 12 pts. The median age was 56 yrs and median follow-up was 26.8 months. Cumulative IMRT dose was 51.25 Gy (median) (range: 4.32-61.2 Gy) in a median of 28 fractions (2-34). Chemotherapy was given in all but 2 pts and the most common regimen was 5- fluorouracil plus mitomycin-C. The median total elapsed treatment time was 40 days. Local control at 3 yrs was 87% and was significantly worse for patients with T3-4 disease (79% vs 90% at 3 years; p=0.04). There was no correlation between dose and local control. Regional control, distant control and overall survival were 97%, 91%, and 87% at 3 yrs, respectively. Nodal status was associated with regional and distal control as well as overall survival (p<0.01 for each). The most common acute severe toxicity was hematologic (41%). Severe acute GI, skin or other toxicity was 11%, 20% and 1% respectively. There were two grade 5 toxicities (hematologic and GI). Severe late toxicity was limited to skin (1%) and GI (3%). Conclusions: IMRT resulted in excellent local control in this multi-institutional cohort of pts. Although T stage did predict for worse local control, most pts with T3-4 disease were controlled with IMRT. Nodal status predicts for regional and distal control as well as overall survival. Severe toxicity was acceptable with this technique.
Final report of post-marketing survey of panitumumab in Japanese patients with unresectable advanced or recurrent colorectal cancer.
Authors: Hamaguchi Tetsuya , Boku Narikazu , Sugihara Kenichi , Kitagawa Yuko , Takiuchi Hiroya , Hatake Kiyohiko , Muro Kei , Yoshino Takayuki , Yamazaki Naoya , Gemma Akihiko , Yana Ikuo , Ueno Hiroshi , Ohtsu Atsushi
Published: February 2017

525

Background: Panitumumab (P-mab) was approved in Japan in Apr. 2010 for the treatment of unresectable, advanced or recurrent colorectal cancer with wild-type KRAS, both in monotherapy and in combination with chemotherapy for all lines of treatment. All-case surveillance of P-mab was conducted to assess safety and efficacy in practical use since clinical data on Japanese patients were limited. Methods: All patients were registered before starting P-mab containing therapy by central registration method since the launch of P-mab in Japan. Patients were examined for eligibility requirements such as KRAS genotype (wild), ECOG PS (0-2) and interstitial pneumonitis (-). Skin disorder, infusion reaction(IR), electrolyte abnormality, cardiac disorder, interstitial lung disease (ILD) were surveyed with special interest. Results: 3,091 patients were registered from Jun. 2010 to Nov. 2010 and interim analysis were made with 3,005 patients at the point of Oct. 2011. The interim analysis; male: 63.6%, mean age: 65 y.o., KRAS wild/ mutant/ not determinable: 97.3%/0.1%/2.6%. Proportion of first line/second line/third line or later treatment: 10.4%/18.0%/71.6%, PS 0-1/2/3/4: 91.3%/7.9%/0.7%/0.1%. P-mab monotherapy/combination: 41.0%/58.8%. Combination regimens: FOLFOX/FOLFIRI/other regimens: 18.7%/33.4%/15.2%. Overall incidence of ADRs:83.7 %, and that of Grade 3 or higher ADRs:24.7 %. Incidence of ADRs of special interest: skin disorder 77.8%, IR 1.5%, electrolyte abnormality18.3%, cardiac disorder 0.2%, ILD 1.3% (0.6% fatal). Incidences of ILD were similar in monotherapy and in combination. The median survival time of patients with P-mab monotherapy as third line or later treatment was 10.3 months, 95%CI (9.0-11.3). Result of final analysis with 3086 patients(99.8% of registerd patients) at the point of Jun. 2012 is to be presented in this meeting. Conclusions: The safety profile of P-mab in the post-marketing use was similar to that previously reported in the clinical trials. The risk/benefit balance for use of P-mab in patients with unresectable colorectal cancer remains favorable.
Phase II study of S-1 plus leucovorin (1-week treatment regimen followed by 1-week rest period) in patients with untreated metastatic colorectal cancer in Japan and China: Comparing results of each country and updating overall survival.
Authors: Xu Ruihua , Li Jin , Xu Jianming , Denda Tadamichi , Ikejiri Koji , Shen Lin , Baba Hideo , Toh Yasushi , Shimada Ken , Kato Takeshi , Sakai Kenji , Matsuyama Ayumi , Mishima Hideyuki , Wang Jin-Wan
Published: February 2017

528

Background: We previously reported results of a phase II study of the S-1 plus oral Leucovorin(LV) (1 week on/ 1 week off) for patients (pts) with metastatic Colorectal Cancer (mCRC) (Denda et al. Gastrointestinal Cancers Symposium 2012). This study showed promising activity in pts with mCRC. We report here the comparison of efficacy and safety data of each country, and updated Overall Survival (OS). Methods: Pts were eligible as follows: histologically confirmed adenocarcinoma, age ≥20, ECOG PS 0-1, no prior chemotherapy, at least one measurable lesion by RECIST ver1.0 criteria, adequate organ function, and written informed consent. S-1 (40-60 mg bid) and LV (25 mg bid) were orally administered for 1 week, followed by 1 week rest period. The treatment was repeated until disease progression or unacceptable adverse events. The primary endpoint was the response rate (RR), and the secondary endpoints were efficacy and safety. This trial was supported by Taiho Pharmaceutical CO., LTD. ClinicalTrials.gov Identifier: NCT00891332 Results: From October 2008 to June 2009, 73 pts were enrolled in Japan and China. Of the eligible 71 pts, Japan/China was 32/39; median age was 60 (range 27-84); Male/Female was 38/33, and PS:0/1 was 39/32. RR as primary endpoint was 53.5% (95% CI, 41.3-65.5), and 59.4% in Japan and 48.7%in China; Progression Free Survival(PFS) in Japan and China was 6.3 and 6.8 months; median OS was 29.0 and 20.8 months, respectively. The incidences of grade 3 adverse drug reactions were diarrhea 8.3% (3.1% in Japan, 12.5% in China), stomatitis 8.3% (12.5% and 5.0%), anorexia 2.8% (6.3% and 0.0%), neutropenia 9.7%(9.4% and 10.0%), and there was no treatment-related death. Conclusions: This S-1 plus LV (1week on/ 1 week off) treatment regimen showed promising activity in pts with untreated mCRC without the concurrent use of irinotecan, oxaliplatin, or molecular-targeted drugs in both Japan and China. Clinical trial information: NCT00891332.
American medical oncology physician (AMOP) preferences for combined modality therapy beginning with systemic management in patients with liver-limited metastatic colorectal cancer (LL-mCRC).
Authors: Choti Michael A. , Green Mark R. , Corral Mitra , Wong Schiffon L. , Cairns Jessica , Thomas Michele R. , Eaddy Michael
Published: February 2017

532

Background: Patients with LL-mCRC are frequently managed with multi-modality therapy, including systemic chemotherapy ± biotherapy. In some settings, surgery is used first followed by systemic therapy. In others, the systemic therapy may be used for initial cytoreduction of both macro- and micro-metastatic disease with surgical consolidation and then observation or further systemic management post-operatively. In the current study, we assessed the preferences of 190 AMOPs in the treatment of patients with LL-mCRC. Methods: AMOPs practicing for ≥5 years and ≤35 years with ≥70% direct patient contact were eligible for study inclusion. To assess preferred sequencing, a single patient profile was created and 10 different sets of de-identified liver CT l images representing a broad spectrum of LL-mCRC were collected. AMOPs independently reviewed each set of liver CT images through a web-based tool and provided their assessment of the immediate resectability of the LL-mCRC shown, as well as their preferred approach to the initial management for that set of scans. Treatment preferences across all scans were presented according to the percentage of AMOPs designating a particular scan as resectable now. Results: Participating AMOPs treated an average of 15.5 mCRC patients per month. Resectability rates and preferences for initial therapy are shown in the Table. Conclusions: AMOPs show an overall preference for initiation of sequencing multi-modality management with systemic therapy across the spectrum of LL-mCRC. [Table: see text]
Obesity and peritoneal surface disease: Outcomes following cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC).
Authors: Votanopoulos Konstantinos I , Swett Katrina R , Swords Doug S , Shen Perry , Stewart John , Levine Edward A.
Published: February 2017

533

Background: It is estimated that 35% of the US population is obese. It is unknown how obesity influences the operative and survival outcomes of CRS/HIPEC procedures. Methods: A retrospective analysis of a prospective database of 1,000 procedures was performed. Type of malignancy, ECOG, resection status, hospital and ICU stay, Clavien-Dindo morbidity, mortality and survival were reviewed. Results: 242 patients with BMI>30 (30-63.3) underwent 264 CRS/HIPEC procedures between 1991-2012. 94(38.8%) of those had a BMI>35. 136(51.7%) obese patients had appendiceal and 59(22.4%) colon cancer. Median follow up for obese patients was 52 months. Major (III /IV) and minor morbidity (I/II) was 36.6% and 28.8% for obese and 36.5% and 25.7% for non-obese patients. The 30 day mortality for obese and non-obese was 5.5% and 7.3% respectively. Median ICU and hospital stay was 1 and 9 days for both obese and non-obese. The 30 day readmission rate was similar between obese and non-obese patients 35.2% vs 30.8%. When patients were grouped by primary (colon or appendix), resection status, and grade of disease (for appendiceal) and stratified by BMI (not obese, 30-<35, ≥35) there was no difference in 30 day postoperative morbidity and mortality. When the interaction of obesity with the biology of the underlying primary was studied there was no obesity related survival differences. For obese and non-obese patients, median survival for low grade appendiceal cancer was 76 months and 107 months respectively (p=0.38) and for colon cancer was 18.1 months and 19.8 months. 5 and 10 year survival for the low grade appendiceal group was 60.5% and 33.1% for obese and 69.1% and 46.5% for non obese (p=0.38). Conclusions: Obesity does not influence postoperative morbidity and mortality of patients with peritoneal surface disease (PSD) regardless of primary. Obesity does not influence long term survival for appendiceal and colon cancer patients with PSD, and should not be considered a contraindication for the procedure.
Positron emission tomography-computed tomography (PET-CT) for the assessment of pathologic response to neoadjuvant chemoradiotherapy in rectal adenocarcinoma.
Authors: Ashraf Noman , Razzaque Saqib , Creelan Ben C. , Chavez Julio C. , Shibata David , Hoffe Sarah , Shridhar Ravi , Kim Richard D.
Published: February 2017

537

Background: Preoperative 5-fluorouracil and radiation (FU-XRT) has been demonstrated to improve recurrence-free survival in locally advanced rectal adenocarcinoma, however the role of interval PET-CT remains unclear. We performed a retrospective study with the primary objective of examining the association of change in standardized uptake value (SUV) by PET-CT after neoadjuvant chemoradiation and pathologic complete response (path CR) to survival. Methods: Data was extracted for cases at our institution between August 2006–August 2009, with last follow-up performed July 2012. Patients were included if (i) they had completed a full course of preoperative FU-XRT, followed by surgery with intent for R0 resection, and (ii) pre- and post- therapy PET-CT as well as pathologic reports were available for review. Data was compared by Fischer's exact and Wilcoxon rank-sum, and survival was analyzed using Kaplan-Meier method. Clinicopathologic data was compared by log-rank test and univariate Cox proportional hazards for relationship to overall survival (OS). Results: Of 128 total rectal cancer cases reviewed, 25 (19%) met inclusion criteria. Characteristics of 25 patients included: 13 female, age 57± 14 years (median ± SD). After 116 patient-years of follow-up, median OS was not reached; mean OS was 4.6 ± 0.9 years. Mean baseline pre-treatment PET SUV (18.5 ± 9.1) decreased after neoadjuvant FU-XRT (5.0 ± 4.3, p < 0.0001). Five achieved path CR. Presence of earlier stage was associated with non-significant trend towards improved chance of pathologic CR (RR 3.1, p = 0.07). A decrease in PET SUV by 80% or more was associated with improved odds of path CR (OR 25, 95% CI 1.2 - 513, p = 0.009), and was also associated with a non-significant trend towards improved OS (HR 0.19, 95% CI 0.01 - 2.7). Path CR was associated with a non-statistically significant trend to improved overall survival (HR 0.28, 95% CI 0.01 - 8.4). Conclusions: Reduction in PET-CT SUV after neoadjuvant chemoradiation may be a useful predictor of pathologic CR in rectal adenocarcinoma. These exploratory findings need to be validated in larger prospective studies.
Efficacy of carboplatin and paclitaxel therapy in patients with advanced squamous cell carcinoma (SCC) of the anal canal.
Authors: Byer Jennifer , Mahipal Amit , Dinwoodie William R. , Almhanna Khaldoun , Shibata David , Kim Richard D.
Published: February 2017

539

Background: Development of distant metastases in SCC of the anal canal is not very common after treatment with combined modality. Only widely published data for treatment of metastatic disease is cisplatin and 5-FU. Carboplatin and paclitaxel is commonly used in squamous cancer of the lung but its efficacy in SCC of the anal cancer is unclear. The objective of this study is to determine the tolerability and outcome of patients with SCC of the anal canal treated with carboplatin/paclitaxel at Moffitt Cancer Center. Methods: Retrospective analysis was conducted looking at Moffitt Cancer tumor registry from 1/2007 to 1/2012. Eligible patients were required to have diagnosis of SCC of the anal cancer and received carboplatin/paclitaxel every 3 weeks as part of the treatment. Results: 13 patients fulfilled the criteria. 11 patients were initially diagnosed with early stage (Stage I-III). 11 patients received concurrent chemo radiation (Nigro regimen or cisplatin + 5-FU) and had reoccurrence. 2 patients were initially diagnosed with Stage IV disease. Median age was 56 years and 77% were females. Upon diagnosis of metastatic disease, 11 patients received prior chemotherapy (cisplatin/5FU, irinotecan/cetuximab, cisplatin/docetaxel). 4/13 patients received 2 prior chemotherapy regimens, 7/13 received only 1 prior regimen and 2/13 did not receive any prior chemotherapy. Patients received an average of 4.7 cycles (1 cycle= 3 weeks). Median was 4 cycles. The response rate was high at 62% with 2 patients achieving complete response and 6 patients with partial response. Grade 3 toxicities included peripheral neuropathy (n= 3), diarrhea (n= 1), and infection (n=3). 4 patients had grade 3 neutropenia and 1 patient had grade 4 anemia. Median progression free survival and overall survival were 4.6 and 10.5 months respectively. Conclusions: Carboplatin and paclitaxel seem to be well tolerated and have activity in the treatment of advanced SCC of the anal canal. Larger studies need to be conducted to validate these findings.
Retrospective cohort study on the safety and efficacy of panitumumab for patients with metastatic colorectal cancer: The HGCSG1002 study—Analysis of after cetuximab refractory.
Authors: Kobayashi Yoshimitsu , Fukushima Hiraku , Sasaki Takahide , Yuki Satoshi , Okuda Hiroyuki , Kusumi Takaya , Doi Ayako , Tsuji Yasushi , Hatanaka Kazuteru , Uebayashi Minoru , Koike Masahiko , Kato Takashi , Nakamura Michio , Sato Yasushi , Ohta Tomoyuki , Kudo Mineo , Konno Jun , Iwai Kazuhiro , Sakata Yuh , Komatsu Yoshito ,   Hokkaido Gastrointestinal Cancer Study Group
Published: February 2017

541

Background: In the previous studies, panitumumab (Pmab) has been demonstrated the efficacy for patients with metastatic colorectal cancer (mCRC) in all treatment lines. It is still controversial about the efficacy of Pmab for patients that had progressed on prior cetuximab (Cmab), though there had been a few reports (from Metges et al. and Wadlow et al.) regarding the efficacy of Pmab after Cmab refractory or intolerance. To evaluate the efficacy and safety of Pmab in patients with cetuximab-refractory mCRC, in comparison with anti-EGFR antibody naïve patients (Cmab-naïve) and Cmab-refractory or intolerance patients (prior-Cmab). Methods: Two hundred patients with mCRC treated by Pmab contained chemotherapy were retrospectively registered from 20 centers in Japan (HGCSG 1002 study). Of these, the patients that were refractory to or intolerant for 5-FU/ irinotecan/ oxaliplatin, and were administered Pmab monotherapy were included in this analysis. Results: Of 93 patients (44 prior-Cmab and 49 Cmab-naïve) were evaluated. There were no significant differences in the baseline characteristics of the patients in each group. The incidence of Grade 3 or higher any skin toxicities were higher in the Cmab-naïve (26.5.%) than in the prior-Cmab (11.4%). The overall response rate (RR) was not significantly difference (prior-Cmab/ Cmab-naïve, 9.1%/ 10.2%), but the disease control rate (DCR) was slightly higher in Cmab-naïve group (38.6%/ 55.1%, p=0.15). Progression free survival (PFS) and overall survival (OS) were follows: prior-Cmab/ Cmab-naïve, 2.8m/ 3.1m, 6.8m / 9.5m. There was a significant difference between the two groups in OS curve (p=0.04). Conclusions: Pmab was safely administered to heavily pretreated mCRC patients in daily practice. Although there were no significant differences in RR, DCS and PFS between prior-Cmab and Cmab-naïve, but the median OS was longer for the Cmab-naïve group compared with the prior-Cmab group. Therapeutic efficacies of Pmab for prior-Cmab patients did not comparable to those for Cmab-naïve patients. We are now performing a phase II trial on the efficacy of Pmab for Cmab-refractory mCRC patients.
Pathologic tumor and normal mucosa responses after hyperfractionated versus hypofractionated preoperative radiotherapy for rectal cancer.
Authors: Suwinski Rafal , Stobiecka Ewa , Chmielik Ewa , Kryj Mariusz , Chmielarz Andrzej , Widel Maciej , Idasiak Adam , Bialas Marcin , Wydmanski Jerzy , Wzietek Iwona
Published: February 2017

556

Background: The aim of the study is to assess radiation-induced tumor and normal mucosa responses in patients who underwent preoperative radiotherapy according to two different fractionation protocols. This research constitutes one of the secondary endpoints of a prospective randomized trial. Methods: Pathological samples after preoperative radiotherapy and surgery were obtained from 106 patients: 50 were treated with hypofractionation 39 Gy in 3.0 Gy per fraction (HYPO) and 56 with accelerated hyperfractionation 42 Gy given in two daily fractions of 1.5 Gy with a minimal interfraction interval of 6 hours (HART). This sample represents approximately 30% of an overall trial size. Over 50 pathological features were assessed for each sample including tumor/nodal response, normal mucosa and cellular matrix response, ulceration and morphology of tumor cells. The observed grades of responses in HYPO vs. HART were compared using U Mann-Whitney test. Results: The primary tumor downstaging was observed in 41% vs. 35% of the patients treated with HYPO and HART respectively, the difference was not significant (p=0.5). By contrast, a trend towards improved nodal response among the patients treated with HYPO was recorded, with 94% achieving complete or major nodal response, compared to 73% in HART (p=0.03). Mucosal atrophy and edema were significantly higher in HYPO (p=0.003 and p=0.02, respectively). A trend for increased mucosal inflammation was also recorded in HYPO (p=0.06). Tumor/nodal responses were not significantly influenced by time-interval radiotherapy-surgery (below or above the median of 11 days), however, more cellular injury to normal mucosa (atrophy, ulceration) was observed at short RT-surgery intervals (p=0.01). Conclusions: Radiation-induced tumor and normal mucosa responses differ significantly according to fractionation schedule, with more mucosa injury observed in HYPO. Pathological responses of mucosa are also influenced by time-interval radiotherapy-surgery.
Octreotide prescribing patterns in the palliation of symptomatic inoperable malignant bowel obstruction patients at a single U.S. academic hospital.
Authors: Roeland Eric , Hwang Michael
Published: February 2017

563

Background: Medical management is the cornerstone of malignant bowel obstruction (MBO) therapy and includes antisecretory agents such as octreotide. Currently, little data exist regarding octreotide prescribing patterns in U.S. academic hospitals in the palliation of inoperable MBO. Methods: This retrospective chart review evaluated inpatient with inoperable MBO receiving octretodie at a single academic US hospital (2008-2011). The prescribing primary service (medical vs. surgical), days to initiation of octreotide, daily dose, cumulative dose, length of stay (LOS), and overall survival (OS) were analyzed. Multiple linear regression was used to assess if the association between dose and LOS was significant. Kaplan-Meier curves and log rank test were used to evaluate OS. Results: A total of 767 patients received octreotide. 134 had diagnosis of cancer, and 37 (24 female, 13 male; mean age 56.7 years) had a confirmed inoperable MBO. The mean LOS was equivalent on both services (17 days). The mean octreotide dose was 201.2-μg medical vs. 119-μg surgical. Mean time to initiation was 8.4 days (7.9 medical vs. 8.8 surgical). Earlier initiation was associated with a shorter LOS (Spearman’s correlation= 0.76, p<0.0001). No statistically significant association was demonstrated between OS octreotide dose. Conclusions: Early initiation of octreotide may lead to shorter LOS; the association remains after adjustment for patient age. Timing and dose of octreotide use was not significantly associated with survival.
Correlation of bone marrow micrometastases (BMM) with nodal status in gastrointestinal tumors (GI).
Authors: Saha Sukamal , Korant Alpesh , Krishnamoorthy Madhumitha , Kanaan Mohammed Nawaf , Abadeer Benjamin , Arora Madan L. , Singh T. Trevor , Nagpal Sunil , Wiese David
Published: February 2017

567

Background: Presence of BMM is an important prognostic factor for patients (pts) with solid tumors. Sentinel lymph node (SLN) mapping (M) has been found to upstage pts with GI tumors. However, a direct correlation between the presence of BMM and nodal metastases is lacking. Hence, a retrospective study was undertaken to determine the relationship between BMM and nodal status in GI tumors. Methods: A total of 385 consecutive pts with GI tumors were analyzed. All pts underwent bilateral posterior superior iliac spine BM aspiration. This protocol employs highly sensitive staining methods combined with automated microscopy to differentiate cytokeratin +ve cells of epithelial origin from normal hematopoetic cells in BM. The cytospin slides were stained with the monoclonal anti-CAM 5.2 antibody from Becton Dickinson at a 1:25 dilution. Visualization was achieved with Ventana view Red detection system. The slides were counterstained with Ventana haematoxylin. The Automated Cellular Imaging System is applied to detect, count, and classify cells of clinical interest based upon the recognition of cellular objects of particular color, size and shape. SLNM when applicable was done by peritumoral injection of 1% methylene blue. Results: Of these 385 pts, 11.2% were found to have BMM. When analyzed by sites, the 3 highest BMM were Cholangiocarcinoma 33%, Stomach 22% and esophagus 13%. The BMM was +ve bilaterally in 44%; unilaterally in 56%. In pts who underwent SLNM, BMM were found in 8.3% of SLN +ve vs. 12% for SLN -ve pts. For pts with colon cancer undergoing SLNM, BMM were found in 9.6% of SLN +ve pts vs. 11.1% for SLN -ve pts. Conclusions: BMM did not correlate with nodal status for GI malignancies suggesting a possible different mechanism for metastases. Detection of BMM may have a significant clinical value in SLN negative pts who may benefit from adjuvant therapy. [Table: see text]
Evaluation of the pathologic features of positive lymph nodes in the mesorectum after short-term preoperative chemoradiotherapy.
Authors: Beppu Naohito , Yanagi Hidenori , Doi Hiroshi , Kamikonya Norihiko , Inoue Yasuhiro , Tomita Naohiro , Yamanaka Naoki
Published: February 2017

571

Background: The purpose of this study was to investigate the relationship between the pathological degeneration of primary tumor and positive lymph nodes (LNs) after preoperative chemoradiotherapy for rectal cancer. Methods: We analyzed the resected specimens from 53 patients (pts) with ypN+ rectal cancer received curative resection after chemoradiotherapy (25 Gy/10 fr/5 days+S-1 80 mg/m2×10 days).The primary tumor regression was assessed using the tumor regression grade (TRG 0 to 4) according to Dworak classification. 144 positive LNs in the mesorectum were measured and were assessed using the LN regression grade (LRG) as follows; LRG 1 =minor to moderate regression, LRG 2 =major regression, and LRG 3 =total regression. To confirm apoptosis, the LNs with LRG 2 or 3 were stained by TUNEL method. Furthermore, we examined the relationship among the size of LNs, the TRG, and the LRG. Results: The TRG 1, 2, and 3 was found in 24 pts, 15 pts, and 14 pts, respectively. In addition, there were no pts with TRG 0 or 4. The LRG 1, 2, and 3 was found in 74 LNs, 48 LNs, and 22 LNs, respectively. 14 in 15 LNs equal to or greater than 10 mm (≥10mm) showed the LRG 1.Whereas, in 129 LNs less than 10 mm (<10mm), the proportion of the LRG 2 or 3 in pts with each TRG was 33.8 % (26/77), 69.0 % (20/29), and 100 % (23/23) in the TRG 1, 2, and 3 respectively. Conclusions: 1) Larger LNs (≥10 mm) seemed to be radioresistant. 2) A good correlation of the response to chemoradiation between the primary tumor and LNs were observed in smaller LNs (< 10 mm). 3) Primary tumor with the TRG 3 can predict the efficacy of preoperative chemoradiotherapy for the positive LNs in the pts with rectal cancer.