bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survivorship after lower gastrointestinal cancer: Patient reported outcomes and planning for care.
Authors: Frick Melissa , Vachani Carolyn , Hampshire Margaret K. , Bach Christina , Arnold-Korzeniowski Karen , Metz James M. , Hill-Kayser Christine E. 
Published: March 2017

695 Background: There is significant need for quality follow-up care to optimize long-term outcomes for the growing population of lower gastrointestinal (GI) cancer survivors. Patient-reported outcomes (PROs) provide valuable information regarding late- and long-term effects. Methods: Using a convenience sample from 1,129 colon, rectal and anal cancer survivors (n=792, 218, and 119, respectively) who utilized an Internet-based survivorship care plan (SCP) tool, we examined patient-reported demographics, treatment, and toxicity data. Responses from a follow-up survey were reviewed. Results: Median age of diagnosis was 51 years and median current age was 54 years. 81% of respondents were Caucasian and 58% were female. The most commonly reported late- and long-term effects for all survivors were neuropathy (65%), fatigue (56%), cognitive changes (49%), changes in GI function (43%), sexual dysfunction (22% in males, 43% in females), and radiation-induced dermatologic effects including changes in color/texture of skin (39%) and loss of flexibility in radiated areas (31%). The prevalence of these effects varied with length of time since treatment and treatment modality. Anal cancer patients reported a high prevalence of sexual dysfunction and radiation-induced dermatologic effects. Over 87% of users reported satisfaction levels of "good" to "excellent" using this tool, and 69% reported they intend to share SCP with their healthcare team. Conclusions: For lower GI cancer survivors, it is feasible to obtain PROs from an Internet-based survivorship tool. Survivors report a wide spectrum of late- and long-term side effects, which can be used to inform counseling at time of diagnosis, as well as help anticipate and respond to disease- and treatment-related sequelae during follow-up. We are among the first to report on PROs in anal cancer survivors. Further investigation on the impact of SCPs on healthcare communication and use is needed.
Predictive value of PET/CT for pathological complete response and survival in patients with locally advanced rectal cancer.
Authors: Sorenson Eric C , Choudhry Aruj J , Yu Jian Qin , Reddy Sanjay S. , Denlinger Crystal Shereen , Meyer Joshua E. , Farma Jeffrey M. , Sigurdson Elin R. 
Published: March 2017

697 Background: A major challenge in identifying candidates for nonoperative management of locally advanced rectal cancer is predicting pathological complete response (pCR) following chemoradiation therapy (CRT). We evaluated the ability of pre- and post-CRT PET imaging to predict pCR and long-term prognosis. Methods: We retrospectively identified patients at our institution from 2002–2015 with locally advanced rectal cancer who underwent CRT, pre- and post-CRT PET imaging, and surgical resection. Logistic regression and Kaplan-Meier estimates were used to analyze the association of PET variables with tumor pCR and survival outcomes. Receiver operator characteristic curves were generated to define optimal cutoff points for predictive PET variables. Results: 140 patients matched the inclusion criteria. The pCR rate was 28%, and median follow-up time was 48 months. On multivariable analysis, pCR was associated with lower median post-CRT SUVmax(3.2 vs 5.2, p=0.009) and higher median SUV percent decrease (72 vs 58%, p=0.009). ROC curves were generated for SUV percent decrease (AUC=0.70) and post-CRT SUV (AUC=0.69) to estimate cutoff points for maximum specificity and sensitivity to predict pCR. Post-CRT SUV <4.3 and SUV percent decrease of >66% were equally predictive of pCR with a sensitivity of 65%, specificity of 72%, PPV of 44%, and NPV of 86%. Median 5-year OS and RFS were significantly improved for patients with post-CRT SUV <4.3 (OS, 86 vs 66%, p=0.01; RFS, 75 vs 52%, p=0.01) or SUV percent decrease of >66% (OS, 82 vs 66%, p=0.05; RFS, 75 vs 54%, p=0.01). Patients with stage III disease and a post-CRT SUV <4.3 were in effect downstaged, with a median 5-year OS equivalent to that of patients with stage II disease (Table 1; 86 vs 86%). Conclusions: PET/CT may be a useful modality in predicting pCR and overall survival in patients undergoing CRT for rectal cancer. Inclusion of pre-CRT PET does not appear to add prognostic value for pCR compared with post-CRT PET alone. Patients with a post-CRT SUV of >4.3 should not be considered for nonoperative management, as an estimated 86% of these patients will not have a pCR.
Cetuximab (Cet) clearance and survival in patients (pts) with metastatic colorectal cancer (mCRC).
Authors: Jiang Di Maria , Sim Hao-Wen , Siu Lillian L. , Shapiro Jeremy David , Liu Geoffrey , Price Timothy Jay , Jonker Derek J. , Karapetis Christos Stelios , Strickland Andrew , Zhang Wenjiang , Jeffery Mark , Tu Dongsheng , Ng Siobhan , Sabesan Sabe S. , Shannon Jenny , Townsend Amanda Rose , Morgen Eric , Xu Wei , O'Callaghan Christopher J. , Chen Eric Xueyu 
Published: March 2017

699 Background: Cet, a monoclonal antibody against EGFR, is a standard therapy for pts with RAS wild-type (WT) mCRC. Limited previous data suggest that Cet clearance correlates with progression-free survival (PFS). We performed a population pharmacokinetic (pop-pK) analysis of Cet in pts who participated in the randomized phase III NCIC CO.20 trial in KRAS WT mCRC patients. Methods: Standard Cet doses ± brivanib were administered. Using intermittent trough blood samples, pop-pK analysis was conducted to evaluate different models. Pts were divided into quartiles according to clearance parameters to assess the exposure-response relationship to response rate (RR), PFS and overall survival (OS). Clinical variables including demographic, laboratory, disease characteristics and co-administration of brivanib were evaluated as co-variates on Cet clearance. Results: In 701 pts, Cet elimination was best described as a one-compartment model with a non-linear saturable elimination process (defined by Vmax and Km). Mean values (± standard deviation) for pop-pk parameters were 2.7 ± 0.5 L/m2 for V, 2.5 ± 0.3 mg/h/m2 for Vmax, and 101.0 ± 0.05 mg/L/m2 for Km. Grouped into quartiles, Vmax and Km were significantly associated with OS, but not RR or PFS. The median OS for pts in the lowest quartile of Vmax was 12.0 ms versus (vs.) 6.9 ms for pts in the highest quartile ( p< 0.001), while the median OS was 11.6 ms in the highest Km quartile vs. 6.9 ms in the lowest Km quartile ( p< 0.001). When compared to the quartile with the combination of highest Vmax and lowest Km, pts in the quartile with the lowest Vmax and highest Km had longer PFS (5.0 vs. 3.7 ms, HR 0.75 (95% confidence interval (CI) 0.58-0.98, p= 0.032) and OS (11.7 vs. 6.6 ms, HR 0.59 (95% CI, 0.45-0.77, p< 0.001). Pts in the lower Vmax and higher Km quartiles also experienced less grade 3 toxicity. Neither clinical variables nor brivanib administration were associated with Cet clearance parameters. Conclusions: For KRAS WT mCRC, standard Cet dosing is not optimal for all pts. Pts with slower Cet clearance have significantly improved PFS and OS. Further studies are needed to optimize Cet doses based on individual pK assessments, and to identify novel factors associated with clearance.
Using NSG recipient mice improves engraftment of gastric cancer patient derived xenografts.
Authors: Wang Sam C. , Zhu Min , Nassour Ibrahim , Shen Jeanne , Mansour John C. , Agarwal Deepak , Zhu Hao , Porembka Matthew R. 
Published: March 2017

70 Background: Previous gastric cancer (GC) patient derived xenograft (PDX) studies reported engraftment rates inversely proportional to the immunocompromised states of recipient mice (nudes 17%, scid 27%, and NOD/ scid 34%). We tested highly immunocompromised NOD scidgamma (NSG) mice, which lack mature T cells, B cells, or functional natural killer cells, as recipients for low volume biopsies and post-treatment GC samples. Methods: Consent was obtained from GC patients who were scheduled to undergo esophagogastroduodenoscopy (EGD) and diagnostic laparoscopy as part of their disease management strategies. The following amounts of tumor were coated with Matrigel and inoculated into the flanks of NSG mice: EGD biopsies ~10 mg, post-treatment samples ~100 mm3, and peritoneal metastasis biopsies ~100 mm3. Tumors were serially measured and passaged when the greatest dimension reached 1.5 cm, or if there was overlying skin necrosis. Results: The engraftment rates were: EGD biopsies 48% (13 of 27 samples), post-resection samples 58% (7 of 12), and peritoneal metastases 11% (1 of 9). Median time to first passage was 10.1 weeks (range: 8.1 to 12.4) for EGD biopsies and 22.1 weeks (9.6 to 33.0) for post-treatment samples. Two (15%) engrafted EGD mice developed liver metastases, and one (7.7%) had axillary lymph node metastasis (AxLN). Three (47%) engrafted post-treatment mice had liver metastases and two (29%) had AxLN. Histology was generally maintained through passages and metastases with some loss of mucinous components. There were no associations between engraftment rate and any evaluated clinical or pathologic characteristics, including tumor response and overall survival. The tumor from the one patient who had a complete pathologic response after NAT did not engraft. Conclusions: Using highly immunocompromised NSG mice improved engraftment rates of GC PDX, even for challenging specimens such as endoscopic biopsies and post-treatment resection samples. Peritoneal biopsies did not engraft well. Tumor histology was generally maintained through passages. Studies comparing the expression profiles of serially passaged tumors to the original clinical samples are ongoing.
Systemic chemotherapy (CT) as salvage treatment for locally advanced rectal cancer (LARC) patients (pts) who fail to respond to neoadjuvant chemoradiotherapy (CRT).
Authors: Sclafani Francesco , Brown Gina , Cunningham David , Rao Sheela , Tekkis Paris P , Tait Diana M. , Morano Federica , Baratelli Chiara , Kalaitzaki Eleftheria , Rasheed Shahnawaz , Watkins David J. , Starling Naureen , Wotherspoon Andrew , Chau Ian 
Published: March 2017

709 Background: International guidelines suggest that RT dose escalation, intraoperative RT or brachytherapy could be considered for LARC pts with positive resection margins, pT4 or unresectable tumours after standard neoadjuvant CRT. However, data to support these approaches are scarce. The potential of systemic CT as salvage treatment after failure of neoadjuvant CRT for LARC has never been explored. We conducted a single-centre, retrospective analysis to address this question. Methods: Pts with newly diagnosed rectal adenocarcinoma who were deemed inoperable or candidates for extensive (i.e. beyond total mesorectal excision, TME) surgery after completion of long-course RT and received salvage systemic CT were included. The primary objective was to estimate the proportion of pts who became potentially suitable for TME after CT. Secondary objectives included the proportion of pts who ultimately underwent TME and survival outcomes. Results: 45 pts (2001-2015) met the study inclusion criteria (39 candidates for extensive surgery and 6 with unresectable tumours). Previous RT was given concurrently with CT in 43 cases (median dose: 54.0 Gy; range: 34.0-55.8). Salvage oxaliplatin-based and irinotecan-based CT was administered in 40 (88.9%) and 5 (11.1%) cases, respectively. 8 pts (17.8%) became suitable for TME based on the MRI after CT, 10 (22.2%) ultimately underwent TME with clear margins and 2 (4.4%) were managed with a watch & wait approach following radiological clinical complete response. Additionally, 13 pts had a beyond-TME surgery with curative intent. 3-year progression-free survival and 5-year overall survival in the entire population were 30.0% (95% CI: 15.0-46.0) and 44.0% (95% CI: 26.0-61.0), respectively. For the curatively resected and watch & wait pts these figures were 52.0% (95% CI: 27.0-73.0) and 67.0% (95% CI: 40.0-84.0), respectively. Conclusions: Systemic CT may be an effective salvage strategy for LARC pts who fail to respond to long-course CRT and are inoperable or candidates for beyond-TME surgery. According to our study, 1 out of 4 pts may become resectable or being spared from an extensive surgery after systemic CT.
Primary tumor location as a prognostic and predictive factor in metastatic colorectal cancer (mCRC) treated with chemotherapy plus cetuximab: A retrospective analysis.
Authors: Sagawa Tamotsu , Hamaguchi Kyoko , Sakurada Akira , Tamura Fumito , Hayashi Tsuyoshi , Fujikawa Koshi , Takahashi Yasuo , Sato Yasushi 
Published: March 2017

711 Background: Left- and right-sided colon cancers are significantly different in epidemiologic, clinicopathological and molecular characteristics. However, the impact of primary tumor location in mCRC treated biological targeted agent in combination with chemotherapy is unclear. We therefore investigated the prognostic and predictive impact of primary tumor location in mCRC. Methods: Single-institution, retrospective, case-control study was reviewed. A total of 96 patients with mCRC were enrolled between January 2011 and December 2015. We evaluated the association between tumor location and survival parameters in patients with previously untreated mCRC receiving first-line chemotherapy plus cetuximab or bevacizumab. The impact of primary tumor location for cetuximab and bevacizumab groups was analyzed, respectively. Left-sided primary tumors were defined as tumors from rectum to splenic flexure, while right-sided primary tumors were defined as tumors from cecum to the distal part of the transverse colon. Results: 68 patients presented left-sided tumors and 28 patients right-sided primary tumors. In the cetuximab group, left-sided tumors were significantly superior to right-sided tumors in terms of the progression-free survival (PFS) and Overall survival (OS) (PFS, left vs right, 18.3 vs 6.8 M, p = 0.0415; OS, 50.6 vs10.5 M, p = 0.0004). Likewise, in the bevacizumab group, OS showed differences between the left- and right-sided tumors (PFS, left vs right, 11.6 vs 7.3 M, p = 0.1904; OS, 25.7 vs 16.2 M, p = 0.0389). In left-sided tumors, cetuximab group were significantly superior to bevacizumab group in terms of the OS (PFS, cetuximab vs bevacizumab, 18.0 vs 11.6 M, p = 0.1088; OS, 50.6 vs 25.7 m p = 0.0354). Conversely, in right-sided, the survival times showed no differences between cetuximab- and bevacizumab group (PFS, cetuximab vs bevacizumab, 6.8 vs 7.3 M, p = 0.7816; OS, 10.5 vs 16.2 M, p = 0.1088). Conclusions: Our study demonstrates that primary tumor location is an important prognostic factor in previously untreated mCRC. Furthermore, left-sided primary tumor location might be a strong predictor of PFS and OS in cetuximab therapy.
Effect of number of prior lines versus prior regimens in pts receiving trifluridine/tipiracil (TAS-102).
Authors: Van Cutsem Eric , Ohtsu Atsushi , Leger Catherine , Amellal Nadia , Poirot Camille , Fougeray Ronan , Mayer Robert J. 
Published: March 2017

720 Background: RECOURSE showed that treatment with trifluridine/tipiracil in patients (pts) with refractory metastatic colorectal cancer was associated with significantly improved overall survival (OS) versus placebo. Pts were classified in this analysis according to number of prior regimens of anticancer therapy, i.e. regardless of treatment duration or occurrence of progressive disease (PD). Classification by prior lines of treatment may provide a better appreciation of prognosis than prior regimens. Methods: We performed a post hoc analysis of the RECOURSE population to explore the effect of number of prior lines of treatment vs prior regimens on OS in metastatic disease. We analysed individual pt data (n = 800) and reclassified pts on the basis of prior lines of treatment (< 3, 3, and > 3). In our analysis, a line of treatment ended with clinical or radiological PD. Adjuvant treatments counted as a line if the pt had had PD within 6 months after the end of treatment. If there was a delay > 6 months between 2 regimens, they could still count as 1 line. Treatments stopped due to toxicity were not considered as a line (since they were not stopped due to PD). Results: When the RECOURSE population was divided by prior lines, there were 170/83 trifluridine-tipiracil/placebo pts receiving < 3 lines of treatment, 174/72 receiving 3 lines, and 190/111 receiving > 3 lines. By contrast, there were 95/45 pts receiving < 3 regimens, 119/54 receiving 3 regimens, and 320/167 receiving > 3 regimens. Conclusions: Clinically, it appears that patients with 1 or 2 prior lines of anticancer therapy (with PD between lines) are different from patients with 1 or 2 prior regimens (which may have been within the same line of treatment). Analyzing the RECOURSE results according to prior lines of treatment provides a more homogeneous classification than prior regimens (smaller CIs) with lower HRs for OS. Clinical trial information: NCT01607957. [Table: see text]
A phase II study of panitumumab with FOLFOX or FOLFIRI as first-line chemotherapy for KRAS-wild type metastatic colorectal cancer: The PaFF-J study.
Authors: Shinozaki Eiji , Ishiguro Megumi , Nakatani Eiji , Yamaguchi Tatsuro , Nakamura Masato , Miyamoto Yuji , Ojima Hitoshi , Honma Yoshitaka , Gotoh Masahiro , Ishikawa Toshiaki , Takahashi Keiichi , Shimada Yasuhiro , Yoshida Kazuhiro , Mizunuma Nobuyuki , Muro Kei , Komatsu Yoshito , Yamaguchi Kensei , Nakano Hiroshi , Koike Junki , Sugihara Kenichi ,   PaFF-J Study Group
Published: March 2017

722 Background: For the patients with unresectable metastatic colorectal cancer (mCRC), response to the1st line chemotherapy has strong impact on their prognosis. Shrinkage of tumors may result in conversion to surgical resection and, concurrently, improved their survival. We conducted a multicenter phase II trial to investigate the efficacy and safety of panitumumab (Pmab) with chemotherapy as the 1st line treatment in Japanese patients with mCRC. Methods: Patients with no prior chemotherapy for unresectable, KRAS wild type mCRC, 20-80 years, and PS 0-1 were arbitrarily received either FOLFOX + Pmab or FOLFIRI + Pmab. Patients were evaluated every 8 weeks until progression. The primary endpoint was overall response rate (ORR), the secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), R0 resection rate, and safety. Results: A total of 162 patients (140 with FOLFOX + Pmab and 22 with FOLFIRI + Pmab) were analyzed. Median follow-up was 28.2 months, median age at enrollment was 64.5 years, and 17.9% of the patients was recurrent disease. Number of target organ was 1 in 35.2%, 2 in 40.7%, and ≥ 3 in 24.1% of the subjects. Median administered cycle was 7, and median treatment duration was 16 weeks. ORR was 51.2% (95%CI: 43.3-59.2), and DCR was 82.1% (95%CI: 75.3-87.7). ≥ 30% tumor shrinkage (PR-in) was observed in 115 patients (71.0%). Median time to PR-in and maximum shrinkage was 10 and 16 weeks, respectively. Surgical resection was done in 66 patients (40.7%), of which R0 was in 43 patients; R0 resection rate was 26.5% (95%CI: 19.9-34.0). Median PFS and OS was 9.2 (95%CI: 7.2-11.4) and 33.8 months (95%CI: 29.4-43.1), respectively. ≥ Grade 3 adverse events with > 5% incidence were neutropenia (31.8%), stomatitis (10.5%), rash acneiform (9.9%), paronychia (9.3%), anorexia (8.6%), and diarrhea (6.2%). Conclusions: In our study, OS was favorable with high R0 resection rate, whereas ORR, DCR, PFS and toxicities were similar to those in previously reported studies. Because the maximum tumor shrinkage was observed around 16 weeks, optimal timing for considering conversion surgery might be 16 weeks from the start of treatment. Clinical trial information: UMIN000004991.
Representation of peritoneal metastases in published clinical trials of metastatic colorectal cancer.
Authors: Tseng Jennifer , Bryan Darren S , Poli Elizabeth , Sharma Manish , Polite Blase N. , Turaga Kiran 
Published: March 2017

725 Background: Peritoneal metastases occur in 6-15% of patients with metastatic colorectal cancer. Non-invasive detection of peritoneal metastases is difficult given limitations in discrimination of cross sectional imaging. We hypothesized that patients with peritoneal metastases are underrepresented in clinical trials. Methods: Randomized controlled trials of systemic chemotherapy for metastatic colorectal cancer between 2003-16 were included after a PubMed search. Articles were restricted to those published in leading oncology journals and with ≥100 patients (total). Protocol designs were hand searched to identify whether clinical trials explicitly included or reported on patients with peritoneal metastases. Results: Of 72 clinical trials identified, 7 (10%) studies specifically reported inclusion of peritoneal disease (Table 1). Of 45,783 patients enrolled in all trials, 670 patients (1.5%) specifically had peritoneal metastases. Response for peritoneal disease was measured using Response Evaluation Criteria in Solid Tumors (RECIST) criteria in 6 (of 7, 86%) and modified World Health Organization (WHO) criteria in 1 but not reported in the final manuscript or supplementary material. Peritoneal specific outcomes were not reported in any study. No studies included metastatic colorectal cancer patients with peritoneal metastases alone. Conclusions: Patients with peritoneal metastases are underrepresented in published clinical trials. Specific efforts to include patients, measure burden of disease and response to therapy and report peritoneal specific outcomes are essential to draw generalizable inferences. [Table: see text]
Utilization of primary chemoradiotherapy for anal squamous cell carcinoma in the elderly: An analysis of the NCDB.
Authors: Motz Benjamin Mitchell , Lorimer Patrick Daniel , Walsh Kendall K , Perry I'sis N , Boselli Danielle , White Richard L. , Salo Jonathan C. , Hill Joshua S. 
Published: March 2017

726 Background: Definitive chemoradiotherapy (CHEMORT) is the treatment of choice for anal squamous cell carcinoma (SCC), while surgery is typically reserved for salvage therapy. Patients (pts) who are frail due to advanced age or medical comorbidities often have difficulty completing therapy. Methods: The NCDB was queried for pts with anal SCC (2004-2012). Pts < 50 years, and those with in situ or metastatic disease, or with incomplete CHEMORT treatment data were excluded. The primary outcome was completion of CHEMORT. Secondary outcome was requirement of salvage surgical therapy. Statistical analyses include Chi-square, univariate and multivariable logistic regression. Results: N = 11918. 5907 (49.5%) did not complete recommended CHEMORT. 9862 (82.8%) received CHEMO, 6011 (61.0%) of whom completed RT with dosage > 45Gy. Factors significantly associated with failure to complete therapy on multivariable analysis include: older age at diagnosis, higher Charlson-Deyo score, earlier year of diagnosis, male gender, and earlier clinical T and N stages (Table 1). 41.7% of pts who did not complete CHEMORT required salvage surgical therapy, versus 25.1% of pts completing CHEMORT (OR: 2.14 95% CI [1.97, 2.31], p < 0.01). Conclusions: Approximately half of pts older than 50 years of age with anal SCC failed to complete definitive CHEMORT. This study highlights the negative impact of frailty on the ability of pts to receive optimal therapy, resulting in more operative interventions. Medical optimization of older pts with more comorbidities in order to improve utilization of CHEMORT is one possible area of improvement in the management of anal SCC. [Table: see text]