bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of adjuvant therapy use and survival outcomes in patients with rectal cancer not receiving neoadjuvant therapy in an Australian cohort.
Authors: Wilkinson Kate Jessica , Kang Sharlyn , Lim Stephanie Hui-Su , Lee Cheok Soon , Asghari Ray , Chua Wei , Ng Weng Leong , Mandaliya Hiren A. , Maloney Sarah , Chen James , Nasser Elias H. , Brungs Daniel 
Published: January 2019

675 Background: Consensus international guidelines recommend the use of neoadjuvant chemo-radiotherapy in patients with stage II-III rectal cancer. Despite this, due to factors including inaccurate/under-staging, patient co-morbidities and acute presentations, a proportion will undergo up-front surgical resection. The survival benefit of adjuvant therapy is unclear in this real world, non-trial population. Methods: A retrospective analysis of patients presenting with stage II-III rectal adenocarcinoma in South Western Sydney and Illawarra Shoalhaven Health Districts, Australia, between 2006 to 2015 was performed. Data was extracted from electronic health records, with institutional ethics approval. Treatment modalities, clinicopathological, recurrence and survival data were analyzed. The primary endpoint was overall survival (OS) by treatment modality. Results: 549 patients were identified, of which 295 (54%) underwent up-front surgical resection without neoadjuvant therapy. Of this cohort, 137 (46%) had no adjuvant therapy (Group A), 103 (35%) had adjuvant chemotherapy alone (Group B), and 55 (19%) had adjuvant radiotherapy +/- chemotherapy (Group C). Receipt of any adjuvant treatment was significantly associated with improved OS (5 year OS 56 vs. 79%, HR 0.44, 95% CI 0.3 – 0.6, p < 0.0001) and recurrence free survival (5 yr RFS 25% vs. 47%, HR 0.66, 95% CI 0.5 – 0.9, p=0.01), but not cancer specific survival (5yr CSS 75 vs. 80%, HR 0.78, 95% CI 0.5 – 1.3, p = 0.30). Group B had improved OS compared to Group A (5 yr OS 56% vs. 80%, HR 0.35, 95% CI 0.22 – 0.55, p < 0.0001). There was a trend to improved OS in Group C vs. Group A (5yr OS 56.0% vs. 69.2%, HR 0.79 95% CI 0.6 – 1.01, p = 0.052). The improved OS in Group B versus Group A remained significant in multivariate analysis (HR 0.41, 95% CI 0.22 – 0.77, p = 0.005). Conclusions: Adjuvant chemotherapy improved OS in this real world cohort, and there was a trend to a benefit with adjuvant chemo-radiotherapy. However, the lack of difference in cancer specific survival suggests that this benefit may be partly driven by patient selection bias. Further exploratory analyses to identify sub-groups deriving a cancer specific survival benefit are required.
Rectal cancer treatment and outcomes in elderly patients treated with curative intent.
Authors: Kang Sharlyn , Wilkinson Kate Jessica , Brungs Daniel , Chua Wei , Ng Weng Leong , Asghari Ray , Chen James , Nasser Elias H. , Mandaliya Hiren A. , Maloney Sarah , Winn Robert , Putnis Soni , Lee Cheok Soon , Lim Stephanie Hui-Su 
Published: January 2019

678 Background: There is limited information on outcomes in elderly patients with rectal cancer as they are often excluded from clinical trials. This study aimed to assess treatment patterns and outcomes in these patients. Methods: We utilised data from electronic records to identify patients aged ≥ 70 years with a histological diagnosis of rectal cancer from 2006-2015, treated in the South Western Sydney and Illawarra Shoalhaven Local Health Districts, Australia. Treatment modalities, recurrence and survival data were analysed. Results: We identified 942 patients with rectal cancer, with median follow-up of 3.4 years. 393 patients (42%) were aged ≥ 70 years. Median age of this cohort was 77 years (range 70–96 years). Elderly patients were more likely to present with locoregional disease (stage I-III, 83% vs. 75%) and more likely to receive palliative treatment only (21% vs. 16%, p = 0.0005). Of 704 patients who received treatment with curative intent, 300 (43%) were ≥ 70 years. Although clinicopathological features were similar between elderly and young patients, patients ≥ 70 years were more likely to be treated with surgery alone (56% vs. 28%, p < 0.0001), less likely to receive neoadjuvant (25% vs. 44%, p < 0.0001) or adjuvant treatments (29% vs. 55%, p < 0.0001), or be discussed in a multidisciplinary meeting (51% vs. 61%, p = 0.001). Compared to younger patients, elderly patients had a significantly poorer overall survival (HR 2.9, 95% CI 2.2 – 3.7, p < 0.0001). There were no significant differences in cancer specific survival (HR 1.4, 95% CI 0.98 – 2.0, p = 0.06) or relapse free survival (HR 0.92, 95% CI 0.7 – 1.2, p = 0.60). Conclusions: Although more elderly patients were treated with palliative intent compared to younger patients, the majority of elderly rectal cancer patients were still treated with curative intent. Most had surgery alone. Uptake of neoadjuvant and adjuvant therapy, as well as multidisciplinary involvement, was lower. Elderly patients had similar cancer-specific outcomes compared to younger patients, supporting curative intent treatment in these patients. Further analyses are underway to identify subgroups in the elderly population who benefit from trimodality therapy, and potential differences in their disease biology.
Sequencing of different targeted therapies in management of KRAS wild-type metastatic colorectal cancer: A meta-analysis.
Authors: Li Jin , Chen Gong , Fang Weijia , Tang Yongsong 
Published: January 2019

679 Background: First-line (1L) antiendothelial growth factor receptor (anti-EGFR) is considered suitable in metastatic colorectal cancer (mCRC) patients. As no treatment guidelines recommend target therapy sequence in mCRC, this meta-analysis determined the optimal sequence of targeted therapies in patients with KRAS wild type (WT) mCRC. Methods: PICO framework was used to retrieve relevant studies from PubMed, Embase, Cochrane Library and Google Scholar. mCRC patients treated with 1L anti-EGFR and second-line (2L) anti -VEGF were compared with 1L anti-VEGF and 2L anti-EGFR treatment (gp. A). Patients treated with 1L anti-VEGF and 2L anti-EGFR treatment were compared with anti-VEGF in 1L and 2L (gp. B). We also compared 2L and 3L anti-EGFR therapies (gp. C). Primary and secondary outcomes of overall survival (OS) and progression free survival (PFS) were presented as hazard ratio (HR) and 95% confidence intervals (95% CIs). Objective response rate (ORR) was evaluated in terms of relative risk (RR) and 95% CI. P < 0.05 was considered statistically significant. Results: We identified nine studies for this analysis including 1478 KRAS WT mCRC patients. In gp. p A (three studies; two retrospective and one post-hoc analysis; 450 patients), 1L anti-EGFR and 2L anti-VEGF treatment had a significantly higher OS (HR 0.83, 95% CI 0.53-1.32; p = 0.0022) and PFS (HR 0.85, 95% CI 0.76- 0.96; p = 0.0081) than 1L anti-VEGF and 2L anti-EGFR. Comparison in gp. B (n = 3 RCTs involving 431 mCRC KRAS WT patients) showed no significant difference in OS (HR 0.95, 95% CI 0.70- 1.29; p = 0.6897; I2 = 42.69%) and PFS (HR 1.43, 95% CI 0.83- 2.47; p = 0.1962; I2 = 81.55%) between the two lines of treatment. ORR was higher with anti-VEGF in both 1L and 2L in gp. B (RR 3.58, 95% CI 0.72- 17.85; p = 0.1191). In gp. C, indirect comparison showed similar OS with 3L and 2L anti-EGFR therapies ((3L and 2L: n = 2 studies each; HR 0.86. 95% CI 0.71-1.04; HR 0.78, 95% CI 0.51-1.20; 2L vs. 3L; p = 0.06). Conclusions: Patients with KRAS WT mCRC achieved maximum benefit with 1L anti-EGFR and 2L anti-VEGF than with 1L anti-VEGF and 2L anti-EGFR or 1L and 2L anti-VEGF. Hence, it is suggested to initiate the therapy with 1L anti-EGFR to derive the maximum clinical benefit.
Watch and wait approach following neoadjuvant chemoradiotherapy for rectal cancer patients: A single-centre experience.
Authors: Zhu Ji , Wang Jingwen 
Published: January 2019

681 Background: A watch-and-wait approach for patients with clinical complete response to neoadjuvant chemoradiation could avoid the morbidity of conventional surgery for rectal cancer. Here, we report the survival outcome of patients with this strategy in our center. Methods: We retrospectively analyzed the rectal cancer patients who received neoadjuvant chemoradiotherapy since 2015 in our center. Preoperative regimen included long-course radiotherapy (50 Gy / 25 Fx) combined fluoropyrimidin–based chemotherapy concurrently. MRI and endoscopic evaluation were performed after preoperative treatment. Patients with complete tumor response were referred to the “watch-and-wait” approach and omitted the surgery. Four to six cycles of consolidation chemotherapy were performed. Patients were followed up clinically, endoscopically, and radiologically to assess for local recurrence or disease progression. Results: From January 2015 to March 2018, a total of 47 patients with rectal cancer in our center received conservative treatment following neoadjuvant therapy. The median age of the patients is 58 (53-66). The proportions of stages I to IV are 4.3%, 12.8%, 70.2%, 8.5%, respectively. After a median follow-up of 20 month, tumor regrowth occurred in five out of 47 (10.6%) patients. All local regrowth was diagnosed in the first two years, and four out of five (80%) of local regrowth was located in the bowel wall. All patients underwent salvage surgery. Distant metastasis was diagnosed in four of 47 patients (8.5%). two-year overall survival was 89.9%, and two-year disease-free survival was 76.5%. Conclusions: Organ preservation for locally advanced rectal cancer is feasible for selected patients who achieve a complete response to individualized neoadjuvant CRT. The survival of patients is not impaired with “watch-and-wait” strategy.
Determining optimal follow up for patients with anal cancer following chemoradiation.
Authors: Frazer Marissa , Yang George Q , Felder Seth , Sanchez Julian , Dessureault Sophie , Imanirad Iman , Carballido Estrella M. , Kim Richard D. , Hoffe Sarah E. , Frakes Jessica 
Published: January 2019

689 Background: U.S. health care is increasingly defined by over expenditure and inefficiency. Optimizing patient follow-up is critical especially in cancers treated with high control rates. The objective of this study was to assess time to disease recurrence or toxicity in a cohort of patients with anal carcinoma in order to optimize patient care. Methods: 140 patients diagnosed with biopsy-proven, non-metastatic anal carcinoma, treated with chemoradiation utilizing IMRT, were identified from an institutional database at our high volume center. After IRB approval, a retrospective study was conducted that evaluated local recurrence (LR), distant metastasis (DM), overall survival (OS), and late ≥ grade three toxicity (LG3T) based on National Cancer Institute Common Terminology for Adverse Events version 4. Patients were followed post-treatment every three months for two years, every six months in years 3-5 then yearly thereafter with imaging per National Comprehensive Cancer Network recommendations. Results: Median age and follow up is 58 years and 27 months, respectively. Patients were staged based on AJCC 8th edition and 24 patients were stage I (17%), 55 stage II (39%) and 61 stage III (44%). The median radiation dose was 54 Gy (range: 40-62.5), and 11% of patients required a radiation break. The two year LC, DMFS, and OS were 93%, 94% and 89% and 5-year LC, DMFS, OS were 92%, 87% and 85% respectively. In total, there were 29 disease or treatment related events: LR occurred in nine patients, DM in 11 patients, and LG3T in nine patients. Overall, 62% of events occurred within year one and 77 % within two years. Stratified by event type, at two years 79% of LR, 64% of DM and 89% LG3T were identified. At the remaining follow-up points after 2 years there was an event incidence rate of 1.4%. Conclusions: The majority of recurrences/toxicities in patients diagnosed with non-metastatic anal carcinoma after chemoradiation occur within the first year, with 77% of any event occurring before year two. The data from individual time points suggest a reduction in follow-up during years 3-5 may provide adequate surveillance. Considering revisions of the current follow-up recommendations could maximize health care resources while also improving patient quality of life.
Survival of patients with metastatic HER2 positive gastroesophageal cancer treated with second-line chemotherapy plus trastuzumab or ramucirumab after progression on frontline chemotherapy plus trastuzumab.
Authors: Moser Justin , Solomon Benjamin , Nevala-Plagemann Christopher Duane , Gilcrease Glynn Weldon , Whisenant Jonathan R. , Garrido-Laguna Ignacio 
Published: January 2019

69 Background: Optimal second line treatment for patients with metastatic HER2 positive gastroesophageal cancer (Her2GE) is unknown. A retrospective study has suggested continuation of chemotherapy with trastuzumab (CT), as compared to chemotherapy alone, may improve outcomes. However, CT has never been compared to the current standard second-line treatment of chemotherapy plus ramucirumab (CR). Methods: The Flatiron Health EHR-derived database, a nationally representative database comprising patient-level structured and unstructured data, curated via technology-enabled abstraction, was reviewed for patients with metastatic Her2GE who received CT in the first line setting, followed by either second line CT or CR. Survival from second line therapy (SST) and time to next therapy or death (TTNTD) were compared using Kaplan-Meier curves and Log-Rank analysis. Demographics between treatment groups were compared using standard T tests and chi-squared analysis. Results: 135 patients were identified, of whom 34 received second-line CR and 101 received CT. Median SST for patients treated with CT was 10.2 months (m) [interquartile range (IQR) 5.1-20.8] and 6.8 m (IQR 3.2-20.2) for those treated with CR, p = 0.39. Median TTNTD for patients treated with CT versus CR was 4.9 m (IQR 2.8-9.8) and 4.8 m (IQR 2.3-7.5), respectively (p = 0.53). There was no difference between patients who received CT or CR in regards to average age (63 vs. 62, p = 0.72), average duration of first-line therapy (7.8 m vs. 9.1 m, p = 0.36), or percentage of patients with ECOG > 1 (15% vs. 22%, p = 0.50). Patients who received CT were more likely to receive a multiagent chemotherapy backbone (76% vs. 3%, p ≤ 0.001). Conclusions: This data suggest a non-significant trend towards increased SST for patients treated with second line CT versus CR. Further studies are needed to clarify optimal second-line treatment for this patient population.
Predictors of treatment response in colorectal high-grade neuroendocrine carcinomas (HGNEC): A single institution experience.
Authors: Corbett Virginia , Raj Nitya Prabhakar , Kelly Virginia , Reidy Diane Lauren 
Published: January 2019

690 Background: Colorectal high-grade neuroendocrine carcinomas (HGNEC) are aggressive tumors; treatment options consist of cis/carboplatin and 5FU-based chemotherapy. To date, choice of systemic therapy and sequencing of these drugs remains poorly understood. We examined clinical and molecular characteristics of colorectal HGNEC to better define predictors of response to cis/carboplatin and 5FU-based treatment. Methods: Patients (pts) with colorectal HGNEC treated at MSKCC from 1990-2018 were identified. MANEC (mixed adeno-neuroendocrine carcinoma) were excluded. Demographics, response to first- and second-line chemotherapy (by radiology report), outcomes, and molecular data (next-generation sequencing of tumor tissue), were collected. Results: 65 pts (mean age 58, 52% male) were identified, 13 (20%) with small cell carcinomas. 52 (79%) metastatic, 13 (20%) locally advanced. 27 (42%) received surgery and 11 (17%) received radiation. 56 pts received cis/carboplatin-based therapy, partial response (PR) in 18 (32%), stable disease (SD) in 4 (7%), and progressive disease (PD) in 31 (55%); 3 (5%) did not tolerate therapy. 28 pts received 5FU-based therapy, 13 PR in (46%), SD in 6 (21%), and PD in 7 (25%); 2 (7%) did not tolerate therapy. Median overall survival was 11.4 months. 21/65 (32%) pts underwent molecular sequencing of tumor; the most common alterations were KRAS 11 (52%), TP53 13 (62%), BRAF 7 (33%), APC 8 (38%), RB1 7 (33%). Most tumors (13/21, 62%) harbored alterations in genes traditionally altered in colorectal adenocarcinoma (KRAS/BRAF/APC) and in HGNEC (TP53/RB1). There was no significant difference in response to cis/carboplatin or 5FU-based chemotherapy based on location of the primary tumor (right vs. left) (p = 0.69/0.85), histologic features of the disease (p = 0.71/0.87), and for response to cis/carboplatin by molecular alterations in KRAS (p = 0.94), BRAF (p = 0.24), APC (p = 0.28), TP53 (p = 0.58), or RB1 (p = 0.28). Conclusions: Colorectal HGNEC are highly aggressive and more effective therapies are desperately needed. In this series, OS was poor. Clinical and molecular characteristics failed to predict response to cis/carboplatin and 5FU-based chemotherapy.
Disease characteristics and treatment outcomes of young colorectal cancer patients.
Authors: Parekh Hiral D. , Wang Yu , Hanayneh Wissam , Cameron Miles , Tan Sanda , Iqbal Atif , Read Thomas , Allegra Carmen Joseph , George Thomas J. 
Published: January 2019

691 Background: The incidence of colorectal cancer (CRC) in young patients (< 50 years) is increasing but little is known about disease characteristics and treatment outcomes in this patient population. Methods: CRC patients diagnosed at < 50 years of age (UF institutional registry 2000-2017) constituted the IRB approved study cohort. Statistical methods included descriptive statistics, uni-variable cox proportional hazard regression model, Pearson chi-square exact and Wilcoxon rank-sum test. Results: The median age at diagnosis was 45 years (range 17-50, n = 286) with 212 (74%) diagnosed between age 40-50. One third (35.7%) of patients had rectal primary and most common histology was adenocarcinoma (ACa, 84.6%) and 20% of those had poorly differentiated tumor. More than half of patients had an advanced primary (T3/T4, 65%) and 44% had lymph node positive disease. A trend towards increased delivery of perioperative therapy was seen in early staged disease. (See table) Patients who underwent curative resections had better hemoglobin (p = 0.005) and albumin levels (Alb, p < 0.001) and lower CEA level (p < 0.001). Factors associated poor survival were low alb levels ≤ 34 g/l, advanced primary tumor (T3/T4), nodal disease (N1/N2) and presence of diffuse metastasis. For stage 4 disease, the cancer-specific survival (CSS) at 1 year was 77.2%, 3-year CSS was 46.1% and 5-year CSS was 29%; survival was better (HR = 0.4; 95% CI 0.2-0.6, p < 0.001) among patients who underwent metastatectomy. Conclusions: Our data suggests that younger CRC patients were more likely to be managed in an aggressive manner with a higher proportion of early stage patients receiving perioperative therapy. A suggestion of an improved CSS was seen in advanced stage disease even with similar prognostic factors. Review of larger datasets are warranted. [Table: see text]
Organ preservation in rectal cancer patients treated with total neoadjuvant therapy.
Authors: Jimenez-Rodriguez Rosa Maria , Quezada-Diaz Felipe Fernando , Hameed Irbaz , Patil Sujata , Smith Jesse Joshua , Garcia-Aguilar Julio 
Published: January 2019

692 Background: Retrospective case series suggest that watch-and-wait (WW) is a safe alternative to total mesorectal excision (TME) in selected patients with a clinical complete response (cCR) after chemoradiotherapy (CRT). Because treatment strategies vary widely and total numbers of patients treated at different institutions have not been reported, the proportion of rectal cancer patients who can potentially benefit from WW is not known. Here, we report the results of a treatment strategy incorporating WW in a cohort of rectal cancer patients treated with total neoadjuvant therapy (TNT). Methods: Consecutive patients with stage II/III (MRI staging) rectal adenocarcinoma treated with TNT from 2012 to 2017 by a single surgeon were included. TNT consisted of mFOLFOX6 (8 cycles) or CapeOX (5 cycles) either before or after CRT (5600 cGy in 28 fractions with sensitizing fluorouracil or capecitabine). Tumor response was assessed with a digital rectal exam, endoscopy, and MRI according to predefined criteria. Patients with a cCR were offered WW, and patients with residual tumor were offered TME. WW and TME patients were compared based on intention to treat, using the chi-square or rank sum test. Relapse-free survival (RFS) was evaluated by Kaplan-Meier analysis. Results: A total of 109 patients were identified. One patient died during CRT. Of the 108 patients, 64 (59%) had an incomplete clinical response; 4 of the 64 patients declined surgery or had local excision, and 60 underwent TME. The remaining 44 patients (41%) had a cCR and underwent WW. On average, patients in the WW group were older and had smaller, more distal tumors. Median radiation dose, number of chemotherapy cycles, number ofadverse events, or length of follow-up (28 months) did not differ between the TME and WW groups. Five (11%) of the 44 WW patients had local tumor regrowth, at a median of 14 (4–25) months after TNT; 2 of the 5 also had distant metastasis. Six (10%) of the 60 TME patients had a pathological complete response. RFS did not differ between the TME and WW groups (log rank P= 0.09). Conclusions: Approximately 40% of patients with stage II/III rectal cancer treated with TNT achieve a clinical complete response and can benefit from a WW approach with the aim of preserving the rectum.
Gastrostomy tube for nutrition and bowel obstruction in patients with advanced malignancy: Less is more.
Authors: Gauvin Gabrielle , Do-Nguyen Chi Chi , Selesner Leigh T , O'Halloran Eileen , Lou Johanna , Collins Molly , Farma Jeffrey M. 
Published: January 2019

700 Background: Malnutrition and malignant bowel obstruction (MBO) are common consequences of advanced malignancy. Both lead to a poor prognosis, frequent hospitalizations, and have a negative impact on quality of life. The aim of this study is to explore gastrostomy tube (g-tube) placement practices to better define the role of g-tube role in advanced malignancy. Methods: Patients who underwent g-tube placement at our tertiary cancer care center between 2013 and 2017 were included in this study. Patients’ demographics, diagnosis, procedures, postoperative course, and clinical data were collected. Complications and survival were used as endpoints. Results: Two hundred forty-two cancer patients with an average age at diagnosis of 61 years (range 21-94) underwent g-tube placement for nutrition (76.4%), decompression (MBO) (22.7%), or both (0.8%). Active treatment within 3 months of g-tube insertion was seen in 37.8% of the nutrition group versus 29.1% in the MBO group (p = 0.208). Successful insertion was achieved in 96.8% of patients, but nine patients required more than one method of insertion attempt. In the nutrition group, successful method of insertion was 88.1% in interventional radiology, 8.1% in operating room, and 3.8% in endoscopy suite, compared to 81.8%, 14.5%, and 3.6% for the MBO group, respectively (p = 0.426). Post-placement complications were significantly less common in the MBO group compared to the nutrition group (24.1 vs. 54.3%, p < 0.001). Consultation pattern in the MBO group revealed that 45.5% had a palliative care consult, 56.4% were seen by social work, and 47.3% went to hospice. Survival in the MBO group was significantly shorter than in the nutrition group at 30 days (52.7 vs. 90.3%, p < 0.001), 1-year (54.6 vs. 5.9%, p<0.001), and three years (24.1 vs 1.8%, p = 0.001) after g-tube placement. Conclusions: In our experience, most patients who undergo g-tube insertion are not receiving active treatment and a large proportion of patients who receive a decompressive g-tube have a life expectancy of less than a month. These findings will inform the next step of our study: creating a discussion tool to coordinate better care and interventional decision making for patients with advanced malignancy.