tbuckley/cabot-search huggingface dataset:
The role of preoperative neoadjuvant cytoreductive dose-dense bevacizumab plus docetaxel followed by bevacizumab-doxorubicin-cyclophosphamide regimen in locally advanced operable breast cancer
Authors: S. E. Waintraub, V. Tuchman
Journal: Journal of Clinical Oncology (2009)

e11524 Background: Neoadjuvant Rx has been shown to downstage locally advanced breast cancer (LABC) to try to achieve a pathological complete response(PCR) and to convert mastectomy to lumpectomy. Bevacizumab (B) was recently approved to treat metastatic breast cancer in combination with paclitaxel (P). NSABP B-27 used preoperative doxorubicin(A) with cyclophosphamide (C) +- docetaxel (Doc) every 3 wks in primary operable breast cancer, yielding a 12.9% PCR with no residual invasive cancer from AC and 26.1% with the addition of Doc. Based on the success of E2100 with P+B over P, and the more recent AVADO trial showing the superiority of B and Doc over Doc, we have treated such Her2neu-neg pts using Doc/B followed by AC/B with a dose dense every (q) 2 week regimen to see if we could achieve a higher PCR rate and to assess the tolerability of this regimen. Methods: Pts with Her2neu-negative locally advanced operable M0 breast cancer were treated initially with B 10mg/kg iv q 2w with Doc 100mg/m2 q 2w four times with pegfilgrastim given 24 hours after chemotherapy, followed by A 60mg/m2 and C 600mg/m2 q 2 weeks four 4 times with pegfilgrastim given 24 hours after chemotherapy with B 10mg/kg iv for the first AC course as the B was discontinued at least 6 weeks prior to definitive breast surgery. All pts were to get radiation therapy after surgery and appropriate anti-estrogen Rx if estrogen receptor was positive. Results: 15 Her-2 neg women aged 35–61 were treated from 9/06-present for locally advanced primary operable breast cancer. All pts had clinically significant tumor reduction. Of the first 12 post-operative evaluable pts that have completed all the pre- operative therapy, the results showed 5 PCR, including one pt with residual sub-cm DCIS, 7 pathological incomplete responses, yielding a 42% PCR. 3 of the 5 PCR pts had lumpectomies. The major toxicity was excessive eye tearing, nail bed changes and lethargy. Conclusions: This novel dose dense q 2 week regimen is safe, tolerable and effective in LABC with acceptable toxicity. The addition of B to dose dense traditional neoadjuvant chemotherapy seems to increase the PCR. Larger prospective trials using B with dose dense therapy are warranted. No significant financial relationships to disclose.
A new prognostic staging system for pulmonary metastases from colorectal cancer.
Authors: Tomoichiro Hirosawa, Michio Itabashi, Yoshiko Bamba, Shimpei Ogawa, Kenichi Sugihara, Shingo Kameoka
Journal: Journal of Clinical Oncology (2014)

454 Background: A number of studies have examined the prognostic factors associated with pulmonary metastases of colorectal carcinoma (CRC). However, it has not yet been clarified which factor to emphasize taking the treatment strategy into consideration. Methods: The baseline characteristics and outcomes on 352 CRC patients undergoing complete pulmonary resection were collected from 19 institutions by the Japanese Society for Cancer of the Colon and Rectum (JSCCR) Study Group (Group A). The clinical and pathological factors were entered into a multivariate analysis to identify independent variables that were helpful for accurately predicting the long-term prognoses after pulmonary resection. Using the prognostic factors of Group A and the following processes (1) to (3), we developed and examined a new prognostic staging system (PSS): (1) Pulmonary (PUL) staging was performed using only pulmonary metastases-related factors in order to further clarify the prognosis. (2) The PSS was created using the PUL staging, primary cancer-related factors and hepatic metastases-related factors. (3) The new PSS was examined in a validation study in a series of 944 patients from 110 institutions of the JSCCR by the 78th society of the JSCCR (Group B). Results: (1) PUL1a: No. of metastases (No.) = 1 and DFI &gt; 2 years;(The 5-year OS: 66.7%, RFS rates: 52.8%). PUL1b: No. = 1 and DFI ≤ 2 years or No. = 2 or No. ≥ 3 and a unilateral distribution; (47.4%, 30.7%). PUL2:No. ≥ 3 and a bilateral distribution or the presence of lymph node metastases or pleural dissemination; (17.4%, 11.1%), (p&lt;0.01). (2) Grade A: PUL1a and lymph node metastases of N0, N1 or N2, or PUL1b and N0; (75.4%, 55.1%). Grade B: PUL1a and N3 or hepatic metastases cases or PUL1b and N1 or N2; (52.0%, 30.8%). Grade C: PUL1b and N3 or hepatic metastases cases or PUL2; (18.2%, 9.0%), (p&lt;0.01). (3) Grade A (n=324): 75.3%, 53.7%; Grade B (n=359): 60.8%, 41.5% and Grade C (n=261): 48.2%, 21.9%. (p&lt;0.01). Conclusions: Our new PSS was useful for the selection of patients suitable for pulmonary resection.
Adjuvant chemotherapy following neoadjuvant chemoradiotherapy and surgery for locally advanced rectal cancer.
Authors: Kirsten Elizabeth Jean Laws, Christina Wilson, David McIntosh, Stephen Harrow
Journal: Journal of Clinical Oncology (2014)

626 Background: Established guidelines exist for indications of adjuvant chemotherapy in colon cancer. However, in patients receiving neoadjuvant chemoradiotherapy for locally advanced rectal cancer, the benefit of adjuvant chemotherapy remains unproven. We evaluated clinical decision making behind adjuvant chemotherapy for locally advanced rectal cancer patients in our institute. Methods: Patients treated with long course chemoradiotherapy between January 2008 and December 2009 were identified. Exclusion criteria were inoperable disease, postoperative, recurrence, or palliative intent. 231 cases were examined retrospectively for the decisions behind giving or withholding adjuvant chemotherapy. Results: 35 (15%) were ineligible for consideration of adjuvant chemotherapy due to disease progression. 38 patients (16.4%) received chemotherapy in the adjuvant setting and 158 patients (68.4%) were potentially eligible for adjuvant chemotherapy, but did not receive it. The majority of clinicians based their decisions on post operative pathology results, and the key factor in decision making was final pathological stage in 65%. Clinicians considered pre-treatment imaging a key factor in only 14% of cases, despite a considerable number of patients being downstaged from a potentially higher initial pre-treatment stage that could have warranted adjuvant treatment. A considerable number of patients (25%) were deemed unfit for adjuvant treatment following neoadjuvant chemoradiotherapy and surgery due to toxicity of combined treatment. Conclusions: This analysis highlights the difficulty in clinical decision making for adjuvant chemotherapy in rectal cancer. The accuracy of pre-treatment staging is difficult to ascertain and its use to justify post operative treatment uncertain. It appears the majority of clinicians in our institute base their decision on post operative pathology. A considerable number of patients were not fit for consideration of adjuvant treatment due to toxicity of previous treatment. Further research is warranted as to the benefits of adjuvant chemotherapy, particularly in a setting where prior treatment already causes significant toxicity.
Feasibility and impact on resectability of FOLFIRINOX in locally-advanced and borderline pancreatic cancer.
Authors: Fabienne Portales, Benedicte Gagniard, Simon Thezenas, Emmanuelle Samalin, Eric Assenat, Matthias Alline, Pierre-Emmanuel Colombo, Philippe Rouanet, Sebastien Carrere, François Quenet, Olivier Riou, Carmen Llacer, Thibault Mazard, Marc Ychou
Journal: Journal of Clinical Oncology (2016)

e15708 Background: Pancreatic cancer (PC) has a poor prognostic. Only patients who undergo a complete R0 surgery have longer survival rates. Treatment of locally-advanced (LA) and borderline (BL) PC is controversial. Folfirinox is considered as a standard first-line treatment in metastatic patients. The aim of our study was to evaluate the impact of Folfirinox in LA and BL PC. Methods: We performed a retrospective analysis of prospectively-collected data from LA and BL PC patients treated with original Folfirinox in our institution between January 2010 and February 2015. Results: 35 patients were enrolled, 20 (57.1%) pancreatic head adenocarcinoma, 19 (54.3%) LA and 16 (45.7%) BL PC. There were 54.3% male, median age was 60 [44-74]. OMS was 0, 1, 2 for 21 (61.8%), 11 (32.4%), 2 (5.9%) patients. Median CA19.9 level was 5N [1-33]. All patients had Folfirinox in first-line followed by radiochemotherapy (RTCT) in 23 (65.7%) patients, with Gemzar and Xeloda in 21 and 2 patients. Median number of chemotherapy cycles was 4 [1-13]. The grade 3-4 toxicity rate was 17.1% (n = 6), mainly digestive (67%), hematologic (16.7%), none neurologic. There was no toxic death. 17 (46%) patients underwent surgery, 7 LA and 10 BL, with a R0 resection in 13 patients, mainly 8 PT3 (57.1%), no PT0, and 14N+. The morbidity rate was 40%, including 3 fistulae and 2 hemorrhages. Median overall survival was 24 months (95%CI: 14-44): 53 (95%CI: 26-.) and 12 months (95%CI: 9-19) in surgery vs no-surgery patients (p< 0.001). Progression-free survival was 13.9 months (95%CI: 11.2-17.1): 16.2 (95%CI: 13.7-25.3) and 9.5 (95%CI: 7.4-15.9) months in surgery vsno-surgery patients. 13 patients were still alive at the time of analysis, with a median follow-up of 44 months (95%CI: 7-53). 30 patients had disease progression, locally, distant or both in 7 (24.1%), 20 (69.0%) and 3 (13.1%) patients. Weight loss, OMS status, abdominal pain and CA19.9 level at diagnosis were not correlated with better survival. Conclusions: Folfirinox, followed or not by RTCT, as inductive treatment for LA and BL PC is feasible with acceptable toxicity, and allowed resectability in 37.1% patients, and thus a longer survival. Further studies are needed to confirm these encouraging results.
Clinical and Pharmacokinetic Results of a Four-Day Continuous Infusion of Full-Dose Busulfan in Patients (pts) Undergoing Matched Related (MRD) or Unrelated (MUD) Stem Cell Transplant (SCT).
Authors: Thomas C. Shea, Christine Walko, Don Gabriel, Jon Serody, Terrance Comeau, Robert Irons, Andrew Gilman, Carol Krasnov, Andrew Sharf, Celeste Lindley
Journal: Blood (2005)
Baseline GFR and cisplatin-induced renal toxicity in urothelial cancer patients.
Authors: Adrienne Tran, Janice Loh, Lingyun Ji, Siamak Daneshmand, Anne K. Schuckman, Susan G. Groshen, David I. Quinn, Tanya B. Dorff
Journal: Journal of Clinical Oncology (2016)

380 Background: Cisplatin eligibility for clinical trials has been defined as calculated GFR &gt; 60 mL/min due to risk of nephrotoxicity in patients (pts) with renal impairment. For urothelial cancer (UCa), substitution of cisplatin compromises outcomes. We evaluated change in GFR in pts treated with cisplatin despite baseline GFR &lt; 60 to determine risk of nephrotoxicity. Methods: 150 USC pts were identified who received systemic therapy for UCa from 2009 to 2014. Creatinine and weight values closest to treatment start and finish were used for calculation of GFR using the Cockcroft-Gault formula. Wilcoxon rank-sum tests and analyses of variance (ANOVA) were used to compare GFR percent change by age ( &lt; 75 vs &gt; 75 years), pre-treatment GFR ( &lt; 60 vs &gt; 60), therapy setting (neoadjuvant, adjuvant, or metastatic), primary disease site, and comorbidities (diabetes, hypertension, hyperlipidemia). Log-rank tests and Cox regression models were used to examine the association between overall survival (OS) and age or GFR. Results: 114 received cisplatin-based therapy at least once; 26 in the neo-adjuvant setting, 27 adjuvant, and 61 for metastatic disease. GFR could be calculated pre- and post-treatment for 81 pts; lowest GFR in pt receiving cisplatin was 25.5 mL/min. Median GFR change was -1.6% (range: -50% ~ 49%) for pts with pre-treatment GFR &lt; 60 compared to -10.9% (range -72%, 135%) for pts with pre-treatment GFR &gt; 60 (p = 0.17). Treatment setting (neo-adjuvant, adjuvant, or metastatic) had significant association with GFR change (p = 0.027). Median (range) of GFR change for the neo-adjuvant setting, adjuvant setting and metastatic setting was 4.6% (95% CI -32%, 90%), -5.8% (95% CI-39%, 20%), -11.9% (95% CI -72%, 135%), respectively. Age, primary disease site, diabetes, hypertension and hyperlipidemia were not associated with GFR change. Univariate analysis showed an association between GFR &gt; 60 at stop of treatment with worse OS (p = 0.087) in metastatic pts. Conclusions: Our data support the hypothesis that UCa pts with GFR &lt; 60 do not experience a greater decline in renal function after cisplatin treatment compared to patients with GFR &gt; 60. If validated, this may extend the option of cisplatin-based therapy to previously ineligible pts.
Use of total parenteral nutrition (TPN) in terminally ill gastrointestinal (GI) cancer patients (pts) compared to other malignancies (OM): A single-institution experience.
Authors: Margaret Cass-Garcia, Pamela Joy Hodul, Khaldoun Almhanna
Journal: Journal of Clinical Oncology (2013)

309 Background: TPN is increasingly used in terminally ill cancer patients. The purpose of this study is to determine the validity of TPN in terminally ill GI cancer patients compared to OM. Methods: Cancer pts with limited life expectancy were given TPN between 2007 and 2012. Patients had advanced stage cancer with inoperable non-functional GI tract or failure to thrive. The primary outcome was survival from time of initiating TPN. Results: 89 pts were started on TPN (57 with GI cancer and 32 with OM). The majority of OM were GYN cancer. The mean age was 56 in the GI group vs. 58 in the OM. 47% of all patients underwent treatment while on TPN. The median duration of TPN was 38 days (39 days in the GI group vs. 52 days in the OM group). The median time from TPN to death was 70 days (55 days in the GI group vs. 77 days in the MO group). 14 patients had restored bowel function. 3 patients are living and only one is on TPN. 26 pts required palliative gastrostomy tube. TPN complication was high with 68% of pts requiring readmission, many were admitted several times. Conclusions: Terminal cancer patients receiving TPN had a median survival of 70 days; survival was shorter in the GI cancer group. Quality of life did not improve in the majority of patients; nor did it influence ultimate outcome. These data, thus, raise the question of the validity of the use of TPN in terminally ill pts.
Photodynamic therapy (PDT) in the multidisciplinary treatment of brain tumors: A feasibility study.
Authors: M. S. Gonzalez, V. Vanaclocha, I. Azinovic, J. Rebollo, R. Cañon, E. Calvo, A. Brugarolas
Journal: Journal of Clinical Oncology (2011)

2094 Background: Usual treatment of brain tumors includes surgery, radiotherapy and chemotherapy, but the general prognosis is bad, with local relapse as the main cause of death. PDT is a local anticancer treatment that has showed promising results in other tumors (GI, H&N, etc) and can be administered in addition to the classical modalities. Methods: Patients (pts) diagnosed of primary, relapsed or metastatic (mets) brain tumors received an endovenous photosensitizer agent (Photofrin or Foscan). After a 2-4 days period, the tumor was removed. The residual cavity was exposed to a special laser during a predetermined time, in order to achieve the optimal activation of the photosensitizer that, once activated, kills the residual tumor cells. Complementary treatment with radio and chemotherapy was also administered after surgical recovery. Results: From December 2000 to January 2011, 51 pts (34 M/ 17 F; age 13-73, median 51) were treated with a total of 61 procedures (22 Photofrin, 39 Foscan). Diagnoses were glioblastoma (20), gliosarcoma (1), anaplastic astrocitoma (9), grade 2 astrocitoma (7), oligodendroglioma (6, 2 anaplastic), malignant meningioma (1), lung ca. mets (4), breast ca. mets (3). 18/44 primary CNS tumor pts had PDT at the initial resection procedure and 32 procedures were performed at the time of relapse. In 10 cases a second procedure was performed after relapse. Toxicity: 2 pts with thalamic gliomas died in the first 24 h; 6 pts presented postoperative neurological alterations, recovering in 3 to 17 days, and 4 pts presented cutaneous ulcerations related to the PDT, one of them requiring plastic surgery. Median OS of the treated primary brain tumors was 13 m (0-120+) and 8 pts are alive at 1+, 71+, 92+, 93+, 96+, 98+, 104+, and 120+ m (1 GBM, 1 AA, 3 grade 2 A, 3 OD). Conclusions: PDT can be safely used in the multidisciplinary treatment of brain tumors. In this group of heavily treated pts, it clearly benefits some of them, showing an improvement in OS over expected from historical data. Further studies are warranted.
Assessing intratumor heterogeneity and evolutionary distance in exome sequencing of colon cancer.
Authors: Ulrich Popper, Holger Rumpold
Journal: Journal of Clinical Oncology (2016)

590 Background: Carcinogenesis is considered to be an evolutionary process by natural selection of cell clones which have acquired advantageous heritable characteristics. This adaption process, which resembles Darwin’s evolutionary theory, has also been suggested as a potential mechanism promoting resistance to anti-cancer treatment. Methods: We performed whole exome sequencing of four colon cancers at five morphologically different loci of the primary tumor tissue. To investigate intratumor heterogeneity we conducted structural variant analysis, copy number analysis and ploidy profiling. We propose an evolutionary distance of the tumor samples based on a distance function in copy number space. Results: Copy number and phylogenetic analysis demonstrated substantial intratumor heterogeneity, with all 20 samples (5 loci for 4 tumors) possessing a unique copy number profile. Our analysis further revealed cancer-specific, tumor-specific and locus-specific copy number variants. We found that at least one copy of 18q, including the genes DCC and SMAD4, as well as 8p, carrying the CSMD1 gene, was missing in all tumors. Additionally, gains of chromosome 7,8q, 13q, 20q and losses of 4q and 21q were frequent. Using our distance measure in copy number space, phylogenetic analysis grouped together the five loci of one tumor and showed their evolutionary branching. We found that our distance measure in copy number space is superior to a distance measure in SNV space for colon cancer. Conclusions: Our analysis reveals that the landscape of the tumor genome cannot be captured by single tumor-biopsy, which is one of the challenges to personalized-medicine as heterogeneity can lead to therapeutic failures. However, there can be characteristics of the tumor genomes that are stable across samples which can potentially be used as biomarkers. Nonetheless variability of copy number profiles of colorectal cancers might suggest a personalized therapy.
Treatment of adenocortical carcinoma: 11-year Birmingham experience.
Authors: Lenka Zvirinska, Alice Tew, Emilio Porfiri
Journal: Journal of Clinical Oncology (2013)

462 Background: Due to the lack of prospective randomized phase III trial data, we have analysed patients with ACC treated between 2000 and 2011. Methods: All the patients given Mitotane (standard treatment of ACC in UHB, Birmingham) where extracted from pharmacy database. Results: 23 patients were identified, age 26-74 (median 53). Follow-up for whole group was 14–167m, median 60. Overall survival (OS) was 3-48m, medium 11.1 patient with slowly growing disease is still alive (167m) with 2nd dg of breast cancer. 19 patients were treated for metastatic disease, 4 in adjuvant setting. 7 patients were managed by endocrinologist only (3 adjuvant, 2 poor PS, 1 reluctant to treatment and 1 details unknown). 16 patients were under shared care. 4 these patients were never exposed to chemotherapy (2 poor PS, 1 returned to Africa, died within 5 months, 1 declined chemotherapy, still alive at 16 months post). 6/19 metastatic patients had chemotherapy as 1st treatment (4 patients etoposide/doxorubicin/cisplatin chemotherapy, 1 etoposide/carboplatin, 1 etoposide/cisplatin), 7 were treated with chemotherapy on PD(6 streptozocin, 1 etoposide/doxorubicin/cisplatin, 1 etoposide/cisplatin). There was no significant difference in OS when those approaches were compared (1st group 7-16 m, median 10, 2nd group 3-14, median 11) But TTP has been slightly worse for treatment on PD as expected (1st group 3-13m, median 6.5; 2nd group 3-14, median 3), although might be due to tendency to use Streptozocin, consistant with preliminary published results of FIRMACT trial.3 patients were treated with 2 lines of chemotherapy (age 30,31, 38), TTP 2- 5 m. Adjuvant patients within our sample has been followed up for limited perion only (11 – 71m, median 22.5), however no recurrence was diagnosed so far.In metastatic patient population 4 patients were treated for recurrence with time to relapse 3-43m, medium 23.5. Conclusions: ACC is heterogenic disease as confirmed by our survival data. In unselected population median OS is comparable to FIRMACT. Consistant with literature review, chemotherapy threatment can be delivered as 1st-line or delayed till PD. 2nd-line chemotherapy is of limited efficacy.
Bleeding events and eligibility requirements in studies evaluating an antiangiogenic agent in hepatocellular carcinoma (HCC).
Authors: A. G. Duffy, T. Greten
Journal: Journal of Clinical Oncology (2011)

310 Background: The presence of cirrhosis means an increased baseline potential risk of bleeding in patients with HCC. With the establishment of sorafenib as a standard of care option this risk is further increased. Bleeding events might potentially become a bigger problem, when sorafenib is combined with other vascular targeting agents. Therefore standardized eligibility criteria across clinical trials are needed. Methods: We performed a review of all available studies evaluating an antiangiogenic agent either alone or in combination with another agent. The following variables were recorded: demographics, eligibility criteria re: platelet count, coagulation, CP status, endoscopic requirements, hemorrhagic events (any grade). Data tabulated and descriptive statistical analysis employed. Results: 30 studies were identified since 2005 involving a total of 2,416 pts. 19 studies were available as published manuscripts. 11 of the studies involved sorafenib, 8 bevacizumab, 4 sunitinib with the remainder involving other agents (brivanib, lenalidomide, TSU68, Linifanib, ramicirumab).Eligibility criteria range re: platelet count 40 – 150; INR 1 – 2.3; No study was identified which mandated endoscopy to outrule varices, apart from one study which did so after the occurrence of 2 variceal bleeds. Serious hemorrhagic event up to 13%. Conclusions: While the risk of hemorrhagic event in studies evaluating an antiangiogenic agent appears to be within an acceptable range, there are no standardized across-study eligibility criteria for this “at risk” population in terms of platelet count, prothrombin time, or endoscopic requirements. Future studies will need to address this issue in more detail, particularly when multiple vascular targeting agents are combined. No significant financial relationships to disclose.