tbuckley/cabot-search huggingface dataset:
Mixed photon and neutron radiotherapy given concurrently with chemotherapy in unresectable pancreatic cancer.
Authors: M. E. Christensen, P. Paximadis, A. F. Shields, P. A. Philip, D. W. Weaver, A. A. Konski
Journal: Journal of Clinical Oncology (2011)

328 Background: Unresectable tumors of the pancreas remain difficult to treat despite the advent of targeted radiotherapy and modern chemotherapy. Randomized trials exploring the efficacy of chemotherapy and radiation have demonstrated median survival of 9 to 11 months. These survival times have not improved appreciably in the modern era. The purpose of this study was to retrospectively review our institutional experience with unresectable pancreatic cancer treated with mixed photon-neutron radiotherapy given concurrently with chemotherapy. Methods: Thirteen patients with unresectable tumors of the pancreas were treated between 1993 and 2001. All patients were treated with mixed photon-neutron radiotherapy given concurrently with chemotherapy. Median photon dose was 39.6 Gy (30.6-45Gy) and median neutron dose was 8 nGy (7-9 nGy). 12 of 13 patients were treated with neoadjuvant chemotherapy, followed by 5-FU given concurrently with radiotherapy. Median survival, overall survival, and local control were calculated for all patients. Results: The median age of all patients was 65 years (46-75 years). Twelve patients had histologic diagnosis of adenocarcinoma, with the other having an islet cell carcinoma. All patients are now deceased. Median survival for all patients was 11.5 months (3.0-25.6 months). The 1 and 2- year overall survival was 46.2% and 7.7%, respectively. Local control of the primary tumor was excellent at 92.3%. The rate of distant metastasis was 76.9%. One patient experienced decline without documented recurrence. No grade ≥3 acute toxicities were reported. However, there were 2 grade 5 late toxicities, both caused by gastrointestinal bleeding. Conclusions: Our experience demonstrates that treatment of unresectable pancreatic tumors with mixed photon-neutron radiotherapy given concurrently with chemotherapy results in excellent local control, with survival time equivalent to or exceeding that demonstrated in previous series. With the added capability of intensity modulated neutron radiation therapy (IMNRT), the incidence of treatment-related morbidity may be improved while taking advantage of the superior tumor control that high-LET radiation may impart. No significant financial relationships to disclose.
Reproductive organ involvement in female patients undergoing radical cystectomy.
Authors: Hooman Djaladat, Eila C. Skinner, Gus Miranda, Jie Cai, Siamak Daneshmand
Journal: Journal of Clinical Oncology (2013)

274 Background: Anterior pelvic exenteration is traditionally the treatment of choice for women with invasive bladder carcinoma. Female reproductive organ involvement is reported to be low, but there is not enough evidence to abandon this part during radical surgery. We evaluated the pathological involvement of reproductive organs (RO) in female patients undergoing radical cystectomy for invasive bladder urothelial carcinoma. Methods: 2,098 patients with bladder cancer underwent cystectomy between 1971 and 2008 at USC, of whom 458 were female. 411 (90%) had urothelial and 47 had non-urothelial bladder cancer. The cohort of female cystectomy patients with pathologic RO involvement is reviewed and their RFS and OS are discussed. Results: In the TCC group, 20 patients (4.8%) had RO involvement by urothelial cancer (UC-RO); 10 (2.5%) had vaginal, 2 (0.5%) cervical and one (0.25%) only uterus involvement with the rest (7) having a combination. In non-UC group, only two (4%) had RO involvement. In the UC-RO cohort, median age was 71 yo (38-89). Only one patient (5%) underwent orthotopic diversion. 19 cases (95%) were high grade TCC. Clinical stage T4a was diagnosed in 25% of cases preoperatively. Associated CIS, multifocality, LVI and histologic type of cancer had no significant correlation with RO involvement. Patients with a palpable mass or hydronephrosis were 5 times more likely to have RO involvement (P&lt;0.001). RO involvement was associated with higher chance of positive lymph nodes (60%) (P=0.001). Three (15%) and seven (35%) patients underwent neo-adjuvant and adjuvant chemotherapy respectively. Urethral pathology was positive in 1 patient. 5 (25%) developed local recurrence and 9 (45%) developed distant metastasis at a median follow up of 12.2 yrs (0.1 to 35.5 yrs). Two-year RFS and five-year OS in UC-RO group were both 10%. Conclusions: The risk of RO involvement in female patients undergoing cystectomy for bladder cancer is about 5%, with the vagina being the most commonly involved organ. A palpable mass and/or hydronephrosis are a strong predictor of RO involvement, although other clinical criteria are not predictive.
Outcome comparison between bridge to surgery stenting and emergency surgery in stage II, III obstructive left colon cancer: A multicenter retrospective study.
Authors: Han-mo Yoo, Won-Kyung Kang
Journal: Journal of Clinical Oncology (2016)

747 Background: A SEMS (Self Expandable Metallic Stents) has been widely used for obstructive colorectal cancer as a bridge to surgery to avoid emergency surgery. However, it may increase the tumor spillage so that the long-term survival would be compromised. The aim of our study was to compare the short- and long-term outcome of surgery after stent insertion with those of emergency surgery alone for the left colon malignant obstruction patients. Methods: The medical records of patients who received curative resection due to obstructive primary left colon cancer and diagnosed to stage II or III from January 2004 to December 2010 in six hospitals affiliated to the Catholic Medical Center. Overall survival and disease free survival were compared between the SEMS (n = 158) and emergency surgery (n = 56) group. Short-term outcome was also compared. Factors affecting disease-free survival in the SEMS group were analyzed using the cox proportional hazards model. Results: Baseline characteristics were comparable between two groups by pathologic stage. Intra-operative complication (0.0% vs. 7.1%, p = 0.004), re-operation (1.3% vs. 7.1%, p = 0.042), post-operative hospital stay (11.2 ± 6.5 days vs. 14.6 ± 8.9 days, p = 0.010) and conversion rate (3.5% vs. 16.7%, p = 0.028) showed short-term advantages of the SEMS. 5-year DFS in stage II patients was 87.2% for the SMES group, 73.5% for the ES group (p = 0.117). Among stage III patients, 5-year DFS was 55.8% for the SEMS group and 72.0% for the ES group (p = 0.129). 5-year OS of the SEMS group was 90.2%, and of the ES group was 92.4% in stage II patients (p = 0.694). 5-year OS in the SEMS group was 82.8%, and the ES group 73.0% in stage III patients (p = 0.577). For the stage III SEMS patients, hospital of procedure (p = 0.041) and operation date (HR 0.400, 95% C.I 0.176-0.905, p = 0.028) were independent factors on disease free survival. Conclusions: If there’s an intervention team with sufficient experience for the SEMS and a sufficient preparation for emergency surgery, the SEMS is a good therapeutic option for malignant obstruction in left colon cancer.
Activity and safety of gefitinib and erlotinib in metastatic non-small cell lung cancer (NSCLC): A comparative analysis.
Authors: T. Franchina, B. Adamo, N. Caristi, G. Chiofalo, G. Toscano, F. Colonese, N. Denaro, G. R. Ricciardi, A. Russo, V. Adamo
Journal: Journal of Clinical Oncology (2010)

e18110 Background: Gefinitib and erlotinib have been used with variable benefit in NSCLC. We have analyzed outcome data of 82 patients that received these TKIs to determine and compare the benefit derived and the safety profile. Methods: We used gefitinib in a compassionate-use program (October 2002-March 2007) for pretreated NSCLC pts. In this setting 42 metastatic pts received oral gefitinib at dose 250 mg/mq daily. Pts (33M, 9F) had a median age of 64.7 years (range 22-81). ECOG PS 0/1/2:17/18/7. Histology was squamous carcinoma 13/42, adenocarcinoma 20/42, bronchioalveolar 1/42, undifferentiated 8/42. Smokers were 33/42. Gefitinib was second line in 20 pts and third line in 22. As regards erlotinib 40 pts were treated from November 2006 to December 2008 receiving a standard oral daily dose of 150 mg. The pts (25M,15F) had a median age of 63.9 years (range 42-80). ECOG PS 0/1/2:10/17/13. Histology was: squamous carcinoma 17/40, adenocarcinoma 17/40, bronchioalveaolar 2/40, undifferentiated 4/40. Smokers were 27/40. Erlotinib was second line in 20 pts and third line in 20. Results: The median duration of gefitinib therapy was 7.2 months, RR was 71% (SD 57%) and median survival was 12.7 months (range 2-51). Median duration of erlotinib treatment was 6.4 months, RR was 60% (SD 40%) and median survival was 11.7 months (range 2-40+). The main side effects of both EGFR TKI were grade 1-2 diarrhoea, skin rash and xerosis. We recorded for erlotinib only a G3 rash and an increase of bilirubinemia in a pts with Gilbert syndrome, instead with gefitinib G3 rash was observed in 3 pts and G4 in 2 pts. Conclusions: From our results erlotinib and gefitinib are well tolerated and obtain a good disease control in these poor prognosis pts. In gefitinib treated patients a more relevant number of stable diseases and a longer median survival were recorded, but also more cases of severe skin rash than erlotinib. No significant financial relationships to disclose.
Baseline Thrombophilic Alterations and Risk of Venous Thromboembolism in 266 Multiple Myeloma Patients Primarily Treated with Thalidomide and High-Dose Dexamethasone.
Authors: Elena Zamagni, Lelia Valdre, Michela Cini, Cristina Legnani, Patrizia Tosi, Paola Tacchetti, Francesca Patriarca, Michela Ceccolini, Lucio Catalano, Elisa Favaretto, Francesco Casulli, Silvestro Volpe, Giulia Perrone, Luciano Masini, Antonio Ledda, Sadia Falcioni, Annamaria Brioli, Alessandro Gozzetti, Catello Califano, Mariacaterina Pallotti, Claudia Cellini, Affra Carubelli, Lucia Pantani, Michele Baccarani, Gualtiero Palareti, Michele Cavo
Journal: Blood (2007)
Quantitative measurements of p95HER2 (p95) and total HER2 (H2T) protein expression in patients with trastuzumab-treated, metastatic breast cancer (MBC): Independent confirmation of clinical cutoffs.
Authors: W. Biernat, R. Duchnowska, B. Szostakiewicz, J. Sperinde, M. Haddad, A. Paquet, Y. Lie, J. Weidler, W. Huang, J. Winslow, T. Jankowski, B. Arlukowicz-Czartoryska, P. J. Wysocki, M. Foszczynska-Kloda, B. Radecka, M. M. Litwiniuk, S. Debska, M. Bates, J. Jassem
Journal: Journal of Clinical Oncology (2011)

586 Background: Expression of p95 in HER2-positive breast cancer patients is potentially a major determinant of trastuzumab resistance because p95 lacks the trastuzumab binding site while retaining kinase activity, and is associated with poor prognosis. Previously, optimal cutoffs for p95 (Clin Cancer Res, 16:4226, 2010) and H2T (Cancer, 116:5168, 2010) were defined in a training set of trastuzumab-treated MBC patients. Methods: Quantitative H2T and p95 assays (VeraTag, Monogram Biosciences) were retrospectively performed on formalin-fixed, paraffin-embedded samples from an independent series of 142 trastuzumab-treated MBC patients. Previously-defined cutoffs for H2T and p95 were tested to determine whether H2T above the cutoff correlated with better outcomes and whether p95 above the cutoff in the HER2-positive subset correlated with worse outcomes, as had been observed in the training dataset. Results: H2T above the pre-defined cutoff was found to correlate with longer progression-free survival (HR=0.61; p=0.044; stratified by hormone receptor status and tumor grade). Additionally, in the subset of patients assessed as H2T-positive, p95 values above the pre-defined cutoff correlated with shorter progression-free survival (HR=1.9; p=0.018; stratified by hormone receptor status). Conclusions: Optimal H2T and p95 cutoffs derived from a previous training dataset were confirmed in a second independent clinical series. The observed consistency in H2T and p95 cutoffs as measured by VeraTag (HERmark) across different cohorts of trastuzumab-treated MBC in two independent exploratory analyses justifies additional studies employing blinded analyses in larger series of patients, and are currently planned in order to formally validate these cutoffs.
Interim results of Intergroup EC-Doc Trial: A randomized multicenter phase III trial comparing adjuvant CEF/CMF to EC- docetaxel in patients with 1–3 positive lymph nodes
Authors: U. Nitz, J. B. Huober, B. Lisboa, N. Harbeck, H. Fischer, V. Moebus, G. Hoffmann, D. Augustin, E. Weiss, W. Kuhn
Journal: Journal of Clinical Oncology (2008)

515 Background: Taxanes and anthracyclines are the most active drugs in breast cancer. Taxane-based adjuvant chemotherapy is considered as standard in node-positive breast cancer, though a large body of evidence derives from trials testing taxanes versus a weak standard (4xAC). Subgroup analyses from several trials indicate that patients with 1 to 3 positive nodes, though at intermediate risk, will have a maximum benefit from taxane-based therapy. Methods: 2,011 patients with primary breast cancer and 1 to 3 positive lymph nodes were randomized from 3/2000 to 8/2005 to a phase III trial comparing 4 cycles E90C600 q3w followed by 4 cycles of docetaxel100 q3w (n=1,008) (Arm A) versus a control Arm B: 6 cycles of E100F500 C500 q3w (n=828) or C600M40F600 d 1 and 8 q4w (n=175). The primary endpoint was the event-free survival (EFS). Secondary endpoints were overall survival, toxicity and quality of life. EC-Doc trial has a 80% power to detect 5 % difference in 5-year EFS. Survival rates will be compared by one-sided log-rank and Cox proportional hazard test. Results: Baseline characteristics were well balanced between both study arms. Median age of patients was 51 years in both arms. Median tumor size 2.0 and 2.05 cm (arm A/B), 69% and 71% of tumors were ER positive (A/B). Toxicity data have been presented earlier (St. Gallen 2005). 312 severe adverse events have been reported (198 in EC/Doc and 114 in CEF/CMF patients). There were 3 therapy-related deaths (2 in arm A and 1 in arm B). At the median follow-up of three years blind analysis of first primary events (34 vs. 64) and deaths (17 vs. 36) was made, so that the independent data safety committee decided to present interim analysis of the trial. Conclusions: Our preliminary data strongly suggest a superiority of one study arm in terms of EFS and early OS in an intermediate risk group. We will present a completely updated survival analysis for the comparison of EC-Doc versus FEC/CMF. No significant financial relationships to disclose.
A systematic review of post first-line treatments for advanced gastrointestinal stromal tumor (GIST): Direct pairwise meta-analyses and indirect comparisons.
Authors: Keya Shah, Kelvin K. Chan, Yoo-Joung Ko
Journal: Journal of Clinical Oncology (2015)

195 Background: Treatment for metatastatic or unresectable GIST is with imatinib. The majority of patients eventually acquire imatinib resistance, prompting the development of a growing number of agents as post-first-line treatment. Currently no studies directly compare these treatments. Methods: A systematic review was performed through MEDLINE, EMBASE, CENTRAL, and ASCO meeting abstracts up to July 2014 to identify randomized controlled trials that included GIST patients who were previously treated with a first-line chemotherapy for advanced disease. Progression-free survival (PFS) and overall survival (OS) with 95% credible regions were extracted using the Parmar method. Direct pairwise meta-analyses and indirect comparisons using the Bucher method were performed. Results: Four studies were identified for the systematic review. 1 study (n=312) showed that sunitinib in the second-line setting (vs. placebo) improved PFS but not OS. 3 studies (n=528) examined the third-line setting (imatinib resumption vs. placebo; regorafenib vs. placebo; nilotinib vs. best supportive care with or without imatinib or sunitinib). Of the 3 third-line studies, there was significant heterogeneity between placebo-controlled trials and the non-placebo controlled trial (I 2 = 98%). Direct pairwise meta-analysis using random-effects of the 2 placebo-controlled studies showed that the PFS hazard ratio (HR) was 0.63 (0.22-0.61, p=0.0001), whereas the PFS HR for the non-placebo controlled study was 0.90 (0.65-1.26, p=0.56). These 2 HRs are different statistically (interaction: p=0.002). Indirect comparisons of imatinib resumption vs. regorafenib suggested that the PFS HR was 0.59 (0.31-1.11, p=0.10), trending in favor of regorafenib. OS HRs were not significant for direct or indirect comparison in the third-line setting. Conclusions: The number and size of completed phase III studies and the lack of a standard comparator arm limit the use of direct and indirect comparison methods to determine the best therapeutic option for patients who have progressed on imatinib. At this time, clinicians should interpret the available evidence at an individual level.
The utility of the surprise question in identifying patients most at risk of death.
Authors: Judith B Vick, Nate Pertsch, Mathilde Hutchings, Bridget A. Neville, Stu Lipsitz, Atul Gawande, Susan Block, Rachelle Bernacki
Journal: Journal of Clinical Oncology (2015)

8 Background: Understanding the cancer patient’s prognosis in all illness phases is important. Evidence suggests that the “Surprise Question” (SQ) -- “Would you be surprised if this patient died within the next year?” -- may be useful in identifying those most at risk of death, but prior studies are limited by the relatively small number of patients and clinicians included. Methods: From July 2012 to October 2014, oncology clinicians at Dana-Farber Cancer Institute were invited to enroll in a randomized controlled trial on the impact of a structured intervention to improve conversations about end-of-life goals -- the Serious Illness Care Program. The SQ was asked about each patient seen by the enrolled clinician. We used a weighted propensity score approach to calculate adjusted proportions of survival at 6 months and 1 year, clustering by SQ clinician. To determine which variable was most predictive of death, we fit a multivariable Cox model, and found the variable that led to the largest increase in the Cox-regression goodness-of-fit c-statistic. Results: 81 oncology clinicians (59 oncologists, 18 nurse practitioners, and 4 physician assistants) enrolled in the study and we had complete data on 4617 patients: 3821 (83%) for whom the clinician answered “Yes” to the SQ and 796 (17%) for whom the answer was “No.” Propensity-adjusted 1-year survival for “Yes” patients was 93% (95%CI 91-96%) compared to 53% (95%CI 46-60%) for the “No” patients (p &lt; 0.0001). The SQ was more predictive of patient death than type of cancer, age, cancer stage, or time since diagnosis. Sensitivity of the “No” response was 59% (95%CI 49-68%) and specificity was 90% (95%CI 86-93%). Positive predictive value was 49% (95%CI 45-54%) and negative predictive value was 93% (95%CI 90-95%). Conclusions: The Surprise Question identifies cancer-center patients at high risk of death within one year better than clinical variables such as cancer type, stage, patient age, or time since diagnosis.
Gemcitabine (G) and cisplatin (C) in a modified 3-week schedule for non-small cell lung cancer (NSCLC): Impact on hematologic toxicity and dose intensity (DI)
Authors: O. Caffo, V. Murgia, G. Ambrosini, S. Brugnara, A. Caldara, A. Ferro, M. Frisinghelli, B. Soini, F. Valduga, E. Galligioni
Journal: Journal of Clinical Oncology (2008)

19099 Background: The G+C combination is one of the most widely used treatments for NSCLC. Aimed to enhance DI and reduce toxicity, the original 4-week schedule has been generally modified into a 3-week schedule, decreasing the C dose from 100 to 75–80 mg/sqm and increasing the G dose was from 1000 mg/sqm to 1250 mg/sqm. Others have postponed the C administration from day 1 or 2 to day 8 or 15, in the 4-week schedule, but in the 3-week schedule C administered on day 1 or 2 may hamper the 8th day G dose, due to toxicity. This report presents our experience with a modified 3-week schedule, that we have adopted into the daily clinical practice. Methods: Our pts were treated with G (1000 mg/sqm) on days 1,8 and C on day 8 (100 mg/sqm until January 2004: 75 pts, or 75 mg/sqm from January 2004: 85 pts). The GCSF use was allowed, according to the pts clinical needs. The toxicity was recorded according to the NCIC-criteria. Results: from October, 2000 to October, 2007 a consecutive series of 160 stage IIIa-IV NSCLC pts (median age 61.5 yrs, range 31- 77) received CG as induction therapy for locally advanced (62 pts) or as palliative treatment for metastatic disease (98 pts). Overall, the pts received 630 chemotherapy courses (median 3, range 2–6, for locally advanced and 4, range 2–9, for metastatic pts). The median DI was 87% (range 34–100). Considering the 8th-day dose, 16% of the treatments were delayed due to hematologic toxicities, while in 17% of the cases a GCSF priming after day 1 was necessary. Grade 3–4 hematological toxicities (per pts) were: anemia 3.7%, leukopenia 7.5%, neutropenia 46.8%, thrombocytopenia 5%. In pts with locally advanced disease, a 71% response rate (RR) and 14 mos of median OS were observed. In metastatic pts the RR was 53% and the median OS was 11 mos. Conclusions: it appears from our experience, that our modified 3-weeks regimen, compared to others 3-weeks CG schedules, has provided a similar DI, is equally active and tolerated but with a better hematologic toxicity profile in terms of anemia and thrombocytopenia. No significant financial relationships to disclose.