tbuckley/cabot-search huggingface dataset:
EGFR and K-ras status and clinical outcomes in patients with advanced NSCLC treated with erlotinib: Our experience.
Authors: B. Di Cocco, M. Colonna, N. Salesi, M. Moscato, A. Calogero, L. Pacini, E. Veltri
Journal: Journal of Clinical Oncology (2011)

e18076 Background: The purpose of this analysis was to investigate in patients with advanced pre-treated NSCLC, the response to erlotinib, EGFR tyrosine kinase inhibitor (TKI), and EGFR and K-ras mutations. Methods: 63 patients with stage IIIB or IV non-small cell lung cancer, with performance status 0-2, previously treated with 1-2 chemotherapy regimens received erlotinib (150 mg oral daily). We also analyzed 63 tumor samples for EGFR/K-ras mutations by fluorescence in situ hybridization (FISH; EGFR gene copy number), and DNA sequencing (EGFR, KRAS gene mutations). Coprimary endpoints were overall response rate (ORR) and clinical benefit (CB) according to EGFR/K-ras status. Secondary endpoints were progression free survival (PFS) and safety. Results: Among 63 patients, 4 pts had a partial response (ORR 6.35%), with median duration of the response of 12 months (mo), 16 pts had a stable disease (SD 25.4%) with CB of 31.75%; PFS was 2.2 mo. 9 pts (14.2%) had EGFR mutations, 7 pts (11.1%) had K-ras mutations, 18 pts (28.5%) showed a high level of EGFR gene copy (FISH positive). 2 of 9 patients with EGFR mutation had a RP, 4 had a SD (66.6% CB) compared with 2 RP and 12 SD (CB 25.9%) in the group with wild type EGFR (54 pts). PFS of 9 pts with EGFR mutation was 8.5 mo. 3/18 pts EGFR FISH positive had RP. None of the 4 patients with a K-ras mutation (4.76%) had a tumor response. Only 3% of patients discontinued erlotinib because of toxic effects. Conclusions: According to the literature our data show that the presence of EGFR mutations seems to correlate with response to erlotinib with improved CB and PFS.
Secondary malignant neoplasms among children and adolescents following treatment for Hodgkin disease
Authors: D. A. Rokitka, P. Va, D. M. Green, M. C. Mahoney
Journal: Journal of Clinical Oncology (2008)

10055 Background: While 90% of patients diagnosed with Hodgkin disease (HD) during childhood are successfully treated, these patients remain at risk for late effects from these therapies. The objective of the current study was to evaluate the frequency of and risk factors for secondary malignant neoplasms (SMNs) among a cohort of HD patients who were treated at Roswell Park Cancer Institute (RPCI) between 1960 and 1989. Methods: This was a retrospective cohort study of 182 previously untreated patients with HD who were younger than 20 years of age at the time of diagnosis and were referred to RPCI between 1/1/1960 and 12/31/1989; follow-up extended through 12/31/2007. Sex- and age-specific person-years at risk were accumulated and applied to gender, age-, and time period-specific cancer incidence rates for New York State, excluding New York City. Standardized incidence ratios (SIRs), and 95% confidence intervals, were calculated for overall cancer incidence and by type of therapy. Results: Of 182 individuals with a history of HD, 27 persons (15%) developed at least one secondary malignancy (total malignancies=29) and 12 persons (7%) were diagnosed with basal cell carcinoma. Commonly observed malignancies included thyroid cancer (n=8, 28%), breast cancer (n=5, 17%), and non Hodgkin lymphoma (n=4, 14%). The SIR for SMNs was markedly elevated among both males (SIR 6.23, 95% CI=3.11–11.14) and females (SIR=6.26, CI=3.83–9.67). The SIR for BCC was also markedly elevated among both males (SIR 5.32, 95% CI=3.29–8.13) and females (SIR 3.62, CI=3.02–5.97). The occurrence of secondary malignancies did not vary by therapy (e.g., use of alkylating agents, use of doxorubicin, splenectomy, radiotherapy or any chemotherapy) or by relapse status, although the number of individuals treated with either radiation therapy only (N=10) or chemotherapy only (N=0) was too small to allow these effects to be separated. Conclusions: Results from this study have relevance to the clinical care of survivors of childhood HD and aid in quantifying the risk of SMNs. In addition, these findings underscore the importance of long term follow-up and clinician counseling regarding cancer screening/surveillance and healthy behaviors. No significant financial relationships to disclose.
Efficacy and feasibility of neoadjuvant chemotherapy for elderly patients with stage II/III esophageal cancer: Retrospective study.
Authors: Takahiro Miyamoto, Tetsuji Terazawa, Masahiro Goto, Ken Asaishi, Fukutaro Shimamoto, Shin Kuwakado, Hitoshi Nishitani, Takayuki Kii, Masaru Kawai, Kazuhide Higuchi
Journal: Journal of Clinical Oncology (2015)

220 Background: From the result of JCOG 9907 study, which showed the supremacy of neoadjuvant chemotherapy (NAC) of 5-fluorouracil plus cisplatin infusion (FP) over adjuvant chemotherapy, NAC FP is standard therapy for stage II or III esophageal cancer in Japan. However, the efficacy and feasibility of NAC FP for elderly patients (pts) still remains unclear. Methods: We examined stage II or III esophageal cancer patients aged 70 or over, who received NAC FP at our institution between April 2008 and August 2014, retrospectively. Results: 12 pts received NAC FP at least 1 course. The pts characteristics were as follows: median age (range), 73 (70-78); male/ female, 11/1; PS 0/1, 3/9. Location of primary tumor and clinical stage based on UICC 2009 were as follows: upper/middle/lower, 3/6/3; stage IIA/IIB/IIIA/IIIB, 3/3/3/3. 2 pts (16.7%) occurred grade3/4 neutropenia (16.7%). grade3/4 non-hematotoxicities were nausea; 2 pts (16.7%), vomiting; 1 pt (8.3%), appetite loss; 4 pts (33.3%), stomatitis; 1 pt (8.3%) and acute kidney injury; 1 pt (8.3%). 3 pts were underwent surgery after 1 course of NAC FP due to renal dysfunction. 3 pts were not performed surgery because of decreased respiratory function, decreased PS and progression disease. 9 pts were performed surgery after NAC FP. The histological efficacy was 1a/1b/2/3; 4/3/1/1 and curativity was R0 (degree A)/R0 (degree B); 8/1. 4 pts (44%) had down staging. Median follow-up time was 16.5 months (range; 4-63), the 5-year relapse free survival rate was 19.0% (95% CI: 2.7-66.4%) and the 5-year overall survival rate was 67% (95% CI: 32-89%). Conclusions: NAC FP for stage II/III esophageal cancer might be effective even in pts ≥70 years of age. However, gastrointestinal toxicity and renal toxicity were developed frequently, therefore the indication of NAC FP for elderly pts must be decided carefully.
Anxiety changes following initiation of treatment in older breast cancer (BrCa) patients
Authors: K. A. Bylow, W. Dale, S. Gupta, M. Lacy, M. Rodin
Journal: Journal of Clinical Oncology (2005)

8262 Background: Although anxiety levels decrease tolerance to chemotherapy (ctx) and quality of life (QOL), few studies have assessed longitudinal anxiety changes in older BrCa pts undergoing adjuvant treatment. Results from an ongoing prospective longitudinal study of the QOL and psychological effects of adjuvant treatment in older BrCa pts are reported. Methods: Pts ≥ 50 yrs of age with stage I-III BrCa and no prior cancer history or ctx were eligible for enrollment. All pts undergo surgical resection and receive adjuvant ctx and/or hormonal therapy per their oncologists’ recommendations. Anxiety was measured using the State-Trait Anxiety Inventory, a validated scale that distinguishes transient state anxiety (STAI-S) from background trait anxiety (STAI-T). In addition, geriatric measures of cognition (Mini-Mental State Examination [MMSE]) and functional status (instrumental activities of daily living [IADLs]) were collected. Assessments are administered at baseline, 6 mos, and are planned for 2 yrs. Anxiety levels were compared pairwise in pts at baseline (prior to the initiation of therapy) and at 6 mo (after starting therapy). Results: Pts (n=27) are older (mean = 70; range 56–80), predominantly non-caucasian (56%), not married (52%), and have a HS education level (mean = 13.4 yrs). They are cognitively intact (mean MMSE = 29), highly functional (96% with ECOG = 0; mean IADL score of 13/14), and not depressed (7%) at baseline and 6 mos. None of the sociodemographic measures were related to baseline anxiety levels, including age. Mean STAI-S scores decreased significantly from baseline to 6 mos (36.3 vs. 29.9; p=.002, Wilcoxon Signed Ranks Test), while mean STAI-T scores did not change. Pts on ctx were more anxious at baseline than those on hormonal therapy (STAI-S 43.9 vs. 33.6; p=.007), but not at 6 mos. In a multivariate, repeated-measures ANOVA controlling for age and therapy, STAI-S still decreased significantly. Conclusions: Older BrCa pts receiving adjuvant therapy experience a significant decrease in state anxiety following treatment initiation. Those receiving ctx vs hormonal therapy are more anxious at baseline. Older women with BrCa benefit from peace-of-mind with therapy initiation. No significant financial relationships to disclose.
Cumulative incidence of second neoplasms over 30 years after treatment of childhood acute lymphoblastic leukemia (ALL)
Authors: N. Hijiya, M. M. Hudson, S. Lensing, G. K. Rivera, B. I. Razzouk, R. C. Ribeiro, J. E. Rubnitz, J. T. Sandlund, M. V. Relling, C. H. Pui
Journal: Journal of Clinical Oncology (2005)

8537 Background: Little is known about the long-term incidence of second neoplasm after treatment of childhood ALL. The reported cumulative incidence of second neoplasm at 10 to 15 years after ALL treatment varies from 1.2% to 3.3%, but the incidence after 20 years has not been well studied. Methods: We conducted a retrospective study of 2304 patients with ALL treated between 1962 and 1998 to assess the long-term incidence of second neoplasm. Results: The median follow-up time was 17.8 years (range, 0.3 to 39.3 years). Second neoplasms developed in 167 patients (123 in initial remission, 44 after retrieval therapy) and comprised hematologic malignancies (61 myeloid, 5 lymphoma) and solid tumors (21 meningiomas, 26 other brain tumors, 24 basal cell carcinomas, 22 other carcinomas, 7 sarcomas, and 1 melanoma). For the 123 patients in whom a second neoplasm developed as the first event, the median time between diagnosis of ALL and development of a second neoplasm was 8.6 years (range, 0.5 to 31.7 years). All myeloid malignancies, lymphomas, and CNS tumors except meningiomas occurred within 17 years after diagnosis of ALL. The cumulative incidences were 4.1% (95% confidence interval [CI], 3.2%–5.0%) at 15 years for patients in first remission and 11.9% (95% CI, 8.9%–14.9%) at 30 years. When meningioma and basal cell carcinoma were excluded, the cumulative incidences were 3.9% (95% CI, 3.0%–4.7%) at 15 years for patients in first remission and 6.5% (95% CI, 4.6%–8.3%) at 30 years. Conclusions: The overall cumulative incidence of second neoplasm increases during the first 30 years after treatment. Follow-up over multiple decades is necessary to ascertain the incidence of second neoplasm after ALL treatment. No significant financial relationships to disclose.
Post-progression survival (PPS) and improvements in progression-free survival (PFS) in randomized controlled trials (RCTs) in advanced gastric cancer (AGC).
Authors: Kohei Shitara, Marc E. Buyse, Everardo D. Saad
Journal: Journal of Clinical Oncology (2013)

93 Background: Since PPS may influence overall survival (OS), studying PPS may help in understanding why gains in PFS do not always translate into gains in OS. Methods: We searched PubMed for RCTs on first-line therapy for AGC published between 01/82 and 01/12. We estimated mean PFS and OS (in months) using the area under the published Kaplan-Meier curves, computing mean PPS as mean OS minus mean PFS for each trial arm. We compared PPS between trial arms grouped according to PFS duration (longer versus shorter PFS, regardless of statistical significance) and world region (using t tests). Results: We retrieved 53 trials (25 were phase III, 24 were randomized phase II, and 4 had no explicit phase) enrolling 12,050 patients in 121 arms. We could estimate mean endpoints for 33 trials (26/6/1 with 2/3/4 arms), which were more likely to be phase III than the 20 trials with no Kaplan-Meier curves for both endpoints. The average mean PPS was almost identical between trial arms with longer or shorter PFS. Use of PPS assessed as median OS minus median PFS yielded qualitatively similar results. Conclusions: Treatments that improve PFS do not seem to influence PPS. Asian trials appear to have longer OS due to longer PPS, not PFS. Work with individual patient data collected worldwide by the GASTRIC group is under way to confirm our findings. [Table: see text]
Cancer-related insomnia: Evaluation by mobile technology.
Authors: Brenda O'Connor, Pauline Ui Dhuibhir, Declan Walsh
Journal: Journal of Clinical Oncology (2015)

107 Background: Insomnia is difficulty with sleep onset, maintenance, early morning wakening or non-restorative sleep. Cancer prevalence is 30-75%. Daytime consequences include fatigue. It is under-reported and impairs quality of life. Measurement previously required sleep laboratories. Technology advances help real-time measurement in the natural environment. This study investigated the feasibility and acceptability of a wireless device to evaluate sleep in cancer. Methods: Prospective observational study: Stage A: 10 consecutive in-patient hospice admissions; Stage B: 20 consecutive community patients Sleep quality was rated by Insomnia Severity Index (ISI). Participants used a wireless non-contact bedside monitor (SleepMinder) for 3 nights. Acceptability questionnaires were completed by participant and nurse (Stage A) or family (Stage B).Descriptive statistics were generated by Microsoft Excel. Results: 30 participants with metastatic cancer were recruited. Median age: 63 years (47-84). Median Eastern Cooperative Oncology Group (ECOG) performance score: 2 (0-3). In-patient (n=10): In 50%, sleep onset was delayed &gt;30 minutes. Median duration: 8 hours. Median awakenings per night: 1 (0-8). Median sleep efficiency (proportion of time in bed spent asleep): 89% (74-100%). ISI score correlated with sleep duration in 70%. Participants and nurses reported 100% device acceptability. Community (n=20): Sleep onset was delayed &gt;30 minutes in 25%. Median duration: 8 hours. Median awakenings per night: 3 (0-10). Median sleep efficiency: 91% (46-100). ISI score correlated with sleep duration in 90%. Participants and family reported 100% device acceptability. Conclusions: (1)A wireless monitor effectively measures sleep in cancer in both inpatient and community settings, (2) High acceptability supports clinical use, (3) Subjective sleep quality reports correlate with device, and (4) Further research: evaluate sleep improvement interventions with device.
Tolerance of bevacizumab in an older patient population: The Memorial Sloan-Kettering Cancer Center (MSKCC) experience
Authors: S. Richardson, M. N. Dickler, C. T. Dang, C. A. Hudis, T. A. Traina
Journal: Journal of Clinical Oncology (2008)

9569 Background: Bevacizumab (BEV) improves response and PFS when added to weekly paclitaxel in patients (pts) with metastatic breast cancer (MBC). Known toxicities include hypertension (HTN), thrombosis, bleeding and gastrointestinal perforation but the incidence of these events in older breast cancer pts is not well described. We conducted this retrospective review to describe the incidence of BEV-associated adverse events in pts ≥60 years of age with MBC. Methods: IRB approval was obtained to review medical records of all pts with MBC, age ≥60 years, treated with BEV in combination with chemotherapy at MSKCC between 1/2000- 6/2007. Eligible pts could not have received BEV on a clinical trial. Search of the Breast Cancer Medicine Service electronic medical record and pharmacy database identified eligible pts. Pt characteristics and incidence of NCI CTC v3 toxicities were calculated. These were compared to previous reports. Results: 40 pts met eligibility criteria. Median age = 66 (60–89). Median ECOG performance status = 1 (0- 1). 95% of pts had visceral disease. 65% of pts had ≥2 prior chemotherapy regimens for MBC. Chemotherapy concurrent with BEV: paclitaxel (12), docetaxel (5), capecitabine (5), vinorelbine (8), gemcitabine (5), other (5). Comorbidities: HTN 48%, coronary artery disease/CHF/arrhythmia 23%, venous thrombosis 15%, proteinuria 8%. Toxicity rates are shown in the Table. Grade 5 BEV-associated adverse events = 2. These older pts with MBC had more Grade 3/4 thrombosis, bleeding, perforation, fatigue and neutropenic fever than pts on historical randomized phase III trials of BEV+chemotherapy. Conclusion: BEV-based therapy may be more toxic in older patients but factors other than age may be important. BEV warrants prospective study in older pts and its pathophysiology should be explored further. In this population, the clinical benefits of BEV must be carefully weighed with the associated risks. S. Richardson support by NCI-Cancer Education Program Grant #R25 CA020449–30 NCI CTC v3 Bevacizumab-associated toxicity in an older breast cancer population BEV + Chemotherapy BEV + Capecitabine (Miller JCO) BEV + Paclitaxel (ECOG 2100) Grade 3/4 (%) Grade 5 (%) Grade 3/4 (%) Grade 3/4 (%) Hypertension 7.5 0 17.9 15 Proteinuria 5 0 0.9 2 Thrombosis/Embolism 10 2.5* 6.9 2 Perforation/Ulcer, GI 5 0 0 0 Hemorrhage 5 2.5** 0.4 2 LV dysfunction 0 0 3 0 Fatigue 10 0 7.4 8 Febrile neutropenia 2.5 0 0 0 * pulmonary embolism (docetaxel), ** gastrointestinal bleed (paclitaxel) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech Genentech Genentech Genentech
Neuroendocrine carcinoma in conjunction with Gleason score 8-10 prostate cancer: Clinical implications for patients treated with radiotherapy.
Authors: D. J. Krauss, M. Amin, S. Hayek, H. Ye, L. L. Kestin, F. Vicini, A. Martinez
Journal: Journal of Clinical Oncology (2010)

4649 Background: Neuroendocrine (NE) carcinoma cells may be associated with prostate cancer, more often in high grade tumors. Their significance in localized disease treated with radiotherapy (RT) remains uncertain. We conducted a clinicopathologic study to determine if RT patients with Gleason score 8-10 and a NE component are at risk for inferior outcomes vs. patients without NE features. Methods: Chromogranin (chromo) staining was attempted on core biopsies from 126 patients from the William Beaumont Hospital prostate cancer database. 99 had evaluable tumor in biopsy material. Patients received external beam RT alone or with high dose rate brachytherapy boost. Staining was quantified as 0%, < 1% (focal), 1-10%, or > 10% of tumor cells. Cox regression and Kaplan Meier estimates determined if the frequency of NE cells in core biopsy specimens correlated with clinical endpoints. Results: Median follow- up was 5.4 years. 27 patients had at least focal positive chromo staining. No significant differences existed between patients with or without staining in terms of age, pretreatment PSA, tumor stage, hormone therapy administration, % biopsy core involvement, or RT modality. Mean Gleason score was higher for the patients with absent chromo staining (8.4 vs. 8.2, p=0.04). Multivariate analysis showed chromo staining to adversely predict for PSA failure, distant metastases (DM), and cause-specific survival (CSS). At 10 years, DM rates were 13.1% for patients without and 51.3% for those with staining (p=0.005). CSS was 89.3% and 73.4%, respectively, for patients without and with chromo staining (p=0.001). Local recurrence was 7.3% without and 3.8% with chromo positivity (p=0.62). A trend toward an overall survival advantage was seen for patients without chromo staining with 5-year rates of 77.8% vs. 59.5% but 46.3% vs. 45.0% at 10 years (p=0.09). Results were similar when patients were grouped as < 1% vs. > 1% staining. Conclusions: For Gleason score 8-10 prostate cancer, the presence of NE carcinoma cells is associated with inferior clinical outcomes for patients treated with radiotherapy. This appears to relate most directly to an increase in distant as opposed to local failures. No significant financial relationships to disclose.
Trans-Pacific variation in outcomes for men treated with primary androgen deprivation therapy for localized prostate cancer.
Authors: Matthew R. Cooperberg, Shiro Hinotsu, Mikio Namiki, Peter Carroll, Hideyuki Akaza
Journal: Journal of Clinical Oncology (2013)

92 Background: Primary androgen deprivation therapy (PADT) is endorsed as an option for monotherapy for localized prostate cancer by guidelines in Asia but not in the United States (US) or Europe. PADT use is common, however, in both the US and Japan. Prior studies on either side of the Pacific have reported disparate outcomes for PADT; we aimed to explore these differences in a direct comparison study. Methods: Data were drawn from the US community-based CaPSURE registry and from J-CaP, comprising men in Japan treated with PADT. 1934 men treated with PADT were included from CaPSURE, and 16,300 treated in J-CaP. Risk adjustment was based on the validated Japan Cancer of the Prostate Risk Assessment (J-CAPRA) score. Cox proportional hazards regression was used to assess prostate cancer-specific mortality (CSM), adjusting for age, J-CAPRA, year of diagnosis, and treatment type (combined androgen blockade [CAB] vs. castration (medical or surgical) monotherapy). Results: Men treated with PADT in J-CaP were older than those in CaPSURE (mean age 75.0 vs. 72.7, p&lt;0.001), and had higher risk disease (mean J-CAPRA score 3.0 vs. 2.1, p&lt;0.001). They were more likely to be treated with CAB: 67.1% vs. 44.5% (p&lt;0.001). In the Cox model, the hazard ratio (HR) for PCSM was 0.31 for J-CaP compared to CaPSURE, 95% CI 0.25–0.40. In J-CaP, CAB improved survival compared to castration alone (HR 0.81, 95% CI 0.66–1.0), but this effect was not observed in CaPSURE (HR 0.96, 95% CI 0.69–1.34). For all-cause mortality, the HR for J-CaP was 0.27 (95% CI 0.24–0.30). Conclusions: Adjusting for multiple factors including disease risk and type of androgen ablation, men treated with PADT in Japan compared to the US have more than 3-fold lower CSM and 4-fold better overall survival. CAB improved outcomes compared to castration alone in J-CaP but not in CaPSURE. These findings support existing guidelines both encouraging PADT in Asia and discouraging its use in the West. The reasons for these substantial differences likely include both genetic and dietary/environmental factors, as well as potential confounding variables such as comorbidities. Such factors may explain varying biology of prostate cancer on both sides of the Pacific.