tbuckley/cabot-search huggingface dataset:
Should all antiemetic guidelines recommend adding a NK<sub>1</sub> receptor antagonist (NK<sub>1</sub>RA) in patients (pts) receiving carboplatin (carbo)? Efficacy evaluation of NEPA, a fixed combination of the NK<sub>1</sub>RA, netupitant, and palonosetron.
Authors: Karin Jordan, Richard J. Gralla, Giada Rizzi
Journal: Journal of Clinical Oncology (2015)

9597 Background: Controversy continues whether a NK1RA should be added to a 5HT3RA + dexamethasone (DEX) in pts receiving carbo, with inconsistent guideline recommendations by NCCN, ASCO, and MASCC/ESMO. It is routine to use a NK1RA for pts receiving cisplatin where a 12%-20% benefit is seen. A subset analysis in 192 pts receiving carbo in a 2009 randomized trial (Rapoport, Supp Care Cancer) indicated a 14% benefit in pts receiving a NK1RA as part of triple antiemetic therapy (no emesis rate: 84%, 95% CI 77-91% versus 70%, 95% CI 59-79% with 2 drugs, p < 0.02). Similar results were seen in other trials. We undertook this post-hoc subset analysis of pts receiving carbo as part of a NEPA Phase 3 trial to determine if NEPA would show a consistent complete response (CR: no emesis/rescue) rate and to examine nausea control. Methods: 196 chemotherapy-naïve pts randomized to NEPA + DEX (n = 145) or aprepitant (APR) + PALO + DEX (n = 51) received carbo in cycle 1. CR and no significant nausea (NSN: score ≤25 on 100mm visual analog scale) rates were calculated for all pts and by gender / age for NEPA pts over multiple cycles. Results: The overall (0-120h) CR rates for cycles 1-4 were similar for NEPA (80%, 91%, 92%, and 93%) and APR (82%, 88%, 88%, and 90%). Cycle 1-4 NSN rates were also similar (NEPA 84-96%; APR 82-90%). In the NEPA pts, 54% had lung cancer and 21% ovarian; cycle 1 overall CR rates were 77% / 77%, respectively. NEPA results by risk groups are in the Table. Conclusions: This subset analysis of pts receiving carbo shows consistent 5-day CR rates with an added NK1RA in this and historical studies; additionally, it documents high control rates of nausea with NEPA even in women and younger pts. Given the consistency of the control rates for added NK1RAs, as seen for NEPA and APR, guideline groups and practitioners should consider giving a NK1RA antiemetic triplet in pts receiving carbo. Clinical trial information: NCT01376297. Cycle 1 NEPA + DEX Overall 0-120h CR [95% CI] NSN All Pts (N = 145) 80% [73, 86] 84% [77, 89] Females (N = 66) 73% [61, 82] 88% [78, 94] Males (N = 79) 86% [76, 92] 81% [71, 88] < 55 years (N = 53) 85% [73, 92] 87% [75, 94] ≥ 55 years (N = 92) 77% [68, 85] 83% [74, 89]
EGFr dinucleotide repeat polymorphism in non-small cell lung cancer
Authors: S. Dubey, J. Miller, P. Stephenson, S. M. Keller, D. H. Johnson, J. H. Schiller, J. M. Kolesar
Journal: Journal of Clinical Oncology (2004)

9585 Background: Intron 1 of the epidermal growth factor receptor (EGFr) gene contains a polymorphic simple sequence repeat (SSR) of 14–21 CA dinucleotides, which regulates the transcription and expression of EGFr. In breast cancer, the length of these repeats is inversely related to EGFr expression. In breast and colorectal cancer, the most common genotype was heterozygous for 16 and 20 repeats. We evaluated the distribution of the (CA)n repeats in non-small cell lung cancer (NSCLC). Methods: Genomic DNA isolated from primary lung tumor and matched normal nodes samples from ECOG 3590 study were analyzed. Extracted DNA was amplified for EGFr intron1 by PCR and sequenced in a 3730XL DNA analyzer. Results: 157 primary tumors and 72 nodes were sequenced. 105 (67%) tumor samples were heterozygous for intron 1. There was no significant association between homozygous or heterozygous status with baseline characteristics such as race, gender, weight, performance status, histology, and stage or survival. The commonest genotype was heterozygous with allele lengths of 17/19 dinucleotides (17.8%), followed closely by 17/18 (11.4%) and homozygous 19 (11.4%) (Table1). SSR length of 18 or less dinucleotide repeats was associated with squamous cell histology (p=0.03). SSR length did not correlate with survival (p=0.20) . Conclusions: This is the first study to assess the EGFr SSR polymorphism in NSCLC. The commonest genotype for SSR length in NSCLC differs from breast and colon cancer. There is no significant correlation between allele status and length of the SSR with survival. Tumors with a shorter SSR were associated with squamous histology. No significant financial relationships to disclose.
Mycophenolate Mofetil Versus Placebo for Systemic Sclerosis–Related Interstitial Lung Disease: An Analysis of Scleroderma Lung Studies I and II
Authors: Elizabeth R. Volkmann, Donald P. Tashkin, Ning Li, Michael D. Roth, Dinesh Khanna, Anna‐Maria Hoffmann‐Vold, Grace Kim, Jonathan Goldin, Philip J. Clements, Daniel E. Furst, Robert M. Elashoff
Journal: Arthritis & Rheumatology (2017)

To compare mycophenolate mofetil (MMF) with placebo for the treatment of systemic sclerosis (SSc)-related interstitial lung disease (ILD).
High-dose dense chemotherapy with epirubicin and paclitaxel with peripheral blood progenitor cell support in women with high-risk stage II-IIIA breast cancer
Authors: G. Rosti, U. De Giorgi, G. L. Frassineti, G. Ciucci, L. Spinolo, E. Flamini, N. Giovannini, M. Monti, F. Zumaglini, M. Marangolo
Journal: Journal of Clinical Oncology (2004)

807 Background: There is persuasive clinical evidence that the chemotherapeutic efficacy in patients (pts) with breast cancer is related to the dose-intensity of the chemotherapy delivered. Methods: Fifty consecutive pts with stage II-IIIA breast cancer and 9 or more involved nodes (first 25 pts) or 4 or more (next 25 pts) received a mobilizing course consisting of epirubicin 150 mg/m2, preceded by dexrazoxane (day 1), paclitaxel 175 mg/m2 (day 2), plus filgrastim; followed by 3 courses of epirubicin 150 mg/m2, preceded by dexrazoxane (day 1), paclitaxel 400 mg/m2 (day 2), with peripheral blood progenitor cell support (PBPCS) and filgrastim, every 16–19 days. Paclitaxel 400 mg/m2 was given as 6-hour infusion in the first 25 pts (P6h pts), and as 24-hour infusion in the next 25 pts (P24h pts) in order to reduce neurotoxicity. Results: No toxic death occurred. Three pts went off study due to a severe hypersensitivity reaction to paclitaxel (1 P6h/2 P24h pts). Five pts interrupted the treatment due to prolonged grade 3 peripheral neurotoxicity (3 P6h/2 P24h pts). In all cases, neurotoxicity was reversible. Prospective evaluation of cardiotoxicity is ongoing; none of the pts developed clinically apparent congestive heart failure. In P6h pts, the disease-free and overall survival rates at 45-month follow-up were 54% and 71% respectively. Results in P24h pts are too early. Conclusions: High-dose dense chemotherapy with epirubicin and paclitaxel with PBPCS and filgrastim appears a feasible and safe approach in women with high-risk stage II-IIIA breast cancer. Long-term results are warranted to better define toxicity and activity of this regimen. This work was supported by Italian National Research Council (Project n°31412), and by a grant from Istituto Oncologico Romagnolo. No significant financial relationships to disclose.
A phase 2 trial of BMS-247550 (ixabepilone), an epothilone B analog, given daily x 5 in breast cancer
Authors: J. A. Low, S. B. Wedam, A. Brufsky, A. Berman, E. Croarkin, R. Parks, S. M. Steinberg, N. Mannan, T. Fojo, S. M. Swain
Journal: Journal of Clinical Oncology (2004)

545 Background: The epothilones are nontaxane microtubule stabilizers which have shown promising activity in 1- and 3-hour infusions every 3 weeks. Grade 3 neuropathy was reported in 12–37% of breast cancer patients. Methods: Patients with metastatic or locally advanced breast cancer and measurable disease were stratified by prior taxane therapy. Patients were treated with BMS-247550 at 6 mg/m2/d IV d1–5, every 3 weeks. A novel battery of tests to assess neurotoxicity included subjective questionnaires, balance testing, Semmes-Weinstein monofilaments, the Jebsen Test of Hand Function, the Grooved Peg Board Test, and nerve conduction studies. Results: Forty-two patients received 174 cycles. Prior taxane-treated patients received 0–10 (median 2) prior chemo regimens; taxane naïve patients received 0–1 (median 0) prior chemo regimens. Grade 3 and 4 toxicities per patient: neutropenia (32%, grade 4: 20%), febrile neutropenia (10%, all grade 3), thrombocytopenia (5%), fatigue (15%), diarrhea (12%), nausea/vomiting (5%), constipation (2%), myalgia/arthralgia (2%), sensory neuropathy (grade 3: 2%, all grades: 40%). Of the 33 prior taxane-treated patients, there are 6 (18%) PR, 12 (40%) SD, 12 (40%) PD, 3 (9%) too early to evaluate (TE). Of the 9 taxane-naive patients, 4 (44%) PR, 4 (44%) SD, and 1 (11%) TE. One patient was removed from study due to grade 3 neurotoxicity, and 2 pts for other grade 3/4 toxicities. Eleven of 30 (37%) patients with no baseline neuropathy developed grade 1; 3 (10%) of 30 developed grade 2; 1 (3%) developed grade 3. Only 1 of 12 (8%) patients with baseline grade 1 developed grade 2 neuropathy. Increased sensory neuropathy was associated with self-reported worsening of pain intensity (p<0.01), but not with the other neurotoxicity tests evaluated, and further analyses are ongoing. Eight patients have had pre- and post-treatment biopsies. Tubulin stabilization will be assessed by examining post-translational modifications of tubulin on pre- and post-therapy biopsies by Western blot. Conclusions: Responses are seen in both prior taxane-treated and taxane naïve patients. Sensory neuropathy was mild with grade 3 neurotoxicity rarely seen. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb
Mammography screening in France: Results of EDIFICE study
Authors: D. Serin, M. Namer, L. Cals, O. Rixe, C. Roussel, Y. Coscas, J. Blay, X. Pivot
Journal: Journal of Clinical Oncology (2006)

10701 Background: The EDIFICE study aimed to allow better understanding of population’s adhesion to the screening tests available for the 4 most frequent cancers: breast, colorectal, prostate and lung. Implementation of breast cancer screening (CS) was generalized since 2003 in France: women aged between 50 and 74 years are invited to do a mammography (M) every second year. Methods: This nationwide observational study was the first implemented in France (from January 18 th to February 2 nd , 2005) among a representative sample of 1504 subjects aged between 40 and 75 years including 773 women and a representative sample of 600 general practitioners (GPs). Information about participating subjects included socio-demographic characteristics, attitude towards CS and actual experience of CS, and about GPs’ medical practice regarding CS. Results: Among the 507 participating women (PW) aged between 50 and 74 years, 93% had done at least one M: 55% underwent this test on their own initiative and 45% of PW had it during a systematic screening plan. Most PW in the systematic screening (89%) had a M dating from less than 2 years vs 74% of the others (X 2 = 18.9; p &lt; 0,01). Main reasons for not performing the biennial screening test were: lack of care (18%), “it’s not a priority” (18%) and no advice from the GPs (15%). 79% of the PW had at least one M before 50 years (1 st test at the mean age of 37.9±6 years). Among the 600 GPs, 68% systematically recommended M to their patients. GPs’ perceptions of the reasons for women’s avoidance of screening test were their unwillingness to be aware of M results (44%) and their belief in painful symptoms related to M (52%). Conclusions: This first nationwide study has shown the high rate of PW’s attendance at M screening. It pointed out that systematic and organized screening played a major role in regularity of screening over 2 years, and GP is a key actor in heightening public awareness. No significant financial relationships to disclose.
Is age a risk factor of congestive heart failure (CHF) in patients receiving trastuzumab (H)? Results from two Belgian compassionate use programs in metastatic breast cancer (MBC) patients (pts)
Authors: R. Giuliani, A. M. Minisini, M. Paesmans, J. Y. Leroy, M. Reginster, J. Demol, J.-P. Kains, A. Di Leo, M. J. Piccart, L. Biganzoli
Journal: Journal of Clinical Oncology (2004)

838 Background: Age ≥60 years is considered among the possible risk factors of H related cardiac toxicity. Methods: Between 1/99 and 5/02 two compassionate use programs were run in Belgium to provide H to patients (pts) with HER2-overexpressing MBC. A total of 227 pts received at least one administration of weekly H, as single agent or in combination with chemotherapy, and were eligible for a retrospective analysis that aimed to evaluate the role of age as risk factor for H related CHF. Data on comorbidities (CO, i.e. hypertension, previous drugs-related cardiac toxicity, diabetes, hyperlipidemia), radiotherapy to left breast/chest wall, prior anthracyclines (A) cumulative dose, time interval from last A administration, cumulative dose and time on H were collected from medical files and analyzed as possible risk factors of CHF. Results: Pts median age was 53 years (range 22–82); 158 pts were < 60 years old and 69 were ≥60 years old (60+). In the latter group 25 pts were 70+. The two age groups differed in terms of presence of CO (higher in 60+) and administration of H, single agent vs combination regimens, (H alone > in 60+). None of the pts presented with an active CHF at the moment of the first H dose. CHF was reported in 8.9% (n=14), 7.2% (n=5) and 4% (n=1) of the patients aged <60, 60+, and 70+, respectively. The difference between the three age subgroups was not statistically significant. The presence of CO showed to be predictive of CHF, independently of the age cut-off (OR 9.22, 95% CI 3.4–24.97). Combining age with CO, i.e (a) age <60 and age 60+ and no CO vs (b) age 60+ and CO, (b) was associated to an odd ratio (OR)= 4.59 of CHF (95% CI 1.46–14.49, p=0.009). None of the other above-mentioned variables were found to be predictive of CHF. Conclusions: Preexisting morbidities rather than age were found to be associated to H related CHF. Fit elderly pts showed similar probability of developing CHF as younger pts and should not be denied this important treatment modality. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Hoffmann-La Roche Ltd. Hoffmann-La Roche Ltd. Hoffmann-La Roche Ltd.
Amifostine in the subcutaneous route –Is it feasible?
Authors: W. Buchsmann, J. Jabbari, B. Katsimbari, W. Wagner, G. Wiedemann
Journal: Journal of Clinical Oncology (2004)

5567 Background: There is some evidence indicating that subcutaneous route of amifostin is feasible and has the same efficiency than intravenous application in the daily routine . A lot of radiotherapists had met bad experiences and therefore we try to reproduce the above mentioned results. Methods: 37 Patients (16 females and 21 males) who had to be irradiated because of different kinds of cancers received amifostin subcutaneously at a dose of 500 mg daily one hour before radiation. Results: In 27 Patients there were trivial adverse effects but in 10 Patients we had documented severe adverse effects of Grade 3 and 4 according to the WHO Toxicity Score. The following side effects had been documented: Nausea 8x, vomiting 8x, hypotonus 5x, allergic reaction 1x, severe dyspnea 2x, upper abdominal pain 6x, erythema 2x, generalized urticaria 1x, vertigo 1x, loss of consciousness 1x. The time when the side effects appeared was completely different. In four patients it appeared between the 10th and 28th application; in six patients between the first and 6th application. Hence, there is no correlation between the number of injections and feasibility. Conclusions: Amifostin as a radioprotector in radiotherapy should not be given subcutaneously. In our investigation 27% of all patients had suffered side effects of Grade 3 or more according to the WHO Score. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Essex Chemie AG
Pelvic reconstruction using massive frozen autograft bearing tumor
Authors: H. Nishida, H. Tsuchiya, N. Yamamoto, T. Shirai, M. Karita, M. Hayashi, K. Tomita
Journal: Journal of Clinical Oncology (2004)

9040 Background: Allograft is difficult to obtain in Japan for socioreligious reasons, so autograft bone, such as irradiation, autoclaving and pasteurization et al, has been widely used. However, they may cause weakness of the treated bone and loss of bone induction activity. So we developed a new method for treating autografts that utilizes the hypothermic effect of liquid nitrogen, especially reconstruction after the resection of illiosacral joint or periacetabulum, based on the results of in vitro and in vivo studies. Methods: Six patients with pelvic malignant bone tumors (2 chondrosarcomas, 1 osteosarcoma, 1 Ewing sarcoma and 2 metastatic tumors) were treated with this method. All these tumors invaded illiosacral joint or periacetabulum, the type of resection were P14P4, P14, P123, P124, P2and P12P12 according to Enneking's classification. After tumor excision, the tumor and surrounding soft tissue were removed, and the specimen was immediately frozen in liquid nitrogen for 20 minutes. Later, the specimen was gradually thawed at room temperature and in distilled water. Finally reconstructed with liquid nitrogen autograft, osteosynthesis with suitable internal fixation. Results: With a mean follow-up of 18 months, union of host-graft junction was observed in 6 patients in 5.5 months after surgery, and the reconstruction of pelvic ring was complete in 5 patients. Osteoarticular reconstruction was performed perfectly for 6 patients. Excellent function was found in 3 patients, good in one, fair in one and poor in one. As for complications, there were two deep infections, frozen autograft was removed in one patient, the other patient was given debridement and the infection subsided eventually. Bone absorption and fracture were not found. One local recurrence arised from residual soft tissue. Three patients were still free of disease and three had died of metastatic disease. Conclusions: This biological reconstruction is considered to be a new and promising option in pelvic and sacral tumor, because it can provide perfect matching and immediate stability. No significant financial relationships to disclose.
Survival results and prognostic factors in T4 N0-3 non-small cell lung cancer patients according to the AJCC 7th edition staging system.
Authors: Deniz Arslan, Hakan Sat Bozcuk, Ali Murat Tatli, Seyda Gunduz, Mukremin Uysal, Sema Sezgin Goksu, Lokman Koral, Hasan Senol Coskun, Burhan Savas
Journal: Journal of Clinical Oncology (2013)

e18517 Background: In our study, we evaluated the survival results and prognostic factors among T4 local advanced non-small cell lung cancer (LA-NSCLC) patients in a large heterogeneous group, in accordance with the new staging system. Methods: We retrospectively evaluated the files of LA-NSCLC patients who have been treated at two centers between November 2003 and June 2012. One hundred twenty two T4 N0-3 M0 LA-NSCLC patients, identified according to the new staging system, were included in the study. Results: Median OS was 18.3 months, 1 year overall survival (OS) rate was 72%, 5 year OS rate was 28%. The median follow-up period was 17.4 months. Statistically significant predictors of survival were (p&lt;0.20) ECOG-PS, age, subgroups of T4 factor, stage and primary treatment in OS univariate analysis. It was found that the statistically significant variables in multivariate analysis of OS rate were ECOG-PS (p=0.001), diagnostic stage (p=0.021), and primary treatment (p=0.004). In the group given non-curative treatment, the median OS was 11.0 months, 19.0 months in the definitive RT group as for 26.6 months in the curative treatment group. While there was a significant difference between the non-curative group and the groups which had definitive RT and curative operations (respectively p&lt;0.001 and P=0.001) in terms of OS, no statistically significant difference (p=0.22) was found between the groups which had definitive RT and curative operations. Median EFS rate was 9.9 months, 46% in 1 year EFS rate, 19% in 3 years and 15% in 5 years. In univariate analysis of EFS rate with ECOG-PS, weight loss and staging, statistical significances were found only in PET-CT use, stage and primary treatment (p&lt;0.20). In multivariate analysis with EFS, only the primary treatment was statistically significant (p=0.001). In the group that was approached with non-curative treatment, the median EFS was 10.5 months and in the curative operation group it was 14.7 months. Conclusions: Independent prognostic factors among this heterogeneous group of T4 N0-3 M0 122 LA-NSCLC patients were diagnosis age, ECOG-PS, stage and primary treatment. Primary treatment was a significant prognostic indicator of EFS rate.
Clinical implication of mass-spectrometry-based selected reaction monitoring (SRM) assay in non-small cell lung cancer (NSCLC) patients exhibiting ALK gene rearrangement.
Authors: Ho Jung An, Eunkyung An, Wei-Li Liao, Jin Hyoung Kang, Jon Burrows, Todd A. Hembrough, Tae-Jung Kim
Journal: Journal of Clinical Oncology (2015)

e22145 Background: FISH is considered as a standard diagnostic method in detection of ALK gene rearrangement, but clinical response of crizotinib (ALK/Met inhibitor) was various in ALK FISH (+) patients. A newly developed mass spectrometry based SRM assay can detect and quantify tumor-specific ALK, Met, and other multiple druggable proteins at a same time. We evaluated the assay in NSCLC patients with ALK FISH positivity. Methods: 22 NSCLC patients with ALK FISH borderline (10-20%) to positive (20-55%) with various ALK IHC expressions (0 to 3) were selected. By using SRM assay, tumor-specific ALK protein, Met protein, and other protein markers for chemotherapeutic agents were quantified in formalin fixed, paraffin-embedded tumor tissues. ALK status was compared with clinical outcome in crizotinib-treated patients and protein levels of chemotherapeutic markers were compared with outcomes in patients who had received chemotherapy. Results: Of the 22 ALK-positive cases by FISH (8 borderline and 14 positive ALK rearranged cases), only 4 cases (18%) were ALK-positive by all three methods. 17 (77%) had no detectable ALK protein by IHC or SRM. One ALK IHC (+) FISH (+) SRM (-) case revealed to have ALK kinase frame shift. Of 7 crizotinib-treated NSCLC patients, a single patient with CR had detectable levels of both ALK and MET; three of 4 patients with PR had tumors expressing either ALK or MET protein. No crizotinib targets were found in the 2 patients with PD nor in 1 patient with PR to crizotinib. Among ten patients who received chemotherapy other than crizotinib, outcomes were PR (n = 7) and PD (n = 3). ERCC1, XRCC1, and RRM1 for platinum-based chemotherapy; FR alpha for pemetrexed; hENT1 for gemcitabine; and TUBB3 and SPARC for taxane indicate a good predictive value for these markers for chemotherapy response. Conclusions: For ALK borderline or positive rearranged patients, SRM quantification of ALK and Met protein levels may help to predict crizotinib responses. Multiplexed mass spectrometry based proteomic screening is useful on therapeutic decision-making in NCSLC.