tbuckley/cabot-search huggingface dataset:
Incidence and severity of sensory neuropathy (SN) with bevacizumab (B) added to dose-dense (dd) doxorubicin/cyclophosphamide (AC) followed by nanoparticle albumin-bound (nab) paclitaxel (P) in patients (pts) with early stage breast cancer (BC)
Authors: M. R. Sierecki, H. S. Rugo, H. L. McArthur, T. A. Traina, M. Paulson, M. Rourke, L. Norton, A. D. Seidman, C. A. Hudis, M. N. Dickler
Journal: Journal of Clinical Oncology (2008)

589 Background: DD q2week (wk) AC-P is superior to q3wk AC-P (Citron, JCO 2003). In metastatic BC (MBC), q3wk nab-P is more active than q3wk P (Gradishar, JCO 2005), and B improves PFS when added to wkly P (E2100, Miller, NEJM 2007). AC-P + B is currently under phase III study as adjuvant therapy (E5103), and nab-P may offer superior efficacy to P in this setting. However, grade (gr) 3 SN was greater with q3wk nab-P (260 mg/m2) than P (175 mg/m2) (10% vs 2%) in MBC and B may increase SN of P (E2100). Without B, ddAC-nab-P caused 2–14% gr 3 SN (Burstein, ASCO 2007; Robert, SABCS 2005). We assessed the incidence and severity of SN over time in pts treated on a pilot trial of adjuvant B + ddAC-nab-P. Methods: Eligible pts had resected HER2(-) BC. 80 pts enrolled and received B (10mg/kg IV q 2wks x 8 cycles) concurrent with chemoRx (AC 60/600 mg/m2 x 4, followed by nab-P 260 mg/m2 x 4). B continued at 15mg/kg IV q3wks x 12. Pegfilgrastim was given day 2 after each chemoRx. Radiation and endocrine Rx were administered per standard of care. Pts were evaluated for toxicity q2wks during chemoRx and q6wks during B alone. Dose reduction of 20% was planned for ≥ gr3 SN. Results: As of 12/1/07, 80 pts received a median of 14 cycles (range 1–21); to date, 79 completed B + AC, 72 completed B + AC-nab-P, 22 completed B, and 36 are still receiving study Rx. 65 pts (81%) had SN at any time during Rx: gr1 38%, gr2 28%, gr3 15%. Peak incidence of SN of any grade was post B + nab-P #4 (wk 16): 46/80 (58%); gr1 41%, gr2 14%, gr3 2.5%. 4 pts developed gr3 SN after only 1 cycle of B + nab-P, leading 2 pts to stop study Rx. By wk 28 (14 wks after B + nab-P #4), gr2 and 3 SN was improved in 11 and 7 pts, respectively. Conclusions: The rate of gr3 SN with B + ddAC-nabP is similar to studies of ddAC-nab-P without B. By wk 28, the majority of pts recovered to ≤ gr1. Updated results will be reported. Incidence of Sensory Neuropathy at Follow-up Visits (N) Grade Post B+AC4 N=79 Post B+nabP1 N=78 Post B+nabP2 N=76 Post B+nabP3 N=74 Post B+nabP4 N=72 B Wk22 N=67 B Wk28 N=60 B Wk34 N=48 B Wk40 N=42 0 66 42 42 32 26 35 34 30 23 1 11 28 26 29 33 17 20 14 15 2 2 4 7 12 11 13 4 2 3 3 0 4 1 1 2 2 2 2 1 4 0 0 0 0 0 0 0 0 0 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Abraxis, Genentech™ BioOncology Abraxis, Genentech™ BioOncology Abraxis, Genentech™ BioOncology
Effects of diagnostic method and surgery on safety of first-line bevacizumab plus chemotherapy in advanced or recurrent non-squamous non-small cell lung cancer (NSCLC): MO19390 (SAiL)
Authors: C. Tsai, N. Thatcher
Journal: Journal of Clinical Oncology (2008)

8058 Background: Safety data from the ongoing study of first-line bevacizumab (Bev) plus chemotherapy in patients (pts) with NSCLC (SAiL; MO19390) were analyzed to assess if the bleeding risk was affected by surgical procedure or diagnostic method. The latter, as a cytology-based diagnosis of NSCLC, may not reliably exclude squamous-cell type tumors. Methods: Pts with histologically and/or cytologically documented, locally advanced, metastatic non-squamous NSCLC and an ECOG PS of 0–2 receive open-label Bev plus standard first-line chemotherapy for up to 6 cycles followed by Bev alone until disease progression or unacceptable toxicity. Pts with a history of hemoptysis or evidence of either tumor invading major blood vessels or CNS mets are excluded (no baseline CNS scans). Results: Here we present preliminary data as documented in the EDC system (November 2007). 1065 pts (median age 60 years) have completed at least one cycle of treatment and are evaluable for safety. Diagnosis by cytology was not associated with higher bleeding risk (Table 1A). Incidence of bleeding complications in 190 pts who underwent surgery before and/or during the study was not increased compared with 875 without surgery (Table 1B). Only 4 pts undergoing surgery reported impaired healing or wound complication. Table 1A. Bleeding events by cytology/histology CTC ≥ grade 3/grade 5; B. Bleeding events for pts with/without surgery CTC ≥ grade 3/grade 5. Conclusions: This analysis suggests that there is no increased bleeding risk to date for pts diagnosed by cytology versus histology for Bev based therapy until progression and no increased risk associated with surgical procedures. The incidence of impaired wound healing was low. Updated results will be discussed. Table 1A Adverse event (≥ grade 3/ grade 5) Diagnostic method Cytology (n=309) Histology (n=608) Cytology + histology (n=99) Missing (n=49) n % n % n % n % Epistaxis 1/0 0.3/0 4/0 0.7/0 1/0 1.0/0 0/0 0/0 Hemoptysis 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 Other hemorrhage 1/1 0.3/0.3 3/0 0.5/0 3/1 3.0/1.0 0/0 0/0 Adverse event (≥ grade 3/ grade 5) Surgery before and/or during study (n=190) No surgery (n=875) n % n % Epistaxis 3/0 1.6/0 3/0 0.3/0 Hemoptysis 0/0 0/0 0/0 0/0 Other hemorrhage 3/0 1.6/0 4/2 0.5/0.2 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen, Roche, sanofi-aventis Roche Amgen, Roche, sanofi-aventis
A meta-analysis of randomized controlled trials comparing gemcitabine (GEM)-based combination chemotherapy with gemcitabine alone in advanced pancreatic cancer: An updated subgroup analysis of overall survival
Authors: Q. Yang, D. R. Xie, H. L. Liang, Z. M. Jiang, Z. F. Bi, S. L. Chen
Journal: Journal of Clinical Oncology (2008)

15661 Background: Previous meta-analyses (2005 ASCO Annual Meeting, Abst 4110; WJG, 2006) had shown that GEM-based combination improved overall survival in patients with advanced pancreatic cancer (APCa) as compared with GEM alone, but the role of GEM- based combination was still controversial. We therefore performed a subgroup analysis to seek the exactly effective GEM-based combination which would benefit patients with APCa. Methods: MEDLINE and EMBASE searches were supplemented by information from trial registers. We conducted Subgroup meta-analyses of randomized controlled trials for GEM-based combination and GEM alone in patients with APCa (1996–2007). The endpoint of the analyses was 6 or 12 months overall survival rate (6-mo OS/12-mo OS). Results: 27 studies comparing Gem-based combination with Gem alone were included in total. At last, 18 trials including 3881 patients were enrolled and divided into 5 subgroups, which were listed as follows: Subgroup 1-GEM plus cisplatin vs. GEM; Subgroup 2-GEM plus 5-fluorouracil vs. GEM; Subgroup 3- GEM plus irinotecan vs. GEM; Subgroup 4-GEM plus oxaliplatin vs. GEM; Subgroup 5-GEM plus capecitabine with GEM. The remaining 9 trials could not be classified to these 5 subgroups. There was no statistic difference in overall survival rate of Subgroup 1 (6-mo OS: Risk Difference [RD]=5%, p=0.24; 12-mo OS:RD=7%, p=0.37), Subgroup 2 (6-mo OS:RD=2%, p=0.46; 12-mo OS:RD=4%, p=0.19) and Subgroup 3 (6-mo OS:RD=-1%, p=0.88; 12-mo OS:RD=0%, p=0.97). For the analysis of Subgroup 4, GEM plus oxaliplatin improved 6-mo OS significantly (RD=11%, p=0.0007) and 12-mo OS probably (RD=5%, p=0.06). Similarly, for the analysis of Subgroup 5, GEM plus capecitabine improved 6-mo OS significantly (RD=7%, P=0.03) and 12-mo OS probably (RD=5%, P=0.08). Conclusion: These subgroup analyses of the available evidence suggested that GEM plus oxaliplatin and GEM plus capecitabine might be promising regimens as the front-line chemotherapy for patients with APCa, which encouraged further studies. No significant financial relationships to disclose.
Response to androgen signaling (AS)-directed therapy after treatment with abiraterone acetate (AA) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Post hoc analysis of study COU-AA-302.
Authors: Matthew R. Smith, Shannon Matheny, Fred Saad, Dana E. Rathkopf, Peter F.A. Mulders, Johann Sebastian De Bono, Eric Jay Small, Neal D. Shore, Karim Fizazi, Thian San Kheoh, Jinhui Li, Mary Beth Todd, Thomas W. Griffin, Margaret K. Yu, Charles J. Ryan
Journal: Journal of Clinical Oncology (2014)

21 Background: In study COU-AA-302 of men with mCRPC and no prior chemotherapy, AA plus prednisone (hereafter AA) significantly increased radiographic progression-free survival. There is limited information about response to subsequent AS-directed therapies following AA. In this post hoc analysis of pts who received AA during study COU-AA-302, we evaluated clinical response to subsequent AA or enzalutamide (ENZ). Methods: In COU-AA-302, 546 pts were randomized and received AA. Subsequent response and discontinuation data from 88 pts receiving AS-directed therapy after study were collected retrospectively, source verified, and entered into the database. Median time to prostate-specific antigen (PSA) progression with 95% confidence intervals was estimated using the Kaplan-Meier method. Results: As of May 2013, following AA on study, 55 pts received subsequent AA and 33 received subsequent ENZ. 69% (38/55) of pts in the AA then AA group and 67% (22/33) pts in the AA then ENZ group received intervening chemotherapy. Baseline patient characteristics were similar across both groups and to the overall COU-AA-302 population. Median (range) exposure to subsequent therapy was 4 (1-20) months for AA and 5 (1-12) months for ENZ. Response to subsequent AA or ENZ is summarized in the Table. Conclusions: In this post hoc analysis, pts previously treated with AA experienced modest clinical response on subsequent treatment with either AA or ENZ. These data support further studies of subsequent AS-targeted drugs following treatment with AA for mCRPC. Clinical trial information: NCT00887198. [Table: see text]
Phase III results of adjuvant radiotherapy (RT) versus wait-and-see (WS) in patients with pT3 prostate cancer following radical prostatectomy (RP)(ARO 96-02/AUO AP 09/95): Ten years follow-up.
Authors: Thomas Wiegel, Dirk Bottke, Detlef Bartkowiak, Claudia Bronner, Ursula Steiner, Alessandra Siegmann, Reinhard Golz, Stephan Störkel, Normann Willich, Axel Semjonow, Michael Stöckle, Christian Rübe, Peter Althaus, Udo Rebmann, Tilman Kälble, Horst J Feldmann, Manfred Wirth, Axel Hinke, Wolfgang Hinkelbein, Kurt Miller
Journal: Journal of Clinical Oncology (2013)

4 Background: Adjuvant RT for pT3 R1 or R0 patients (pts.) after RP remains controversial. The EORTC-phase-III- study suggested a 20% better biochemical control (bNED) after 10 years for RT but no survival advantage. In contrast, the SWOG trial stated not only a gain in bNED but also an improved metastasis free and overall survival after 12 years follow-up. Now, 10-years results from the ARO 96-02 study are available, which are based on the most precisely defined cohort among the three trials. Methods: 385 men with prostate cancer were randomized to either 60 Gy RT (arm A; n=193) or WS (arm B; n=192) before achieving an undetectable PSA. Pts. were stratified for Gleason-score, margin status, neoadjuvant hormonal treatment and stage (pT3a+b vs. c). When the undetectable PSA-level after RP was not achieved, progressive disease was stated and the pts. left arm A/B. Data analysis was by intent-to-treat (ITT). PSA-progression for pts. with undetectable post-RP PSA was defined as two consecutive increasing PSA. The primary endpoint was bNED. The study was powered to demonstrate a 15% increase in bNED for RT. Results: 78 pts. (20%) did not achieve an undetectable PSA and were stated as progressive disease (arm A: 45 pts., arm B: 33 pts.). Additionally, 34 pts. (23%) from the RT-arm did not receive RT. Therefore, 114 pts. had RT (arm A) and 159 pts. WS (arm B). Median follow up was 111.3 months for arm A and 113.3 months for arm B . bNED at 10 years increased to 56% for arm A (RT) compared with 35% for arm B (WS) (hazard ratio= 0.51; p = 0.00002. Out of 307 ITT pts., 15 died from prostate cancer, 23 for other and 5 for unknown reasons. There was no significant profit from ART regarding the endpoints metastasis-free survival (p=0.56) or overall survival (p=0.59). Worst late side effects to the rectum were two grade 2 cases after ART. Grade ≥2 bladder toxicity occurred in 4 out of 148 ITT pts. No grade 4 events were reported. Conclusions: With only one grade 3 case of late toxicity, ART was safe in pT3 prostate cancer. At 10 years median follow up, it reduced the risk of bNED by 49%. The study was not powered to detect differences in OS. Clinical trial information: ARO 96-02/AUO AP 09/95.
Survival benefits of adjuvant radiotherapy and lymph node dissection in pancreatic cancer treated with surgery and chemotherapy.
Authors: Eric Albert Mellon, Gregory M. Springett, Sarah E. Hoffe, Pamela Joy Hodul, Mokenge Peter Malafa, Kenneth Meredith, William J. Fulp, Xiuhua Zhao, Jill Weber, Ravi Shridhar
Journal: Journal of Clinical Oncology (2014)

263 Background: Prior SEER analyses of the benefit of radiotherapy in surgically resected pancreatic cancer could not analyze chemotherapy recipients due to limited database information. Recent updates permit us to determine the effects of postoperative radiation therapy (PORT) and lymph node resection (LNR) on overall survival (OS) in pancreatic cancer among patients treated with both surgery and chemotherapy. Methods: An analysis of surgically resected pancreatic cancer patients receiving chemotherapy from the SEER database between 2004-2008 was performed. Survival was calculated by Kaplan-Meier method and log-rank analysis. Multivariate analysis (MVA) was by the Cox proportional hazard model. Results: We identified 2,966 patients who met inclusion criteria. PORT significantly improved OS in pancreatic cancer patients treated with surgery and chemotherapy (p=0.02). Median survival (MS), 1-year OS, and 3-year OS was 21 months, 77%, and 28% with PORT (n=1842) versus 20 months, 70%, and 25% without radiation (n=1124). On subset analysis, the benefit of PORT was limited to node positive patients. In N1 patients (n=2043) MS, 1-year OS, and 3-year OS was 19 months, 73%, and 25% with PORT versus 18 months, 67%, and 20% without PORT (p&lt;0.01). For N0 patients (n=923) MS, 1-year OS, and 3-year OS was 26 months, 85%, and 36% with PORT versus 25 months, 79%, and 38% without PORT (p=0.87). Increasing nodal count on LNR correlated with improved OS on MVA for all and N1 patients (each p&lt;0.001). Significant cut points for OS based on LNR in N1 patients were found for greater than 8, 10, 12, 15, 20, and 30 nodes resected (p&lt;0.05 for all). Prognostic factors on MVA include receipt of radiation, age, female sex, well differentiated grade, N0 status, and disease contained within the pancreas (p &lt; 0.03 for all). In N1 patients (n=2043), these factors remained significant except patient age. In N0 patients (n=923), only pancreas-confined disease and less than high grade tumor were associated with survival benefit. Conclusions: PORT and degree of LNR are both correlated with improved OS in pancreatic cancer patients treated with surgery and chemotherapy. Benefit of PORT and LNR seems limited to node positive patients.
Morbidity and mortality after surgical treatment of screening detected lung cancer
Authors: G. Veronesi, L. Spaggiari, L. Preda, P. Maisonneuve, P. Scanagatta, F. Leo, P. Solli, N. Rotmentz, G. Pelosi, M. Bellomi
Journal: Journal of Clinical Oncology (2008)

7531 Background: One limit to the diffusion of lung cancer CT screening is the fear of serious or lethal postoperative complications (3% postoperative mortality after standard lobectomy in USA) in asymptomatic individuals with potentially slow growing malignancies. We report the results of surgical treatment of screening detected lung cancer in our single centre study. Methods: A prospective observational study using low dose CT for lung cancer screening started in 2004 in asymptomatic high-risk individuals. A non- invasive diagnostic protocol was applied to patients with nodules larger or equal to 5 mm. Patients with suspicious nodules were candidates to minimally invasive wedge resection, intraoperative frozen section and anatomical resection with radical lymph node dissection through lateral muscle sparing thoracotomy. Since 2007, lobectomy was performed with minimally-invasive robotic approach with radioguided localization of non-palpable lesions. Results: During the first three years of study, lung cancer was diagnosed in 128 (2.4%) out of the 5,201 enrolled volunteers. 98 tumors (77%) were prevalent and 30 (23%) incident. The mean size of the tumor detected at baseline CT screening was 15mm and decreased to 10mm and 9mm for tumors detected after the first and second annual CT screening. Conversely, the proportion of pathologic stage IA cancers increased from 50% ( 28/56) for tumors detected at baseline CT to 59% (21/37) and 80% (27/35) after first and second annual CT screening. 114 (89%) patients underwent resection while 14 had non-resectable cancers. Two patients (1.5%) underwent pneumonectomy, 85 (66%) traditional lobectomy, 15 (12%) robotic lobectomy and 12 (9.4%) a sublobar resection. The mean postoperative hospital stay was 7 days (range 3–24). Twenty-nine patients (25%) developed a complication, 8 (6%) of them were serious and 3 re-required a re operation (2%). None of the patients died within 30 days of intervention. In addition 21 patients had benign disease with no postoperative complications or mortality and a mean postoperative stay of 4.5 days. Conclusions: Surgical resection of screening detected lung cancers is associated with low postoperative morbidity and mortality. These results represent additional elements in support to CT screening of lung cancer. No significant financial relationships to disclose.
A supervised risk predictor of breast cancer based on biological subtypes
Authors: J. Parker, M. Mullins, M. C. Cheang, S. Davies, E. Mardis, T. O. Nielsen, M. J. Ellis, S. Marron, C. M. Perou, P. S. Bernard
Journal: Journal of Clinical Oncology (2008)

11008 Background: The biological subtypes of breast cancer designated as Luminal A (LumA), Luminal B (LumB), HER2, and Basal have shown prognostic significance. However, risk predictors based on these gene expression profiles have been difficult to clinically implement. Recognizing that there is a continuum in both the spectrum of breast cancer disease and the risk of survival, we sought to develop a supervised risk classier within the context of biological subtypes of breast cancer. Methods: Microarray and real-time quantitative RT-PCR data from 189 samples, procured as fresh frozen and formalin-fixed paraffin-embedded tissues, were used to statistically select prototypes for the biological subtypes of breast cancer. Classification algorithms were developed using 4 independent breast microarray studies consisting of 1,244 cases. A final test set prediction was done using real-time quantitative RT-PCR data generated on a cohort of 279 breast cancers archived for a median of 20.1 years. Results: The biological subtypes predicted on the combined training set showed prognostic significance in all stages of disease (1,244 subjects; p=7.1e-14), node negative disease with no adjuvant systemic therapy (733 subjects; p=6.2e-7), and in patients treated with endocrine therapy (404 subjects; p=1.3e-3). Basal tumors identified using the 50-gene breast classifier had a more complete response to chemotherapy as compared to the same cohort scored as triple negatives. An additional cohort of 279 heterogeneously treated samples was collected from formalin fixed paraffin embedded tissue. Our risk predictor based on distance to subtype centroids provided additional prognostic information and has a linear relationship to prognosis across diverse cohorts. Conclusions: We present an objective method to predict subtypes of breast cancer and generate a continuous risk score based on biological subtypes. The standardized assay can be performed on archived tissue blocks using real-time qRT-PCR, allowing retrospective cohorts and clinical samples to be tested within the framework of specimen processing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Universtiy Genomics
A decision analysis on the balance between cancer survival and cisplatin ototoxicity in children with germ cell tumors
Authors: Y. Li, R. B. Womer, J. H. Silber
Journal: Journal of Clinical Oncology (2005)

8502 Background: Parents and childhood cancer survivors were asked to judge whether an increased survival rate in high-dose cisplatin chemotherapy for germ cell tumors was worth the increased risk of permanent hearing loss. Methods: A decision model was constructed to closely reflect the therapeutic choices faced by families with children diagnosed with a germ cell tumor. Based on the CCG treatment protocols 8882 and 8891, the model includes different dose schedules of cisplatin, their associated event-free-survival rates and the corresponding varying degrees of hearing loss. Also included were adverse events such as relapse, salvage therapies, and the resulting additional hearing loss from salvage therapy. Respondents assigned Standard Gamble (SG) preference weights to three outcomes vignettes of surviving cancer with mild, moderate, and moderately severe high-frequency sensorineural hearing loss. The solutions of the decision model were obtained according to the SG scores of 31 parents of childhood cancer survivors and 17 children survivors themselves. Results: The model showed that 28 out of the 31 parents tested (90%) would recommend the high-dose regimen, while 10 out of the 17 childhood survivors tested (59%, p < 0.01) suggested high-dose cisplatin. Parents considered cancer survival with sensorineural hearing loss perfectly manageable and not worth the risk of death (average SG utility 0.96), while children who survived cancer deemed such outcomes significantly detrimental and were willing to take a risk of death in order to mitigate the possibility of permanent hearing loss (average SG utility = 0.92, significantly different from parents’, p < 0.05). The differences were not affected by the respondents’ numeracy and/or omission bias. Conclusions: As childhood cancer survivors enter adulthood and start taking charge of their own treatment decisions, some would retrospectively make different treatment decisions than did their parents. Findings derived from decision analysis methods may help researchers better understand the complex ethical and emotional issues surrounding therapeutic decisions in childhood cancer, and may help promote a better decision-making process. No significant financial relationships to disclose.
Reply to Freyschlag et al
Authors: Jeffrey S. Wefel, Kyle R. Noll, Ganesh Rao, Daniel P. Cahill
Journal: Neuro-Oncology (2017)

Causal research on the origin of NCF impairments is cumbersome and has not yet yielded clear results.Most likely NCF impairment is due to infiltrative behavior of the tumors into subcortical networks, 7 as this has been demonstrated in diffuse infiltrating low-grade gliomas.With these limitations of current research, the cause of NCF impairments remains largely unclear.The effect of IDH mutational status on NCF is therefore still a matter of debate, as confounding factors like age may play an important role.We congratulate the authors for their commitment to this crucial topic in the care of patients with gliomas.