tbuckley/cabot-search huggingface dataset:
A new method for partial breast reconstruction: 3-year New Zealand experience.
Authors: Stan Govender, John Harman, Gail Lebovic, John Simpson, Benji Benjamin
Journal: Journal of Clinical Oncology (2015)

89 Background: Most women in New Zealand undergo partial mastectomy (PM) and 6 weeks of whole breast irradiation for early breast cancer. Oncoplastic surgery (OPS) is common, however, reconstruction of the breast during partial mastectomy presents challenges for radiation targeting since tissues have been extensively rearranged. Further complicating matters, the seroma cavity is often absent, and many patients travel to different cities for radiation without much communication between the surgeon and radiation oncologist prior to treatment. Throughout the country there is interest in promoting hypofractionated or accelerated radiotherapy, however, these techniques cannot be popularized without accurate targeting to minimize complications. In this series of patients we studied a new method of breast reconstruction using a bioabsorbable implant that serves as a surgical site marker as well. Methods: Following informed consent, 15 women were studied in a prospective manner. The bioabsorbable implant was sutured into the tumor resection site, and tissue flaps were directly attached. Radiation treatment protocols followed ASTRO guidelines. Results: The implant provided volume replacement and acted as a scaffolding for the breast tissue flaps providing local reconstruction. Cosmetic outcomes were excellent in all patients, no device related or radiation complications occurred. One patient had a post-operative hematoma that resolved without intervention, there were no post-operative infections. 3 year follow up shows no tumor recurrences, and no untoward effects. When compared to conventional radiation targeting, use of the implant showed a &gt; 50% reduction in treatment volume is possible. 3 year mammograms show normal regrowth of tissue without artifact and with minimal fibrosis. Conclusions: Three year follow-up shows this "mini" breast implant assists with oncoplastic breast reconstruction, while at the same time clearly marks the surgical site of tumor excision. Patients tolerated it well, and radiotherapy planning, positioning and treatment were all facilitated by the implant. Excellent patient outcomes in this pilot study have resulted in a national evaluation of this method in the public healthcare sector.
Adjuvant chemotherapy (AC) in stage IB non-small cell lung cancer (NSCLC): Long-term follow-up of Cancer and Leukemia Group B (CALGB) 9633.
Authors: G. M. Strauss, X. F. Wang, M. Maddaus, D. Johnstone, E. Johnson, D. Harpole, H. H. Gillenwater, L. Gu, D. Sugarbaker, M. R. Green, S. L. Graziano, R. A. Kratzke, R. L. Schilsky, J. Crawford, E. E. Vokes
Journal: Journal of Clinical Oncology (2011)

7015 Background: The value of AC in stage IB NSCLC remains controversial. In 2004, preliminary results of CALGB 9633 demonstrated a statistically significant overall survival (OS) advantage for pts randomized to adjuvant paclitaxel and carboplatin in resected stage IB NSCLC. However, subsequent analyses failed to demonstrate a significant OS advantage for all pts, although an unplanned subset analysis did show improved OS in pts with tumor diameter ≥4 cm (JCO, 26:5043, 2008). This report provides updated OS for CALGB 9633. Moreover, because the new 2010 AJCC staging system does not recognize 4 cm as a cut point, we correlated results with subgroups incorporated in the new system. Methods: Resected stage IB pts were randomized to paclitaxel 200 mg/m2 and carboplatin AUC 6 q3wks X4 cycles or observation. OS was the primary endpoint. Because of slow accrual, the accrual target was reduced from 500 to 384 pts, providing 80% power using a 1-tail logrank with alpha=0.05. Results: Between 1996-2003, 344 pts were randomized. Median follow-up is 9 yrs. There are now 197 deaths. While the study remains negative, there is a powerful trend toward improved OS for all pts (HR=0.80; 90% CI 0.63-1.02; p=0.062, 1-tail), with a 7% advantage in 8 yr OS favoring AC (51% vs. 44%; p=0.087); median OS is 8.2/6.6 yrs in chemo/control groups. Subgroup analysis using a 4 cm cut-off continues to show a strong OS signal favoring AC for those with large tumors. In pts with tumors ≥4 cm, the HR for OS is 0.77 (90% CI: 0.57-1.04; p=0.079); there is a 10% improvement in 8 yr OS (53% vs.43%; p=0.059); median OS is 8.9/6.6 yrs in chemo/control groups. In pts with tumors <4cm there is little OS difference (HR=0.89; p=0.31). While correlations with the new staging system yield inconclusive findings due to small sample size, it does show that larger tumors derive greater benefit from AC. For example, in 43 pts with tumors >7 cm (defined as T3 in the new AJCC system), the HR for OS was 0.53 (90% CI: 0.28-1.00; p=0.051). Conclusions: While not statistically significant, long term follow-up of this underpowered study shows a strong OS signal for all pts and for pts with tumors ≥4m. Our long-term data justifies AC in resected node negative NSCLC ≥4 cm in diameter.
Long-term outcomes and predictive factors in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) showing abiraterone withdrawal syndrome (AWS) after docetaxel (DOC) treatment.
Authors: Orazio Caffo, Francesca Maines, Chiara Trentin, Antonello Veccia, Enzo Galligioni
Journal: Journal of Clinical Oncology (2016)

324 Background: AWS has been rarely described as a possible PSA reduction, with or without radiological responses, observed after abiraterone acetate (AA) suspension due to disease progression. According to this possibility, all pts progressing under AA were usually monitored for at least 4 wks to evaluate if they developed AWS; if PSA decreased, the subsequent treatment was delayed until the occurrence of biochemical and/or radiological progression. The present study is aimed to assess long-term outcomes and predictive factors in DOC pre-treated mCRPC pts experiencing AWS. Methods: We evaluated a consecutive series of 73 pre-treated mCRPC pts, who received AA in our Hospital after DOC failure: all pts were treated with AA 1,000 mg po + prednisone 10 mg po daily; the treatment continued until progression disease (PD) which required to be confirmed by imaging. For each pt we have recorded the pre and post-AA clinical history, the treatment details and outcomes. All pts stopped AA due to progressive disease and AWS was defined by PSA reduction ≥ 25%, compared to the AA-end values, observed in the first month after AA stop. A logistic regression analysis was performed in order to assess the ability of a series of 18 selected clinical factors to predict AWS. Results: AWS was observed in 7 pts (9.5%) with a median duration of 17 wks (range 9-33). Two pts undergoing the 3-monthly radiographic restaging showed an objective response. A significant difference in terms of post-AA median OS was observed between AWS- and AWS+ pts (3.6 vs 27.9 mos; p = 0.02); this differences was confirmed by 1-month landmark analysis (4.6 vs 27.9 mos; p = 0.03). Among the factors, only the absence of pain at AA therapy baseline was able to predict the AWS: 100% of AWS+ pts were asymptomatic, compared to 64.6% of AWS- pts (p = 0.04). Conclusions: Despite AWS remains an unpredictable and rare phenomenon, it could represent a chance to delay the start of subsequent therapeutic line after AA failure. Moreover, our results seem to suggest that the occurrence of AWS may have a positive impact on the OS of mCRPC pts.
Noncancer endpoints in <i>BRCA1/2</i> carriers after risk-reducing salpingo-oophorectomy.
Authors: J. Cohen, L. Chiel, J. Stopfer, J. Powers, S. M. Domchek
Journal: Journal of Clinical Oncology (2010)

1513 Background: Risk reducing salpingo-oophorectomy (RRSO) significantly reduces the risk of breast and ovarian cancer in BRCA1 and BRCA2 mutation carriers (B1/2). As a result, RRSO is recommended for B1/2 once childbearing is complete, optimally, prior to age 40. Little is known about non-cancer endpoints in this population. Methods: Medical records were examined in 230 B1/2 who had previously undergone RRSO with a focus on bone health as well as the frequency of hypertension, hyperlipidemia, coronary artery disease (CAD), myocardial infarction (MI), diabetes, hypothyroidism and depression. DEXA scans were available and reviewed in 144 patients (63%). Results: The median age of women was 54; the median age at RRSO was 48. Of those DEXA scans available for review, 72% (104/144) were abnormal, (59% osteopenia and 13% osteoporosis). Among women who underwent RRSO prior to age 50, 72% (61/85) had osteopenia/osteoporosis. Of these 85 women, 71% (60/85) had a history of breast cancer (BC), 75% (45) of whom had osteopenia/osteoporosis. 60% (15/25) of women without BC were noted to have osteopenia. There were no reported cases of osteoporosis in those women with RRSO prior to age 50 and without BC. There were no differences in the median age of oophorectomy or time since oophorectomy in those with normal vs. abnormal DEXA scans. In other non-cancer endpoints, 18% of B1/2 (42/230) had hypertension, 20% (46/230) hyperlipidemia, 2% (5/230) CAD or MI, 2% (4/230) diabetes, 13% (29/230) hypothyroidism and 14% (32/230) depression. Conclusions: Here we report the prevalence of non-cancer endpoints in a cohort of B1/2 mutation carriers, and note a particularly high rate of osteopenia and osteoporosis in B1/2 with breast cancer undergoing RRSO prior to 50. Despite the risk reduction RRSO offers, attention should be paid to non-cancer endpoints, particularly bone health. Further work is ongoing to prospectively collect non-cancer endpoints, and to compare to an age matched group who has not undergone RRSO. No significant financial relationships to disclose.
Randomized phase II trial comparing the efficacy and safety of nintedanib versus sorafenib in patients with advanced hepatocellular carcinoma (HCC).
Authors: Daniel H. Palmer, Yuk Ting Ma, Markus Peck-Radosavljevic, Paul J. Ross, Janet Shirley Graham, Laetitia Fartoux, Andrzej Deptala, Arne Wenz, Julia Hocke, Arsene-Bienvenu Loembe, Tim Meyer
Journal: Journal of Clinical Oncology (2015)

238 Background: Nintedanib (N) is an oral, triple angiokinase inhibitor of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF) receptors. This randomized, multicenter, open-label, phase II study (NCT01004003; 1199.37) evaluated the efficacy and safety of N versus sorafenib (S) in patients with advanced HCC. Methods: Enrolled patients had unresectable advanced HCC, ECOG-PS ≤2, Child–Pugh score 5–6, alanine/aspartate aminotransferase (ALT/AST) ≤2× upper limit of normal, and ≥1 untreated measurable lesion or a previously treated lesion with progression (by RECIST 1.0). Patients were randomized 2:1 to N 200 mg bid or S 400 mg bid continuously in 28-day cycles, until intolerable adverse events (AEs) or disease progression (PD); treatment beyond PD was allowed if clinical benefit was perceived. Primary endpoint was time to progression (TTP) by independent central review (ICR; RECIST 1.0), and secondary endpoints were overall survival (OS) and investigator-assessed (IA) TTP. Results: Ninety-three patients were randomized to receive N (n=62) or S (n=31). At the cutoff date (15 July 2014), 77% of patients had a TTP event, and 70% had an OS event; 3 patients remained on treatment with 1 patient beyond PD. IA TTP was comparable between N and S (median 5.5 vs 3.8 months; HR 1.05 [95% CI: 0.63–1.76]), as was OS (median 11.9 vs 11.4 months; HR 0.88 [95% CI: 0.52–1.47]). ICR TTP data are pending. All patients reported an AE (CTCAE 3.0); more patients treated with S had Grade ≥3 AEs (68% vs 90%). AEs leading to dose reduction were higher with S (19% vs 42%), whereas AEs leading to drug discontinuation were higher with N (45% vs 23%). The only tyrosine kinase inhibitor class-specific AE reported in &gt;15% of patients was hand-foot skin reaction in the S arm. AEs previously observed with N and higher in this arm were diarrhea, vomiting, nausea, and AST increase, while blood bilirubin increase was higher with S. Rash was reported in &gt;15% of patients only in the S arm. Conclusions: N shows similar efficacy to S with respect to TTP and OS, with a manageable safety profile. Further studies of N in patients with advanced HCC are warranted. Clinical trial information: NCT01004003.
Intermittent chemotherapy in advanced unresectable colorectal cancer. An option for our patients?
Authors: E. Nadal, M. Majem, M. Navarro, L. Pareja, A. Pisa, V. Arrazubi, D. Pares, M. Martinez Villacampa, G. Soler, J. R. Germa
Journal: Journal of Clinical Oncology (2005)

3703 Background: Chemotherapy (CT) improves overall survival and quality of life in advanced unresectable colorectal cancer (auCRC) and CT has better outcome when administered early. Several schedules are active in auCRC, but optimal duration remains uncertain and general practice results in administering CT until progression, toxicity or patient’s decision. The purpose of this study is to identify which auCRC patients (pts) could benefit from stopping first line CT although no progressive disease has been observed without detriment in overall survival. Methods: all pts with CRC are prospectively recorded in our single institution-data base and are included in the same assistance protocol. 358 pts (224 M; 134 F) with auCRC have been analysed. Median age 61y (23,83);67% presented as auCRC at diagnosis and 33% appeared in the follow up; 46 pts had locoregional (LR) disease, 220 pts had distant metastasis (M) and 92 pts had LR + M. Number of metastatic sites: one, 64.7%; two, 26.3% and >two, 9%. All pts received CT. CT lines: Group 1, one line with 5FU: 150 pts (42%); group 2, one line with either CPT-11 or Oxaliplatin: 67 pts (19%); group 3, two or more lines: 141 pts (39%). CT was stopped between two lines for at least 3 months (m) in 80/148 pts (141 pts of group 3 + 7 pts of groups 1 and 2) with a median interval of 9 m (3–56). CT was stopped due to maintained response in 57/80 pts (71.3%), and 12 pts (15%) restarted the same CT scheme.Kaplan-Meier survival curves were compared with log rank test. We used X2 tests to determine association between continuous or intermittent CT with certain prognostic variables. Results: With a median follow-up of 24.7 m (3.5; 72.4), the median survival (MS) of all pts was 16.7m (14.7;18.6); MS of group 1: 12.5 m; MS of group 2: 14.5m; MS of group 3: 27.9m (p<0.0001). MS of initial auCRC: 13.3m; MS for progressive auCRC: 21.53m (p<0.01). MS of pts with continuous CT: 16.5 m; MS of pts that stopped CT for at least 3 months: 36.9m (p50y in the group of intermittent CT (p<0.05). Conclusions: there is a group of pts with auCRC that could benefit from interrupting CT and restarted CT when they progress even with the same schedule. Randomised trials are warranted in order to establish the optimal duration of CT in auCRC. No significant financial relationships to disclose.
Treatment of MCF-7 breast cancer cells with mono- and bispecific antisense oligonucleotides
Authors: M. Rubenstein, P. Tsui, P. Guinan
Journal: Journal of Clinical Oncology (2008)

14660 Background: Antisense against TGF-α (MR1) and EGFR (MR2), is efficacious against UACC 897 breast, PC-3 and LNCaP prostate, and T98G glioblastoma tumors in vitro and in vivo, and oligos against bcl-2 (MR4) are also efficacious against PC-3 and LNCaP in vitro. Methods: To enhance activity, “bispecifics” were constructed containing complementary DNA sequences (from MR1 or MR2) designed to bind mRNA about the initiation codons, and/or a similar sequence adjacent to the AUG site of mRNA encoding bcl-2. Tandem pairs were constructed: One had sequences for TGF-α and EGFR mRNA, but differed in 5’ to 3’ orientation (TGF-α/EGFR [MR12] and EGFR/TGF-α [MR21]); a second had binding sites associated with EGFR and bcl-2, also differing in orientation (EGFR/bcl-2 [MR24] and bcl-2/EGFR [MR42]). In studies targeting PC-3 and LNCaP cells, bispecifics demonstrated significant in vitro activity, and the second pair was significantly better than the original monospecifics. We extend these studies to the MCF-7 breast cancer model to determine whether bispecific oligos have similar anti-breast cancer activity. Results: Compared to lipofectin containing controls, MR2, MR12, MR21, MR4 MR24, MR42 produced significant (p < 0.001 for each oligo) inhibitions of 38.1, 13.4, 31.0, 46.8, 28.4 and 29.4%, respectively. Monospecific MR4 was significantly better than all other oligos tested: MR4 vs monospecific MR2 (p = 0.025); and MR4 vs bispecifics MR12 (p < 0.001), MR21 (p < 0.001), MR24 (p < 0.001) and MR42 (p < 0.001). Monospecific MR2 was also significantly better than bispecifics MR12 (p < 0.001), MR24 (p = 0.038) and MR42 (p = 0.037). In a 2’nd experiment cells were similarly incubated. Compared to lipofectin containing controls, MR2, MR12, MR21, MR4 MR24, MR42 produced significant inhibitions of 33.4 (p < 0.001), 13.2 (p = 0.005), 24.4 (p < 0.001), 31.1 (p < 0.001), 23.0 (p < 0.001) and 18.8% (p = 0.0002), respectively. In this experiment, MR2 and MR4 were similarly active (NS). Monospecific MR2 was significantly better than bispecifics MR12 (p = 0.004) and MR42 (p = 0.031). Monospecific MR4 was also significantly better than bispecifics MR12 (p = 0.0005) and MR42 (p = 0.009). Conclusions: Against MCF-7 cells monospecific MR2 and MR4 are better than bispecific MR12, MR21, MR24 and MR42 oligos for inhibition of cell growth. No significant financial relationships to disclose.
Development and validation of a new prognostic score of death in patients with hepatocellular carcinoma
Authors: C. Tournoux, X. Paoletti, F. Bonnetain, M. Doffoel, O. Bouché, L. Bedenne, J. Barbare
Journal: Journal of Clinical Oncology (2008)

4601 Background: Four classic staging systems are mainly used to predict overall survival (OS) in patients with hepatocellular carcinoma (HCC). Collette et al. (JCO, 2007 ASCO Annual Meeting Proc. Vol 25, No. 18S, 2007: 4589) recently demonstrated that CLIP had the best predictive value in patients with advanced HCC. It could be improved with a performance status (PS) criterion as in the BCLC score. In this communication, we develop a new OS prognostic score for advanced HCC that we validate on an independent dataset. Methods: Prognostic score was derived from a negative randomized trial conducted by the Fédération Francophone de Cancérologie Digestive (FFCD) comparing Tamoxifen to supportive care. External validation was assessed on the CHOC trial (FFCD), comparing LAR- octreotide to placebo. Model development included demographic and tumour characteristics (aetiology, Child-Pugh stage, number and size of the tumour, vascular extension and metastasis), clinical variables (WHO PS, oedema, jaundice, encephalopathy and ascite), and biological variables. Endpoint was OS. Variables reaching significance at p-value <0.1 were included in a multivariate Cox model. Shemper explained variation measure and Harrell’s C discrimination index of the competing scores were studied. Results: A total of 416 and 271 patients (median survival of 4.4 and 6.8 months) were included in the development and validation analysis respectively. The final model contained tumor morphology, portal obstruction, metastasis, PS, ascite, jaundice, serum alpha-fetoprotein and alkaline phosphatases. This new score explained 13.5% of the survival variability as compared to 11.5% for the CLIP alone and to 13.3% for the CLIP + WHO PS. Discrimination ranged from 0.64 (CLIP) to 0.66 (new score) and 0.67 (CLIP+WHO PS). These results as well as Collette et al ranking were validated on the independent dataset. Conclusions: he new score and the CLIP + WHO PS outperformed other staging scores for predictive accuracy and discrimination. However overall performances remain disappointing. No significant financial relationships to disclose.
Pelvic radiotherapy and chemotherapy with or without surgery in the management of metastatic rectal cancer
Authors: A. Zouhair, M. Ozsahin, M. Ychou, M. Montemurro, J. B. Dubois, R. O. Mirimanoff, D. Azria
Journal: Journal of Clinical Oncology (2008)

15030 Background: To assess the role of pelvic radiotherapy (RT) in the outcome of patients treated with chemotherapy (CT) with or without surgery in the management of metastatic rectal cancer. Methods: Between July 1996 and December 2002, 78 patients with rectal cancer metastatic at initial diagnosis were enrolled in this study. Patients had biopsy proven rectal adenocarcinoma, and complete initial diagnostic work-up confirmed metastatic disease (M1) in all patients. There were 3 patients with cT2 tumors, 73 with cT3, and 2 with cT4. According to the N-classification, there were 32 patients with cN0, 45 with cN1, and 1 patient with cN0 disease. Symptoms were rectal bleeding and/or pain in the majority of the patients. All patients received CT and/or RT with (n = 47 patients; 60%) or without (n = 31 patients; 40%) curative surgery (anterior resection in 81% of patients, and abdominoperineal amputation in 19%). CT consisted of 5-fluorouracil and leucovorin in the majority of patients. Pelvic RT was delivered using 6–18 MV high-energy photons following computer-tomography-based conformal planning. Median RT dose was 46 Gy at 2 Gy per fraction. Symptoms secondary to primary tumors were reassessed after pelvic RT. Results: Following pelvic RT, good clinical response was obtained with complete resolution of initial symptoms in 57 patients (73%), and partial resolution in 21 (27%). Median time to pelvic progression was 12 months (n = 7). Two-year overall survival and pelvic control rates were 43% (95% confidence interval [CI]: 31–56%) and 88% (95% CI: 77–98%), respectively. There was no difference in terms of pelvic progression between the patients treated with or without surgery (3[13%] of 47 vs. 4[6%] of 31, respectively; p = 0.43). The majority (n = 72) of the patients, as expected, died from their metastatic disease. No relevant late RT toxicity according to Common Terminology Criteria for Adverse Events, version 3.0 was observed. Conclusions: Pelvic RT combined with chemotherapy is efficient in symptomatic patients with rectal cancer, and should be considered in the management of metastatic rectal cancer in the light of increasingly efficient CT and/or emerging targeted therapies. No significant financial relationships to disclose.