tbuckley/cabot-search huggingface dataset:
Effect of combination radioimmunotherapy (RAIT) and chemoimmunotherapy on therapeutic response and toxicity in xenograft models of human pancreatic carcinoma: First experimental studies.
Authors: R. M. Sharkey, H. Karacay, S. V. Govindan, S. Moon, A. Mostafa, D. M. Goldenberg
Journal: Journal of Clinical Oncology (2011)

206 Background: Preclinical and early clinical data with RAIT involving a 90 Y-labeled antibody to a pancreatic mucin antigen (hPAM4, clivatuzumab tetraxetan) have shown promising therapeutic activity in combination with gemcitabine. Selective targeting of therapeutic drugs using antibody-drug conjugates (ADC) might be useful in pancreatic cancer therapy. Methods: ADCs composed of SN-38 coupled to an internalizing anti-TROP-2 antibody, an antigen found on many epithelial cancers, or to the non-internalizing anti-mucin humanized IgG, were prepared (6 SN-38/IgG). Nude mice bearing s.c. Capan-1 or BxPC3 xenografts (∼0.35 cm 3 ) were given multiple ADC doses (twice weekly, 4 weeks) or appropriate controls of a non-targeting IgG-SN-38 conjugate or irinotecan. Other groups of animals were treated with the ADC conjugates and RAIT, using RAIT at 60% and 100% of its MTD. The endpoint was time to progress to 3.0 cm 3 (TTP), with animals monitored up to 22 weeks. Results: ADCs alone were each able to inhibit tumor growth significantly compared to untreated animals. The specificity of the effect was a dose-dependent and related to antigen saturation at higher doses. When ADC was combined with RAIT, TTP improved significantly and more animals were tumor-free. An effective ADC dose could be combined even with RAIT given at its MTD, achieving enhanced efficacy with minimal additional toxicity. ADC + RAIT treatments were best when RAIT was given 1-2 weeks before, the same day, or within 1 week after the ADC treatment, but delaying RAIT for 2 weeks after ADC treatment reduced efficacy. The same anti-pancreatic mucin antibody, hPAM4, could be used in the combination treatment both as RAIT and as an ADC without losing effectiveness. Conclusions: These studies show the feasibility of using ADC for the treatment of pancreatic cancer, and for combining antibody drug- and radionuclide-targeted therapeutics for improved efficacy with minimal toxicity. Supported in part from NCI grant R01 CA115755. [Table: see text]
Continuing or ceasing bevacizumab at disease progression: Results from the CABARET study, a prospective randomized phase II trial in patients with recurrent glioblastoma.
Authors: Elizabeth J. Hovey, Kathryn Maree Field, Mark Rosenthal, Anna K. Nowak, Lawrence Cher, Helen Wheeler, Elizabeth Barnes, Pramit Phal, Ann Livingstone, Kate Sawkins, John Simes
Journal: Journal of Clinical Oncology (2015)

2003 Background: In patients (pts) with recurrent glioblastoma (rGBM), the benefit of bevacizumab beyond progression (BBP) remains uncertain. Retrospective studies of pts with rGBM receiving BBP have been inconclusive. This study prospectively evaluated BBP in patients with rGBM who experienced initial progression while on bevacizumab (Bev). Methods: CABARET is a prospective randomized Phase 2 study of pts at first recurrence of GBM (rGBM) who had previously been treated with surgery, radiotherapy and temozolomide. Pts were randomized to carboplatin plus Bev or Bev monotherapy (Part 1). On progression, eligible pts were stratified according to planned additional chemotherapy and then randomized again to continue or cease Bev (Part 2). Those pts on the Bev monotherapy arm in Part 1 could receive carboplatin or supportive care and those who had received Bev + carboplatin in Part 1, ceased carboplatin and could receive temozolomide, etoposide or supportive care; according to clinician choice. Part 2 endpoints included response rate (RR), progression-free survival (PFS) and overall survival (OS). Results: Of 120 pts who received treatment in Part 1, 48 (40%) continued to Part 2, with 23 pts continuing Bev and 25 pts ceasing Bev. The median time on treatment was 1.2 months. There were no radiological responses in either arm. Median PFS (Bev vs no Bev) was 1.8 versus 2.0 months (HR 1.08, 95% CI 0.59–1.96, p = 0.81). Median OS was 3.4 versus 3.0 months (HR 0.84, 95% CI 0.47–1.50, p = 0.56). There were no treatment-related deaths or unexpected serious drug-related adverse events. Preliminary assessment of quality of life scores shows no difference between arms. Conclusions: Continuing Bev after progression of rGBM did not improve PFS or OS in this prospective study. Clinical trial information: ACTRN12610000915055.
Accuracy of CT-guided transthoracic needle biopsy of lung lesions: Results of 612 consecutive procedures
Authors: U. Ricardi, A. M. Priola, S. M. Priola, S. Novello, A. Cataldi, B. Crida, G. V. Scagliotti, C. Fava
Journal: Journal of Clinical Oncology (2007)

18022 Background: CT-guided transthoracic needle biopsy (TNB) is commonly used in diagnostic work-up of lung lesions. The availability of a on-site pathologist at the time of the procedure ameliorate its sensitivity, reduce the number of biopsies and false negatives. Methods: 612 procedures (608 patients with a CT-documented central or peripheral pulmonary lesion) performed at S. Luigi Hospital between November 2002 and August 2005 were prospectively analyzed; 66% males, median age was 66 years (range 29–87). Ineligibility criteria for the procedure included severe coagulopathy, previous contralateral pneumonectomy, lesions with a maximum diameter less than 5 mm or the impossibility to understand the procedure or to maintain the clinostatism for the time of the procedure. The on-site pathologist assigned to each specimen a semiquantitative score: 0 for bloody sample without other cells, 1 for aspecific benign or inflammatory cells, 2 for malignant cells without histotype characterization and 3 for well established benign or malignant histotype. Results: Most of the procedures was performed by fine needle aspiration biopsy, while in a minority of cases a tru-cut biopsy was requested. In 57.2% of the cases a single transthoracic access (range 1–4) was used and in 31% the procedure was repeated on the basis of the radiologist/pathologist judgment. In 154 patients a surgical resection was subsequently performed, while 454 were patients non-surgical. A score of 3 was obtained in 71% of cases (88% malignancies), 2 in 12.5%, 1 in 7.5% and 0 in 9%. A definitive diagnosis was made in 83.5% of procedures, while a score of 0–1 was assigned in 101 cases. Among 458 malignancies there were 411 lung cancer, 7 non-epithelial cancers and 40 metastases with only 1 false positive. The diagnostic accuracy for benign and malignant lesions was 67% and 92%, respectively (Pearson’s test p&lt;0.005) with overall diagnostic accuracy of 83.3%. The variables affecting diagnostic accuracy were final diagnosis (benign 67%, malignant 92%, p&lt;0.001) and lesion size (lesion 5 cm 78%, p&lt;0.05). The presence of cavitation or necrotic areas and location of the lesion didn’t affect the diagnostic accuracy. Conclusion: In consecutive cases of CT-guided TNB final diagnosis and lesion size affect diagnostic accuracy. No significant financial relationships to disclose.
Era-by-era improvement in survival for elderly patients with Hodgkin lymphoma; outcome data from a large population-based cohort
Authors: M.J. Bishton, R. Hubbard, R. Witherall, S.G. Jones, F. Richardson, E.J. James, V. Sovani, E.M. Bessell, A.P. Haynes, A.K. McMillan, C.P. Fox
Journal: Annals of Oncology (2015)
Adjuvant or neoadjuvant chemotherapy in early-stage non-small cell lung cancer (NSCLC): How would staging affect the patients (pts) treated?
Authors: J. P. Van Meerbeeck, M. Nicholson, D. Gilligan, H. J. Groen, M. Nankivell, C. Pugh, R. Stephens
Journal: Journal of Clinical Oncology (2008)

7509 Background: Both adjuvant chemotherapy (ACT) (HR 0.89, Pignon 2006 ) and neoadjuvant chemotherapy (NCT) (HR 0.88, Gilligan 2007) appear to result in comparable survival benefit in pts with early stage NSCLC. ASCO currently recommends ACT for pts with completely resected stages pII-III NSCLC (Pisters, 2007), as the pooled benefit is largest in these stages. A formal large scale comparative trial between both approaches seems appropriate, albeit requiring a large sample size. We assume that the outcome of such a trial is likely to be confounded by clinicopathological stage migration, as the decision to give NCT is based on clinical staging, which is known to be inaccurate (D'Cunha, 2005). Methods: Exploratory analyses of the 463 pts (239 surgery alone (S), 224 NCT + surgery (NCT-S)) included in a large randomised trial investigating the role of platinum-based NCT (LU22-NVALT 2-EORTC 08012), in whom detailed clinical and pathological staging data [UICC-6, Mountain, 1997] is available, in order 1. to estimate the directions and magnitude of clinicopathological stage migration in pts with resectable NSCLC. 2. to assess its impact on the selection of pts receiving NCT or ACT according to the ASCO-guideline. Results: Clinical staging is well balanced between both treatment arms. Stage migration per stage and treatment arm is shown in the Table. 36% of S-pts and 25% of CT-S pts migrate up and 15% and 20% down, respectively. Applying the ASCO guideline, 119 (50%) S pts who had pathological stage II/III would receive ACT. However, the use of clinical staging to select pts for NCT would result in only 35% pts receiving this treatment. Conclusions: Besides the need for a large sample size, any future comparison between ACT and NCT in early stage NSCLC based on the current ASCO-guideline, will have to compensate for a selection bias by stage migration in favour of ACT. Clinical staging needs hence to be as accurate as possible. Clinical Staging S-pts (n= 239) NCT-S pts (n= 224) I II III I II III Pathological staging 0 0 0 0 5 (2%) 2 (1%) 1 (<1%) I 82 (34%) 26 (11%) 5 (2%) 95 (42%) 31 (14%) 6 (3%) II 34 (14%) 31 (13%) 5 (2%) 31 (14%) 19 (8%) 1 (<1%) III 26 (11%) 19 (8%) 4 (2%) 13 (6%) 11 (5%) 7 (3%) IV 2 (1%) 5 (2%) 0 2 (1%) 0 0 Total 144 (60%) 81 (34%) 14 (6%) 146 (65%) 63 (28%) 15 (7%) Figures are numbers and (%) of each treatment arm No significant financial relationships to disclose.
Evaluation of mRNA markers for micrometastases detection by RT-PCR in lymph nodes (LN), peripheral blood (PB) and bone marrow (BM) of breast cancer patients (pts)
Authors: A. M. Morelle, A. Frasson, F. Zerwes, S. Alves, G. Devenz, C. M. Silveira, A. V. Nectoux, M. Wagner, B. Garicochea
Journal: Journal of Clinical Oncology (2006)

20068 Background: Previous RT-PCR study showed that hMAM and CEA mRNA could be detected in 95% and 78% breast carcinomas, respectively. Analyzed in normal LN, these two markers were the only ones not expressed, compared to other mRNA markers which could be detected in a variable number of cases (Marchetti 2001). We evaluate the expression of CEA and hMAM mRNA in breast cancer pts in order to investigate if the identification of these transcripts could be correlated to in the LN, PB and BM. Methods: Tumor, normal gland, LN and PB were obtained from 49 breast cancer pts who have been referred to surgery during the period of Jun/2000 to Jan/2004.BM could be obtained from 21 of these cases. Before the manipulation of the tumor, 5 mL of PB was collected and 5 mL of BM was aspirated from the iliac crest. First level axillary LN were sectioned in two. One of the halves was immediately frozen in liquid nitrogen. CEA and hMAM transcripts have been analysed by RT-PCR. Results: Tumors were positive for CEA in 38 (77.6%) cases and LN were positive in 15 cases (36.7%). 6/49 pts expressed CEA in normal breast (12.2%). Five of these, tumor also expressed CEA. Two pts (4.1%) showed CEA expression in PB and in BM. One patient expressed CEA in BM but not in PB. All pts that showed expression in PB, BM and LN, also showed transcript of CEA in tumor. hMAM transcripts were found in 39 (79.6%) normal gland tissue and in 41 of tumor samples (85.7%). LN were positive to hMAM in 12 cases (24.5%). 5 of these (10.2%) were also positive in PB and BM samples. The pts showing hMAM expression in PB, BM and LN also showed its expression in neoplasic tissue. Analyzing both markers, two pts showed the expression of CEA and hMAM in the PB and BM samples. In 21 of the 49 cases the comparison of hMAM and CEA was possible to be performed in all tissues. CEA and hMAM expression associated to larger number of LN affected. Conclusions: CEA and hMAM transcripts can be detected in majority of breast cancer tissue. Specificity of hMAM seems to be higher than CEA, which can be detected in more than 10% of non-tumor breast tissue. Synchronicity of CEA or hMAM expression in the tumor and in extra-mammary sites was high, suggesting that these markers may provide an interesting strategy for follow-up micrometastatic disease. No significant financial relationships to disclose.
A phase II trial of docetaxel and cisplatin combination in patients with locally advanced undifferentiated carcinoma of nasopharyngeal type (UCNT): Study update
Authors: M. Yamouni, K. A. Benhadji, Y. Beldjilali, I. Lahfa, D. Yekrou, L. Djellali, M. Brahimi, K. Bouzid
Journal: Journal of Clinical Oncology (2006)

5579 Background: The standard treatment of locally advanced undifferentiated carcinoma of nasopharyngeal type (UCNT) is cisplatin based chemotherapy followed by locoregional radiotherapy. The purpose of this study is to assess the antitumor activity and toxicity of a new neoadjuvant chemotherapy regimen combining docetaxel (D) and cisplatin (C). Patients and Methods: Previously untreated patients (pts) with histologically diagnosed locally advanced UCNT (Stages IVa and IVb TNM/UICC 1997) received D 75 mg/m 2 and C 75 mg/m 2 both on day 1, cycles were repeated every 21 days. Every pts received three cycles in a neoadjuvant setting before radiotherapy (4 to 6 weeks after the third cycle of DC). Pts were evaluated by clinical examination, CT scan of nasopharynx and nasofibroscopy with biopsy. Primary end point was tumor response. Secondary end points were disease free survival (DFS), toxicity and overall survival. Results: 75 pts were enrolled in this trial, 54 males and 21 females with a median age of 41 years (range 18–69), WHO performance status of 0–1 in 71 pts and 2 in 4 pts. 19 pts had stage IVa and 56 pts had stage IVb. Toxicity, tumor response and survival over tree years were assessable in 75 pts. After 225 cycles, grade 3 &amp; 4 toxicity (NCI-CTC 2.0) were: neutropenia (12%), febrile neutropenia (2%), anemia (1%), nausea and vomiting (23%), diarrhea (8%), mucositis (1%), reversible alopecia (70%). Two pts had onycolysis. Response rates for the 75 pts were: complete pathologic response 37% (28 pts), partial response 52% (39 pts), stable disease 8% (6 pts) and progression 3% (2 pts). The overall response rate was 89%. 74 pts (98%) had complete response after radiotherapy and one patient had stable disease. 31 patients had recurrence: 25 locoregional, and 6 metastatic (3 with bone metastasis, 2 hepatic metastasis and 1 cerebral metastasis). DFS and overall survival at 3 years were respectively 57% and 65%. Conclusion: DC chemotherapy followed by radiation therapy is an effective regimen for the treatment of advanced UCNT. This treatment has an acceptable safety profile. These data need to be compared to concurrent chemoradiotherapy to assess the best strategy for the management of advanced UCNT. [Table: see text]
Tasquinimod Mechanism of Action Biomarkers: Correlation with PFS and Survival in Men with Metastatic Castrate Resistant Prostate Cancer Treated in a Randomized Phase 2 Trial
Authors: M. Carducci, A. Armstrong, M. Häggman, W.M. Stadler, J.R. Gingrich, V. Assikis, G. Forsberg, A. Olsson, Ö. Nordle, R. Pili
Journal: Annals of Oncology (2012)
Sentinel Lymph Node Biopsy With Metastasis: Can Axillary Dissection Be Avoided in Some Patients With Breast Cancer?
Authors: Carol Reynolds, Rosemarie Mick, John H. Donohue, Clive S. Grant, David R. Farley, Linda S. Callans, Susan G. Orel, Gary L. Keeney, Thomas J. Lawton, Brian J. Czerniecki
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Recent studies have suggested that the sentinel lymph node (SLN) biopsy is an accurate alternative staging procedure for women with breast cancer. The goal of this study was to identify a subset of breast cancer patients in whom metastatic disease was confined only to the SLN. MATERIALS AND METHODS: From two institutions, we recruited 222 women with breast cancer for SLN biopsy. A SLN biopsy was performed in each patient, followed by an axillary dissection in 182 patients. Histologic and immunohistochemical cytokeratin stains were used on all SLNs. RESULTS: The SLN was identified in 220 (97.8%) of the 225 biopsies. Evidence of metastatic breast cancer in the SLN was found in 60 (27.0%) of the 222 patients. Of these patients, 32 (53.3%) had evidence of tumor in the SLN only. By multivariate analysis, two factors were found to be significantly associated with a higher likelihood of tumor involvement in the non-SLNs: primary tumor size larger than 2.0 cm (P = .0004) and macrometastasis (&gt; 2.0 mm) in the SLN (P = .002). Additional analysis revealed that none (0%; 95% confidence interval, 0% to 18.5%) of the 18 patients with primary tumors ≤ 2.0 cm and micrometastasis to the SLN had remaining axillary lymph node involvement. CONCLUSION: The primary tumor size and metastasis size in the SLN are independent factors in predicting the incidence of tumor in the non-SLNs. Therefore, the SLN biopsy alone may be adequate for staging and/or therapy decision making in patients with primary breast tumors ≤ 2.0 cm and micrometastasis in the SLN.
AVAGAST: A randomized, double-blind, placebo-controlled, phase III study of first-line capecitabine and cisplatin plus bevacizumab or placebo in patients with advanced gastric cancer (AGC).
Authors: Y. Kang, A. Ohtsu, E. Van Cutsem, S. Y. Rha, A. Sawaki, S. Park, H. Lim, J. Wu, B. Langer, M. A. Shah
Journal: Journal of Clinical Oncology (2010)

LBA4007 Background: The median survival for patients (pts) with AGC in most phase III studies is less than 1 year. The addition of bevacizumab (bev) to chemotherapy (chemo) is supported by a strong preclinical rationale and by phase II evaluation. AVAGAST is the first randomized study to compare the efficacy and safety of bev + chemo vs placebo + chemo. Methods: Pts with inoperable, locally advanced or metastatic stomach/gastroesophageal junction adenocarcinoma with no prior therapy were randomized 1:1 to capecitabine (cape, or 5-FU) + cisplatin (cis) and either bev (7.5 mg/kg iv) or placebo q3w. Stratification variables: geographical region, fluoropyrimidine treatment, disease status. Cis was given for 6 cycles; bev/placebo + cape/5-FU were given until disease progression or unmanageable toxicity. Primary objective: compare overall survival (OS); secondary objectives: compare progression-free survival (PFS), overall response rate (ORR), and safety (as overseen by an independent DSMB). Results: From Sep 2007 to Dec 2008, 774 pts were enrolled. Treatment arms were balanced. Approx 95% of pts were metastatic. Two-thirds of pts were male, 49% of pts were from Asia/Pacific, 32% from Europe and 19% from the Americas. Median OS was 10.1 months with chemo + placebo and 12.1 months with chemo + bev in the intent-to-treat population (HR 0.87; p=0.1002). Median OS according to geographical region was 6.8 vs. 11.5 months (HR 0.63) in the Americas, 8.6 vs. 11.1 months (HR 0.85) in Europe and 12.1 vs. 13.9 months in Asia-Pacific (HR 0.97). Secondary endpoints and AEs of special interest for Bev are summarized below ( Table ). Conclusions: While the primary endpoint was not met (median OS HR 0.87; p=0.1002), there was a significant improvement in PFS and ORR and an acceptable safety profile for bev + chemo in patients with AGC. [Table: see text] [Table: see text]
Obesity and menopausal status as determinants of procarcinogenic breast inflammation.
Authors: Neil M. Iyengar, Patrick Glyn Morris, Xi Kathy Zhou, Ayca Gucalp, Dilip D. Giri, Michael Harbus, Domenick J Falcone, Linda T. Vahdat, Mahmoud I. Awad, Margaret D Krasne, Kotha Subbaramaiah, Monica Morrow, Clifford A. Hudis, Andrew Dannenberg
Journal: Journal of Clinical Oncology (2014)

40 Background: Chronic inflammation predisposes to several malignancies. We previously demonstrated an obesity → inflammation → aromatase axis in breast tissue. As obesity is a risk factor for postmenopausal (PoM) but not premenopausal (PreM) breast cancer (BC), we examined whether menopause and body mass index (BMI) independently impact breast white adipose tissue (WAT) inflammation. Methods: WAT was prospectively collected from patients (pts) from 04/10 to 08/13. WAT inflammation, detected by CD68 immunohistochemistry, was defined by the presence of dead or dying adipocytes surrounded by an envelope of macrophages known as crown-like structures of the breast (CLS-B). WAT area was measured with NIH Image J. Adipocyte diameter was measured with Canvas 11 Software. Endpoints were 1) CLS-B (+/-) and 2) CLS-B/cm 2 . Clinicopathologic associations with CLS-B were analyzed by logistic regression and Fisher’s exact test. Results: WAT (237 mastectomies, 13 abdominal reconstructions) was obtained from 238 pts; median age 48 (range 22 to 90). CLS-B occurrence and number of CLS-B/cm 2 were greater in overweight/obese (BMI ≥ 25) and PoM pts compared to lean (BMI &lt; 25) and PreM pts (Table). In multivariable analyses, BMI and PoM state were independently associated with CLS-B presence (p &lt;.01 and p = .04) and greater CLS-B/cm 2 (p &lt; .01 and p = .01). PoM pts had larger mean adipocyte diameter (105.2 +/- 14.0 μ) than PreM pts (95.7 +/-15.6 μ; p &lt; 0.01). In pts with bilateral breast WAT and abdominal WAT, concordant CLS status (+/-) was found in 49/63 (78%) and 10/13 (77%) pts, respectively. Conclusions: Breast WAT inflammation (both presence and severity), which we have previously linked to increased aromatase activity, is associated with both increased BMI and menopause. These findings can explain the increased risk of estrogen receptor–positive BC with obesity and PoM status and may also provide targets for rational therapies. [Table: see text]