tbuckley/cabot-search huggingface dataset:
<sup>90</sup>Y radioembolization for neuroendocrine cancers liver metastases provides sustained therapeutic effect with minimal toxicity.
Authors: Andrew S. Kennedy, Maha Elkordy, Elizabeth Estill Campbell, Brent Albertson, Scott Lee Sailer, Margaret Ann Deutsch
Journal: Journal of Clinical Oncology (2012)

343 Background: Radioembolization (RE) is the delivery of radioactive microspheres ( 90 Y) via the hepatic artery, which permanently implant preferentially in metastatic lesions, sparing adjacent normal liver. Metastatic neuroendocrine tumors in the liver are a common clinical problem which can be treated with RE. It is an outpatient procedure performed with increasing frequency worldwide for a variety of solid tumor types. Methods: A single institution retrospective review of all neuroendocrine patients treated with radioactive resin microspheres to control hepatic metastases. Details reviewed included: specifics of treatment and delivery, RECIST response at 3 and 6 months, acute and delayed radiation toxicities by CTC3ae, and analyses of tumor and radiation factors related to response and liver control. Results: A total of 56 patients; 26 male, 30 female, received a total of 85 separate treatments with resin 90 Y microspheres. Treatment volume was all hepatic tumors with each treatment, usually selective whole liver in one fraction. Whole liver in 1 treatment comprised 86%, right lobe only in 10% and left lobe in 4%. Thirty-six patients (64.3%) received 1 treatment, 12 patients 2 fractions, 7 patients 3 fractions, and 1 patient 4 fractions. The median activity of 90 Y delivered was 1.49 GBq (0.35 – 2.9 GBq). BSA approach was used for pretreatment activity calculations for all patients, with median of 100% planned activity delivered (26% - 147%). No grade 4 toxicities occurred, and only two grade 3 events were found (gastric ulcers). The median follow up is 24.2 mo. (1 – 93.4 mo.). RECIST at 3 and 6 months: CR 6.5%, SD 49.1%, PR 42.6% and PD 1.6%. Delivered activity (GBq) was associated with PR at 3 months (p=0.07, two-tailed t-test). Conclusions: Our experience is consistent with other published reports confirming the efficacy and low toxicity of this liver-directed ablative approach for unresectable neuroendocrine carcinomas. Multiple treatments to the whole liver were well tolerated. The BSA method of pretreatment radioactivity estimation is useful and safe in this tumor type.
Lobular neoplasia on core biopsy: Is excision always indicated?
Authors: C. A. Makarewich, K. M. Rosenkranz
Journal: Journal of Clinical Oncology (2011)

75 Background: Lobular neoplasia (LN) is a continuum of rare, noninvasive lesions of the breast including lobular carcinoma in situ and atypical lobular hyperplasia. Current management is controversial and often includes excisional biopsy in women diagnosed with LN on percutaneous core biopsy (PCB) to exclude an occult malignancy. This strategy is based on retrospective data in women undergoing selective excisions. We performed routine excision of all lesions diagnosed as LN in our institution in order to ascertain a more accurate assessment of pathologic upgrade. Methods: Retrospective review of all prospectively collected cases of LN treated in a single institution from 2007-2010. Excisional biopsies were performed in all cases of LN excepting one (patient declined). Histologic findings of excisional biopsies were reviewed to assess the rate of pathologic upgrade. Results: Of the 2,289 PCBs performed during the study period, LN was found in 23 cases (1.0%). Twenty two (0.96%) cases proceeded to excisional biopsy. On final pathology, malignancy was found in 4 patients (18%). Two of 22 (9%) women were upgraded to ductal carcinoma in situ (DCIS) (both intermediate grade with foci of &lt;1mm and 4mm) and 2/22 (9%) women were diagnosed with invasive lobular carcinoma. Conclusions: While 18% of women in our series had upgraded pathology at the time of excisional biopsy, we support selective rather than routine excisional biopsy. One of the invasive diagnoses was an incidental finding unrelated to the microcalcifications for which biopsy was initially performed. In the second case of invasive disease, the upgraded lesion was a mass identified on MRI performed for surgical planning in a woman already diagnosed with breast cancer. In both cases of DCIS, the area of malignancy was small (&lt;1mm and 4mm) and of uncertain clinical significance. Based on these findings, we do not recommend routine excision of all LN identified on PCB. Cases in which the lesion is associated with a radiographic mass and/or is identified in a breast with a synchronous malignancy do warrant excisional biopsy. Patients without these high risk features can be counseled on the risks of malignancy and given the option of observation with close follow up.
Oncogenic <i>MET</i> as an Effective Therapeutic Target in Non–Small Cell Lung Cancer Resistant to EGFR Inhibitors: The Rise of the Phoenix
Authors: Livio Trusolino
Journal: Cancer Discovery (2016)

Anecdotal reports have shown that concomitant inhibition of EGFR and MET can be clinically effective in patients with non-small cell lung cancer carrying EGFR mutations and MET amplification, but large phase III trials in genetically unselected individuals have failed to confirm the benefit of this combination therapy. A new study corroborates the evidence that lung cancer susceptibility to EGFR and MET blockade is sustained by genetically based activation of both targets and identifies a mutation in MET that confers acquired resistance to standard MET inhibitors hitting the active kinase, yet is vulnerable to other MET-directed compounds with a different binding mode. Cancer Discov; 6(12); 1306-8. ©2016 AACR.See related article by Bahcall and colleagues, p. 1334.
Trascriptome Analysis of Bone Marrow CD14+ Monocytes Revealed Differential Expression Profiles in Symptomatic Multiple Myeloma (MM) Compared to Smoldering MM and Monoclonal Gammopathy of Undetermined Significance
Authors: Marco Peronaci, Paola Storti, Domenica Ronchetti, Luca Agnelli, Marina Bolzoni, Daniela Guasco, Denise Toscani, Benedetta Dalla Palma, Sabrina Bonomini, Gabriella Sammarelli, Luisa Craviotto, Antonino Neri, Franco Aversa, Nicola Giuliani
Journal: Blood (2012)
High-Throughput Immunoglobulin Gene Sequencing Quantifies Minimal Residual Disease in CLL with 10e-6 Sensitivity and Strongly Predicts Relapse After Allogeneic Hematopoietic Cell Transplantation
Authors: Aaron C. Logan, Malek Faham, Victoria Carlton, Jianbiao Zheng, Martin Moorhead, Tom Willis, Carol D. Jones, Melody B. Zhang, Amna N. Waqar, James L. Zehnder, David B. Miklos
Journal: Blood (2011)
Urinary Met level as a novel biomarker for urothelial carcinoma of the bladder.
Authors: M. Sorbellini, B. McNeil, B. Cohen, G. Athauda, A. Giubellino, J. Coleman, G. J. Netto, R. H. Getzenberg, W. Linehan, D. P. Bottaro
Journal: Journal of Clinical Oncology (2011)

257 Background: To determine whether urinary soluble Met (sMet) can differentiate between benign conditions and bladder cancer (CaB), and in cases of bladder cancer, between different stages of transitional cell carcinoma (TCC). Methods: Urinary samples from patients with (Total: 63, pTa: 12, pTis: 22, pT1: 13, ≥ pT2: 16) and without (Total: 27) CaB from three different institutions were prospectively collected prior to cystosopy, TURBT or cystectomy. sMet levels were determined by electrochemiluminescence immunoassay and normalized to urinary creatinine values. Normalized sMet values were compared to final pathologic stage. AUC values were obtained comparing patients with and without TCC. Results: Urinary sMet levels accurately differentiated between patients with and without CaB (AUC: 78%, sensitivity, specificity and negative predictive value were: 68%, 78% and 95%, respectively), patients with no CaB and those with lamina propria invasion (AUC: 79%, sensitivity, specificity and negative predictive value were: 65%, 81% and 95%, respectively) and patients with no CaB and those with muscle invasive CaB (AUC: 85%, sensitivity, specificity and negative predictive value were: 75%, 83% and 97%, respectively). Conclusions: Urinary sMet levels accurately distinguish patients with CaB from those without, and between patients with different CaB stages. These results suggest that urinary sMet may have utility as a bladder cancer marker for screening, treatment follow-up and clinical trial design. No significant financial relationships to disclose.
Navigation of sentinel node biopsy and selective axillary dissection using 3D-CT mammary lymphography with the arm lymph flow enhancement.
Authors: K. Yamashita, K. Shimizu, S. Haga
Journal: Journal of Clinical Oncology (2011)

98 Background: In early breast cancer, the presence of metastasis in axillary lymph nodes (AN) is an important factor in prognosis and further treatment. However, AN dissection causes many complications such as contracture of shoulder joint, lymph edema, and paralysis of upper extremities. Sentinel node (SN) biopsy provides us a valuable information about no need to dissect AN for node-negative patients. However, on node-positive patients, the conventional AN dissection has been performed. 3D-CT lymphography (LG) can show the precise individual lymphatic flow not only from the breast tumor to SN but also from SN to venous angle, which means breast lymphatic channel. We applied 3D-CT LG to distinguish them from the arm channel to avoid any arm complications. Methods: 3D-CT LG was performed before surgery to mark SN on the skin. Above the tumor and near the areola and the arm pit, 2 ml of iopamidol 300 was injected subcutaneously. Images of CT scan were taken at 1, 3, and 10 min after injection. They were reconstructed to produce a 3D image of lymph ducts and lymph nodes by the volume rendering software. The axillary node groups were classified to 5 groups as described before. The arm lymph channel was classified to 4 regions. SN biopsy and AN sampling were performed by dye-staining method using endoscopy. Results: We have performed 3D-CT LG on 200 patients and evaluated the arm lymph flow on 50 patients. The average age was 55.1 years old. The average tumor size was 2.4 cm. The average sampled number of SN was 2.3. The arm lymph channels were observed at 10 minutes after injection. They were divided into four directions: around and above the axillary vein (64%), the axilla (12%), the supraclavicule (8%), and the lateral chest (16%). The connection between the breast and the arm channel was observed in each five groups of axillary nodes shown by 3D-CT LG. We could detect their position on the axillary lymphatic mapping by 3D-CT LG during surgery. The selective axillary dissection can be performed by avoiding the arm lymph channel. Conclusions: The arm lymph channel can be observed by 3D-CT LG with the arm enhancement, which will help the selective axillary dissection to prevent the arm lymph edema.
The impact of breast reconstruction on the decision to undergo contralateral prophylactic mastectomy.
Authors: L. J. McGhan, B. A. Pockaj, R. J. Gray, S. P. Bagaria, S. A. McLaughlin, W. J. Casey, A. M. Rebecca, N. Wasif
Journal: Journal of Clinical Oncology (2011)

96 Background: In the last decade there has been an increase in the incidence of contralateral prophylactic mastectomy (CPM) for unilateral breast cancer. Although many factors have been proposed to explain this trend, the impact of breast reconstruction on the decision to undergo CPM has not been extensively studied. Methods: A retrospective review of breast cancer patients from Surveillance, Epidemiology and End Results (SEER) registry data (2004-2008) was conducted. Characteristics of patients undergoing CPM were evaluated. Results: 71,176 patients with a diagnosis of stage I-III infiltrating ductal or lobular breast cancer underwent mastectomy for their primary lesion. Among these, 10,558 patients (15%) underwent a CPM. A significantly higher proportion of women undergoing CPM had reconstruction performed (44%) than those patients not undergoing CPM (13%), p&lt;0.001. On multivariate analysis (Table), significant variables predicting CPM included age &lt;50 years (OR 10.12), breast reconstruction (OR 3.58), and lobular histology (OR 1.41), all p&lt;0.001. Of the 12,466 patients (18%) who underwent reconstruction, 4,636 (37%) had implant reconstruction, 4,498 (36%) had tissue reconstruction, and 1,122 (9%) had combined tissue/implant reconstruction (no data for 18%). On multivariate analysis, predictors of reconstruction included age &lt;50 years (OR 20.5; CI 18.5-22.7), year of surgery (2008 vs. 2004; OR 1.60; CI 1.49-1.71), low tumor grade (OR 1.19; CI 1.13-1.25) and ER+ status (OR 1.16; 95% CI 1.10-1.23). The use of radiation therapy was associated with a lower likelihood of pursuing reconstruction (OR 0.61; CI 0.58-0.65). Conclusions: Apart from age, the factor most strongly associated with CPM is the decision to have reconstructive surgery performed. This suggests that CPM may not be purely associated with risk-reduction but also with treatment factors such as cosmesis. [Table: see text]
Clinical significance of circulating tumor cells in blood from patients with advanced or recurrent esophageal cancer.
Authors: Motomu Tanaka, Hiroya Takeuchi, Kunihiko Hiraiwa, Rieko Nakamura, Tsunehiro Takahashi, Norihito Wada, Hirofumi Kawakubo, Yoshiro Saikawa, Tai Omori, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2012)

19 Background: Circulating tumor cells (CTCs) measured by the CellSearch system in metastatic breast cancer have been reported to correlate with the response to chemotherapy. The purpose of this study was to clarify the clinicopathologic characteristics of CTCs in patients with advanced or recurrent esophageal cancer. Methods: CTCs from 35 patients with advanced or recurrent esophageal cancer were measured by this system before initiation of a new line of therapy and more than 3 weeks after initiation of therapy. Correlation between CTC counts and clinicopathologic variables was examined. Results: Of the 35 patients, 14 patients (40%) had recurrent esophageal cancer and 21 patients (60%) had primary advanced esophageal cancer. Their mean age was 65 years (range, 43 to 89 ). Of the 14 patients with recurrent esophageal cancer, measurable lesions included metastasis to lymph nodes, kidney metastasis, liver metastasis, and lung metastasis. With regard to their therapeutic effect, 1 patient (3%) obtained a complete response, 14 (40%) had a partial response, 9 (26%) had stable disease, 11 (31%) had progressive disease. Of the 15 patients with complete response and partial response, the number of CTCs diminished in 8 patients (53%). Of the 20 patients with stable disease and progressive disease, the number of CTCs increased in 16 patients (80%). The change in CTCs tended to correlate with disease progression and chemotherapeutic effect (P=0.07). The survival of patients with &gt;3 CTCs was shorter than that of patients with &lt;3 CTCs both before initiation of a new line of therapy (P=0.026) and more than 3 weeks after initiation of therapy (P=0.003). Conclusions: This study suggests that measurement of CTCs in advanced or recurrent esophageal cancer patients could be useful as a tool for predicting patients’ survival and monitoring response to cancer therapy.
Clinical Significance of Reactivation of Salivary HHV-6 and HHV-7 in Multiple Myeloma Treated with Novel Agents
Authors: Kazuhito Suzuki, Shingo Yano, Nobuyuki Kobayashi, Yoji Ogasawara, Takaki Shimada, Katsuki Sugiyama, Takeshi Saito, Shinobu Takahara, Kazuhiro Kondo, Hiroyuki Yanagisawa, Noriko Usui, Keisuke Aiba
Journal: Blood (2016)
Insomnia among elderly men and risk of prostate cancer.
Authors: Lara Sigurdardottir, Unnur Anna Valdimarsdottir, Lorelei Mucci, Katja Fall, Jennifer R. Rider, Eva S. Schernhammer, Charles A Czeisler, Lenore Launer, Tamara B. Harris, Meir J. Stampfer, Vilmundur Gudnason, Steven W. Lockley
Journal: Journal of Clinical Oncology (2012)

78 Background: While a large number of studies have reported a positive association between sleep disruption and breast cancer, little is known about its potential role in prostate cancer. Methods: Within the prospective AGES-Reykjavik cohort study, we followed 2102 men from 2002-2006 until the end of 2009. The men answered questions on sleep disturbances, which were combined in various ways to reflect onset and/or maintenance insomnia. Information on the occurrence of prostate cancer was obtained through record-linkages across the Icelandic Cancer and Causes of Death Registers. We used Cox regression models with 95% confidence intervals [CIs] to estimate age- and multivariable adjusted hazard ratios [HR] of prostate cancer by symptoms of insomnia. Results: During follow-up, 135 men (6,4%) were diagnosed with prostate cancer. Compared to men without insomnia, men with severe onset and maintenance insomnia and very severe insomnia were at increased risk of total prostate cancer with HR 1.9 (CI 1.2, 3.0) and 2.2 (CI 1.3, 3.8), respectively. For advanced prostate cancer, the corresponding HRs were 2.3 (CI 0.9-6.2) and 3.7 (CI 1.4-9.9), respectively. Conclusions: These data suggest that insomnia may confer an increased risk of prostate cancer. Reduced melatonin levels represent a plausible biological explanation, although additional studies using biomarkers and longer follow-up times are needed to further clarify the underlying mechanisms.
The responsiveness of intrinsic subtypes to adjuvant anthracyclines versus nonanthracyclines in NCIC.CTG MA.5 randomized trial.
Authors: M. C. U. Cheang, D. Voduc, D. Tu, S. Jiang, S. Leung, S. K. L. Chia, L. E. Shepherd, M. N. Levine, K. I. Pritchard, T. Vickery, S. Davies, I. J. Stijleman, C. Davis, J. S. Parker, M. J. Ellis, P. S. Bernard, C. M. Perou, T. O. Nielsen
Journal: Journal of Clinical Oncology (2011)

1032 Background: Recent studies have suggested that intrinsic breast cancer subtypes may differ in their responsiveness to specific chemotherapy regimens. We assigned intrinsic subtypes to breast tumors from NCIC.CTG MA.5, a clinical trial that randomized node positive women to CMF (cyclophosphamide-methotrexate-5FU) vs. CMF (cyclophosphamide-epirubicin-5FU), and examined the differential response to adjuvant anthracycline chemotherapy. Methods: The intrinsic subtype was obtained from 476 tumors using the qRT-PCR PAM50 gene expression test. Tumors were classified into Luminal A, Luminal B, HER2-enriched (Her2-E), Basal-like and Normal, and correlated with relapse-free (RFS) and overall survival (OS). Survival was estimated using Kaplan-Meier method. Multivariable Cox regression analyses were used to determine the significance of the interaction between treatment and intrinsic subtypes, adjusted with standard clinicopathological variables. Results: Intrinsic subtypes were significantly associated with RFS (p=0.0005) and OS (p<0.0001) on the entire cohort. The HER2-E subtype demonstrated the greatest benefit from CEF vs. CMF, with an absolute difference of more than 20% in both 5-yr RFS and OS, while there was a <2% difference for the non-HER2-E tumors (interaction p = 0.03 for RFS and 0.02 for OS). Within tumors defined clinically as Her2+ by immunohistochemistry or FISH, 79% (72/91) were classified as the HER2-E subtype by genomics and these tumors were also significantly associated with better response to CEF vs. CMF (62% vs. 22%, p = 0.0006). In contrast, Basal-like tumors (n = 94) did not benefit from the substitution of methotrexate for epirubucin with an HR of 1.1 for RFS and 1.3 for OS in favor of methotrexate but the test for interaction was not significant. Conclusions: Across the intrinsic subtypes, HER2-E assignment strongly predicted anthracycline-sensitivity; furthermore, the benefit of anthracyclines is greatest in tumors that are both clinically Her2+ and Her2-E. Strikingly, the chemotherapy-sensitive Basal-like tumors showed no benefit for CEF, suggesting that non-anthracycline regimens should be further investigated in this subtype.
Hyperthermic intraperitoneal chemotherapy following gastrectomy for the prevention of carcinomatosis in advanced gastric cancer: Nonrandomized phase II prospective trial.
Authors: Satoshi Murata, Hiroyuki Naito, Hiroshi Yamamoto, Tsuyoshi Yamaguchi, Tohru Miyake, Eiji Mekata, Tomoharu Shimizu, Hisanori Shiomi, Shigeyuki Naka, Hiromichi Sonoda, Tsuyoshi Mori, Hiroya Akabori, Yuki Kawai, Hirotomi Cho, Yoshihiro Kubota, Tomoko Umeda, Yoshihiro Endo, Hajime Abe, Yoshimasa Kurumi, Tohru Tani
Journal: Journal of Clinical Oncology (2012)

116 Background: About half of patients with serosa-invasive gastric cancer develop peritoneal recurrence and die of this disease even if curative resections performed. This prospective phase II study was performed to assess the efficacy and safety of hyperthermic intraperitoneal chemotherapy (HIPEC) with three anticancer drugs in patients with curative resection of clinically T3 or T4 serosa-invasive advanced gastric cancer. Methods: Patients age 75 years or younger with curative resection of clinically T3 or T4 advanced gastric cancer were eligible for this nonrandomized phase II trial. After the curative resection of gastric cancer with D2 lymph node dissection, HIPEC was carried out for 30 minutes with 50mg of CDDP, 10mg of MMC, and 1000mg of 5-FU in 5 L saline maintained at 42-43C°. Patients were given an adjuvant S-1 treatment after surgery. Primary endpoint of this study was overall survival. Second end points included safety and recurrence rate. Results: A total of 50 patients were eligible between January 2002 and December 2010. Pathologically, 12 patients had sub-serosal invasion (pT2(ss)), 35 patients had serosal invasion (pT3), and 3 patients had adjacent organ invasion (pT4). Median follow-up period was 52 months (12-104 months). Overall 5-year survival rate in all eligible patients was 89.9%. Overall 5-year survival rate in patients with stage IB (n=4), stage II (n=12), stage IIIA (n=18), or stage IIIB (n=16) was 100%, 100%, 90.9%, or 76.2%, respectively. Only one patient (2.0%) had peritoneal recurrences. Four patients (8.0%) with pN2 had lymphatic recurrences. A total of 13 patients had postoperative complications such as minor pancreatic fistula (Grade A) (10.0%), abdominal abscess (4.0%), leakage of the anastomosis (8.0%), and pneumonia (6.0%). All patients recovered without any surgical interventions. None of patients needed for the treatment in the Intensive Care Units after HIPEC. Conclusions: Intra-operative HIPEC with three anticancer drugs following curative resection of advanced gastric cancer improves overall survival with an inhibition of peritoneal recurrence and an acceptable morbidity.