tbuckley/cabot-search huggingface dataset:
Ethnicity and clinical outcome for advanced epithelial ovarian cancer patients treated by standard cisplatin/paclitaxel chemotherapy: A combined analysis of gynecologic oncology group clinical trials
Authors: J. H. Farley, C. Tian, G. S. Rose, C. L. Brown, J. I. Risinger, G. L. Maxwell
Journal: Journal of Clinical Oncology (2008)

5573 Background: SEER analysis over the past 30 years indicates that Black patients with advanced stage epithelial ovarian cancer have decreased five-year survival compared to White patients. The purpose of this study was to confirm whether a racial disparity exists between Black and White women with ovarian cancer who are subjected to standardized surgery and chemotherapy, and to identify factors associated with administration of adjuvant treatment that have an impact upon survival. Methods: A retrospective review of 97 Black women and 1392 White women with FIGO Stage III/IV ovarian carcinoma was performed. All patients received paclitaxel combined with cisplatin while participating in one of seven Gynecologic Oncology Group (GOG) clinical trials. Treatment parameters that were reviewed included: relative dose (RD), the ratio of actual to expected dose; relative time (RT), the ratio of actual to expected duration; and relative dose intensity (RDI), the ratio of relative dose to relative time. The treatment parameters and outcomes were compared between Black and White patients. Results: Most (87%) of patients completed six cycles of chemotherapy required by the protocols and there were no differences in the number of cycles, or in RD, RT, RDI received for Black and White patients. However, Blacks showed less Grade 3–4 adverse effects concerning leukopenia (53% vs. 63%, p<0.05) and gastrointestinal toxicity (10% vs. 19%, p<0.05) than Whites. Three clinical factors were associated with treatment incompletion: poor performance status, age ≥ 70 years, and mucinous histology. There was no difference in PFS and OS between the two groups. The median PFS was 16.2 months for Black patients and 16.1 months for White patients, and the median OS was 37.9 months and 39.7 months, respectively (p>0.05 for all). The results were consistent when adjusted for important clinical factors. Conclusions: There is no difference in clinical outcome between Black and White patients when they are treated equally in a clinical trial setting. Nonetheless, Black patients may be more tolerant of platinum-based chemotherapy with less toxicity than White patients. No significant financial relationships to disclose.
Phase II/III trial of induction chemotherapy (ICT) with cisplatin/5-fluorouracil (PF) vs. docetaxel (T) plus PF (TPF) followed by chemoradiotherapy (CRT) vs. CRT for unresectable locally advanced head and neck cancer (LAHNC)
Authors: R. Hitt, J. Grau, A. Lopez-Pousa, A. Berrocal, J. Sastre, J. Belon, Y. Escobar, J. Carles, H. Cortes-Funes, J. Cruz
Journal: Journal of Clinical Oncology (2005)

5578 Background: Induction chemotherapy plus CRT vs. CRT as front line treatment have not been compare in LAHNC in randomised study. Recently, Zorat et al reported benefit in survival in patients with unresectable HNC treated with ICT (JNCI, vol 96 2004), however the optimal schedule for this approach have not been established, being TPF better than PF as neoadjuvant (Vermorken et al ASCO 2004.) Methods: Eligible pts included: unresectable tumors, measurable disease, adequate organ function, ECOG 0–1. Pts were stratificated according primary tumor site. Treatment: PF: P100 mg/m2 day(d) 1, then F 1000 mg/m2 CI d1–5 q 21d; TPF: docetaxel 75 mg/m2 d1, P 75 mg/m2 d1, F 750 mg/m2 CI d 1–5 q 21 d plus G-CSF and ciprofloxacin, by 3 cycles in both arm and then CRT. Chemoradiotherapy: conventional RT up to 70 Gy plus P 100 mg/m2 d 1–22-43. Surgery before or after CRT (neck dissection) was allowed. The objective for phase II was evaluate the 3 regimens in terms of efficacy, expecting to find difference up to 15% in favour of TPF. Planned sample size was of 120 pts. For phase III the primary endpoint is progression free survival, using a 5% 2-sided test. Results: Currently 170 pts were accrued. Pts/tumor characteristics (ECOG, age, primary site, T/N stage) were well balanced, being the majority of the pts T3–4, N2–3 and oropharynx site. Toxicity (G3/4 NCI by pts): TPF neutropenia: 25%, febrile neutropenia(FN): 25%, non-hematological toxicity (NHT): 47%; toxic death: 7%. PF neutropenia 25%, FN: 3%, NHT: 31%, toxic death: 5%. CRT: neutropenia 24%, FN 3%, NHT: 52%, toxic death: 7%. Response: Complete Response TPF: 36% plus CRT: 80%; PF 36% plus CRT 88%; CRT 47%. Conclusions: Induction chemotherapy plus CRT is feasible and more active than CRT as front line in unresectable LAHNC. Until now both schedule of induction are similar in term of efficacy. No significant financial relationships to disclose.
Phase I trial of temozolomide, thalidimide, and lomustine in patients with metastatic melanoma in the brain.
Authors: N. E. Papadopoulos, W. Hwu, S. Cain, L. Posada, K. B. Kim, J. Homsi, A. Y. Bedikian, M. A. Davies, P. Hwu
Journal: Journal of Clinical Oncology (2011)

8571 Background: Temozolomide (TMZ) and Lomustine (CCNU) are alkylating and active cytotoxic agents for metastatic melanoma (MM). The DNA repair enzyme O6-alkylguinine-DNA alkyltransferase (ATase), is the major cause of drug resistance for alkylating agents. Depletion of ATase by continuous dosing of TMZ may improve the anti-tumor activity of alkylating agents. This Phase I study is designed to establish a safe and tolerated regimen of oral cytotoxic agents, TMZ and CCNU in combination with a cytostatic agent, thalidomide (TLD), in patients with MM in the brain. Methods: Patients (pts) with stage IV MM in the brain with or without extracranial metastasis were entered successively onto 3 treatment cohorts: level 1, CCNU 30 mg/m2on day 1; level 2, CCNU 45 mg/m2on day 1; level 3, CCNU 60 mg/m2 on day 1. CCNU was administered at a flat dose of 30 mg/m2 on day 29 for all cohorts. TMZ was administered at 75mg/m2/d x 6 weeks followed by a 2-week break. TLD was administered at 200 mg/m2/d to the first 3 patient in level 1, then 200 mg/d in all other patients. Safety was assessed at weeks 2, 4, 6, 8 and every 4 weeks thereafter; tumor response was evaluated every 8 weeks. Results: Seventeen pts were enrolled, 7 pts each in levels 1 and 2, and 3 pts in level 3. . The MTD was determined to be dose level 2: CCNU 45 mg/m2on day 1. Three pts had a deep venous thrombosis. The most common adverse events were fatigue, constipation and myelosuppression. Of 16 pts assessable for disease response: 2 experienced a partial response, 2 stable disease and 2 mixed response. Disease response in brain and visceral organs were observed in dose levels 1 and 2. Conclusions: The combination therapy of TMZ, TLD and CCNU is safe and well tolerated in patients with MM in the brain. Clinical activity was seen at both levels 1 and 2. Further study of this oral drug combination therapy in these patients with extremely poor prognosis and lack of effective therapy is warranted.
Outcomes of preoperative chemotherapy in bladder cancer patients including node-positive disease.
Authors: Bishoy Faltas, Pravin R. Date, Douglas Scherr, Daniel P. Nguyen, Bashir Al Hussein Al Awamlh, Padraic O'Malley, Paul J. Christos, Himisha Beltran, David M. Nanus, Scott T. Tagawa
Journal: Journal of Clinical Oncology (2015)

370 Background: Neoadjuvant chemotherapy is associated with improved overall survival benefit and the concept of systemic therapy followed by local consolidation may also lead to favorable long-term outcomes for those with lymph node (LN) metastases at presentation. Our goal was to examine the outcome of preoperative chemotherapy in patients (pts) with and without clinical evidence of LN metastases. Methods: After informed consent, patients were enrolled in a prospective database prior to radical cystectomy with lymph node dissection for bladder cancer between December 2001 to February 2014. Data were analyzed using descriptive statistics. Results: Our cohort included 63 patients receiving pre-operative chemotherapy with a median age 68 (range 38-91), 46 (72%) were male, and 17 (27%) had gross metastatic disease to lymph nodes (LNs). 13 pts received MVAC (20%), 44 gemcitabine and cisplatin (GC) (69%), 1 gemcitabine and carboplatin, 1 received ifosfamide, paclitaxel, and cisplatin and 4 pts had unknown neoadjuvant chemo outside of the institution. Most patients with LN positive (71%) disease received GC preoperative regimens. The median and the modal number of cycles were 4 (range 1-6). 44 patients underwent robotic-assisted radical cystectomy (RARC) (69%), 19 underwent open radical cystectomy (30%), and another pt. had RARC converted to an open procedure. Overall, 20 (31%) patients achieved pathologic complete response (pCR). Four pts (24%) with initial metastatic disease achieved pCR after preoperative chemotherapy. Overall pCR rates were similar between MVAC (38%) and GC (33%). All LN positive patients who achieved pCR had received gemcitabine-cisplatin preoperatively and underwent RARC. Recurrence-free and overall-survival data will be presented at the meeting. Conclusions: Preoperative chemotherapy was associated with a significant pCR rate in all bladder cancer patients including LN positive patients.
Circulating levels of RANK/RANKL and OPG in patients with bone metastasis treated with zoledronic acid: A prospective study.
Authors: T. Ibrahim, L. Mercatali, E. Sacanna, R. Ricci, E. Scarpi, P. Serra, F. Fabbri, C. Tison, D. Amadori
Journal: Journal of Clinical Oncology (2011)

10611 Background: Bone metastases are the most frequent malignant disease of the bone and are responsible for high morbidity and reduced quality of life in cancer patients. Zoledronic acid (Zometa, Zol), routinely used in this subgroup of patients, inhibits bone resorption and has antitumor properties. It has also been reported to have an antiangiogenic effect. Methods: The study prospectively evaluated the levels of RANK, RANKL and OPG transcripts by real-time PCR in the peripheral blood of 49 consecutive patients with advanced breast, prostate or lung cancer (36, 7 and 6, respectively). Patients were eligible if they were at first diagnosis of bone metastases and if they had not previously undergone treatment with bisphosphonates. All patients received the standard Zol schedule of a 4-mg infusion every 28 days. Patients were monitored for about 12 months and blood samples were collected before the first infusion of Zol and every 4 months thereafter. Results: At least 3 blood samples were taken from all 49 patients (4 samples were taken from 29). Baseline RANK, RANKL and OPG median values were 78.3 (range 7.3-620.6), 319.1 (21.4-1884.4) and 1.52 (0.1-58.0), respectively. At 12 months RANKL median value had decreased by 22% with respect to baseline, whereas OPG median value had increased by about 96%. Consequently, the RANKL/OPG ratio decreased by 56% with respect to baseline. These differences, however, did not reach statistical significance, perhaps due to the small case series evaluated. Conversely, although RANK median values had increased by 36% at 8 months with respect to baseline, they had returned to near baseline values at 12 months. OPG, RANK and RANKL/OPG trends were significantly related. Conclusions: The present work is one of the few prospective studies to be carried out on circulating markers that are potentially correlated with bone metastases. It was observed that markers of the RANK/RANKL/OPG pathway in the peripheral blood of bone metastasis patients were probably modulated by Zol treatment. Zoledronic acid would appear to decrease osteoclast activity both directly and also via RANK/RANKL/OPG pathway modulation. Further investigation of the biological results is warranted.
Anaplastic large-cell lymphoma and breast implants: Results from a structured expert consultation process.
Authors: B. Kim, C. Roth, V. L. Young, K. C. Chung, K. van Busum, C. Schnyer, S. Mattke
Journal: Journal of Clinical Oncology (2011)

e18535 Background: There are concerns about a possible association between anaplastic large cell lymphoma (ALCL) and breast implants. We conducted an evidence review and a structured expert consultation process on ALCL and breast implants. Methods: We recruited a multidisciplinary panel to participate in a structured expert consultation process to evaluate the evidence for the association, its clinical significance, and a potential biological model based on their interpretation of the published evidence. The process involved a systematic literature review, development of 65 statements related to ALCL and breast implants, and two rounds of panelists’ ratings of the statements integrated with a face-to-face discussion. Data from the final ratings were synthesized and analyzed. Results: Panelists agreed that (1) there is a positive association between breast implants and ALCL development but likely under-recognition of the true number of cases; (2) a recurrent, clinically evident seroma occurring ≥ 6 months after breast implantation should be aspirated and sent for cytologic analysis; (3) anaplastic lymphoma kinase (ALK)-negative ALCL that develops around breast implants is a clinically indolent disease with a favorable prognosis that is distinct from systemic ALK-negative ALCL; (4) management should consist of removal of the involved implant and capsule, which is likely to prevent recurrence, and evaluation for other sites of disease; and (5) adjuvant radiation or chemotherapy should not be offered to women with capsule-confined disease. Little agreement, however, was found regarding etiologic risk factors for implant-associated ALCL. Conclusions: Our assessment yielded consistent results on a number of key issues regarding ALCL in women with breast implants, but substantial further research is needed to improve our understanding of the epidemiology, clinical aspects, and biology of this disease.
Association of CD133 expression levels with the k-ras mutation status in rectal cancers before and after preoperative radiochemotherapy.
Authors: Thilo Sprenger, Jochen Gaedcke, Lena-Christin Conradi, Peter Jo, Klaus Jung, Tim Beissbarth, Kia Homayounfar, B. Michael Ghadimi, Torsten Liersch
Journal: Journal of Clinical Oncology (2013)

400 Background: The role of the potential stem cell marker CD133 as a predictive or prognostic marker in multimodal rectal cancer treatment is currently under debate. While CD133 has been identified as a prognostic marker in rectal cancers after preoperative radiochemotherapy (RCT) it was recently characterized as a very unspecific feature for colorectal cancer stem cells. We therefore analyzed the association between CD133 expression and mutations in the proto-oncogenes K-Ras and PI3K in rectal cancer patients receiving neoadjuvant RCT. Methods: CD133 expression was evaluated immunhistochemically in pre-treatment biopsies and surgical specimens of 128 patients with locally advanced rectal cancers (cUICC II/III) treated with preoperative RCT within the phase-III German Rectal Cancer Trials. K-Ras mutations were analyzed by sequencing of exons 1, 2, and 3. PI3K mutations were detected by sequencing the p110α subunit (PIK3CA) and correlated with histopathologic parameters, tumor regression and survival. Results: CD133 expression was significantly associated with mutations in the K-Ras gene in both pre-treatment biopsies and post-treatment tumor specimens in uni- and multivariate analyses. However, no significant correlation was observed between CD133 and PI3K mutations. Post-treatment CD133 levels were correlated with neoadjuvant RCT (50.4 Gy/5-FU vs. 50.4 Gy/5-FU+Ox) and tumor regression grading. Anyway, there was no significant association between pre- and post-treatment CD133 expression and disease-free survival. Conclusions: CD133 expression levels are strongly associated with mutations in the K-Ras proto-oncogene in rectal cancers before and after preoperative RCT. Our results strengthen the hypothesis that CD133 is not a specific marker for colorectal stem cells but might be integrated in proliferation pathways like the ras-raf axis.
Sunitinib-associated hypothyroidism in patients with metastatic renal cell carcinoma.
Authors: Satinder Jagdev, Kate Hayward, Sheryl Sim
Journal: Journal of Clinical Oncology (2013)

443 Background: Sunitinib (sun) treatment for patients (pts) with metastatic renal cancer (mRCC) can often lead to fatigue. The incidence of sun-induced hypothyroidism (HT) in the phase III pivotal study of pts with mRCC was 14% for all grades and 2% for grades 3-4. Subsequent retrospective and prospective studies described incidences of between 30–85%. Elevated TSH alone may be seen in up to 85% of mRCC pts treated with sun. Symptoms of HT, eg: fatigue, constipation, cold intolerance, hair thinning, and dry skin have been reported in the majority of sun-treated pts. Methods: We reviewed of all cases of mRCC pts initiating sun treatment between January 2008 and December 2009 using the electronic record system Patient Pathway Manager. Pts with underlying HT, abnormal TFTs at baseline or those on sun for less than two cycles were excluded. TFTs were performed at baseline and then day 1 of every two cycles. Response was assessed every 2-3 cycles. The aims of the study were to Identify rate of sun-induced HT in St James’s Institute of Oncology and determine whether there is a correlation between HT and disease response. Results: 84 pts were included (median age 62 years). 90% had good or intermediate prognosis disease by Memorial Sloane-Kettering Cancer Centre (MSKCC) criteria. 52 pts had TSH &lt;6mU/L and 32 had TSH of &gt;6mU/L. Progression-free survival was significantly longer in those pts with TSH of &gt;6mU/L (29.6 months) compared to those with TSH &lt;6mU/L (11.3 months). Conclusions: Sun-induced HT occurred in approximately 30% of pts and predicted for improved progression-free survival. Further studies are needed to characterise this and updated data will be presented.
Use of HER2 gene amplification to identify patients with metastatic colorectal cancer resistant to anti-EGFR monoclonal antibodies.
Authors: Cecilia Barbara, Vittoria Martin, Francesca Molinari, Lorenza Landi, Alice Riva, Piercarlo Saletti, Sara de Dosso, Ravit Geva, Sabine Tejpar, George Fountzilas, Konstantine T. Kalogeras, Milo Frattini, Federico Cappuzzo
Journal: Journal of Clinical Oncology (2012)

474 Background: KRAS mutation represents the only validated biomarker used in clinical practice for selection of metastatic colorectal cancer (mCRC) candidates for therapy with the anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibodies. Previous studies conducted in small cohorts of patients suggested that HER2, the major EGFR partner, could modify the sensitivity to anti-EGFR agents. Aim of the present study was to investigate the role of HER2 gene status in a cohort of mCRC patients treated with cetuximab or panitumumab. Methods: 266 chemorefractory mCRC patients treated with cetuximab or panitumumab alone or in combination with chemotherapy were collected in an international consortium effort. HER2 gene status was analyzed using the dual-color FISH assay LSI HER2/neu-CEP17 (PATHVYSION, Abbott) in one central lab, whereas KRAS/BRAF mutations were investigated locally. HER2 gene amplification was defined as the presence of a ratio between HER2 gene and chromosome 17 centromere &gt; 2. Results: An objective response to anti-EGFR therapy (complete or partial response according to RECIST criteria) was observed in 79/266 (29%) of patients. Twelve cases (4.5%) showed the classical pattern of HER2 gene amplification (R&gt;2) in the whole tissue (&gt;80% of tumor cells). By matching HER2 gene status with clinical response we observed that HER2 gene amplification was significantly related to therapy resistance (p&lt;0.0001). Moreover, analysis of follow-up data indicated that HER2 gene amplification was significantly associated with a worse progression free survival (PFS, p=0.0025) and with a trend for a worse overall survival (p=0.062). Similar associations were also observed in the KRAS/BRAF wild-type patients. Conclusions: Data from this large retrospective study suggest that HER2 gene status evaluated by FISH may represent an additional marker useful for the prediction of mCRC patients’ response to EGFR-targeted therapies, in line with very recent evidence. In particular, patients with HER2 gene amplification seem to be resistant and show a shorter PFS. Future studies are needed to deeply investigate the clinical and biological meaning of HER2 gene status deregulation in mCRC.
Diagnosis of malignant pleural mesothelioma: Comparison between pleural effusion cytology and pleural biopsy.
Authors: S. Matsumoto, K. Yoneda, H. Orui, M. Hashimoto, T. Takuwa, Y. Okumura, N. Kondo, I. Torii, T. Tsujimura, K. Fukuoka, T. Nakano, F. Tanaka, S. Hasegawa
Journal: Journal of Clinical Oncology (2011)

e21095 Background: Pleural effusion cytology is sometimes insufficient to diagnose Malignant Pleural Mesothelioma (MPM) and pleural biopsy is essential for definitively diagnosis. In this study, we analysis pleural biopsy and pleural effusion cytology. Methods: Patients suspected of MPM who underwent pleural biopsy under general anesthesia between February 2004 and December 2010 were included in this study. Pleural biopsy was performed through a 3 cm skin incision on the supposed skin incision line of extrapleural pneumonectomy (EPP). A stamp-sized (4×3 cm) specimen including all layers of the parietal pleura was collected. It contains not only nodule but normal pleura. Results: One hundred forty five patients underwent pleural biopsy. 80 patients were diagnosed as MPM (55 epithelioid, 7sarcoma, 8 desmoplastic, 5 biphasic, 1 anaplastic, 4 unknown), 5 lung cancer, 1 lymphoma, 1 invasive thymoma, 1 synovial sarcoma and 1 malignant pleural tumor. Among 80 MPM patients, 50 cases also underwent pleural effusion cytology. Fourteen cases were pleural effusion cytology negative/pleura biopsy positive. The ratio of pleural effusion cytology negative is higher in desmoplastic type than epithelioid type (P<0.05). Conclusions: Sampling full thickness and enough size of parietal pleura is essential to achieve a definitive diagnosis of MPM. The results of pleural effusion cytology and pleural biopsy are sometime discrepant, especially in desmoplastic or sarcoma type.