tbuckley/cabot-search huggingface dataset:
Use of VEGFR1 expression in benign pelvic lymph nodes to predict biochemical recurrence in patients with high-risk prostate cancer.
Authors: Sumanta Kumar Pal, Wang Zhang, Jiehui Deng, Yong Liu, Karen L. Reckamp, Xueli Liu, Rebecca A. Nelson, Timothy G. Wilson, Clayton Lau, Hua Yu, Robert A. Figlin
Journal: Journal of Clinical Oncology (2012)

205 Background: High-risk prostate cancer (PCa) is a heterogeneous disease, and biomarkers that accurately predict clinical outcome within this subset are lacking. The pre-metastatic niche (PMN) represents one possible biomarker—this harbinger of future metastasis may be characterized by infiltration of VEGFR1 + cells [Kaplan et al Nature 139:820, 2005]. Given the predilection of PCa to spread to nodal sites, the association between VEGFR1 expression in benign pelvic lymph nodes and clinical outcome was examined. Methods: The City of Hope Prostate Cancer Registry (COH PCR) was used to identify 46 patients with high-risk PCa (baseline PSA &gt; 20, pT3a-4 disease, or biopsy Gleason 8–10) who had undergone radical prostatectomy and pelvic lymph node dissection (PLND). The COH PCR prospectively collects clinical data associated with patients undergoing prostatectomy at the institution, and warehouses available clinical specimens. Benign tissue specimens derived from PLND were acquired for each patient, and were stained for VEGFR1 expression. VEGFR1 + cell clusters were counted within 8 distinct 40x fields, and the cluster count was averaged. Results: VEGFR1 + clustering in benign PLND specimens was a significant predictor of biochemical recurrence on multivariate Cox proportional hazards analysis, and outperformed other variables including established prognostic factors such as age, extracapsular spread, seminal vesicle invasion, and the aforementioned high-risk features. Patients with increased VEGFR1 + clustering pelvic lymph node tissue had a shorter interval to biochemical recurrence (HR 0.18, P&lt;0.10). Conclusions: These preliminary results indicate that increased VEGFR1 + cell clustering in benign nodal tissue may predict poorer clinical outcome in patients with high-risk PCa. VEGFR1 + cells (a purported constituent of the PMN) represents a targetable entity. A randomized, phase II study employing axitinib (VEGFR1 IC 50 =1 nM) as neoadjuvant therapy in patients with high-risk PCa is nearing initiation at City of Hope ( NCT01385059 ).
Survival of lung surgery patients with pulmonary metastases from colonic neoplasms
Authors: M. Tampellini, I. Alabiso, A. Ottone, S. Miraglia, L. Forti, E. Bertona, C. M. Sculli, E. Bellini, O. Alabiso, L. Dogliotti
Journal: Journal of Clinical Oncology (2008)

15039 Background: Resection of liver mts has been repeatedly shown to prolong survival of pts with metastatic colorectal cancer (mCRC). While in some published data resection of lung mts (RLM) seems to be equally advantageous, a comparison between outcomes of resected vs non resected pts has never appeared. Methods: We collected data from 706 mCRC pts treated in 2 different institutions from 1994 to 2007. We selected data from 214 pts (30.3%) with lung mts at first diagnosis of mCRC which were grouped as follows: G1) 148 pts with lung and extra-lung mts; G2) 29 pts with lung as unique site of mts not submitted to RML; G3) 28 pts submitted to RML and subsequent adjuvant chemotherapy; G4) 9 pts submitted to neoadjuvant chemotherapy prior to surgery. Results: Patients’ characteristics were: median age (range) yrs: 63.3 (31.1–80.6); male/female 133/81; stage at diagnosis (A/B/C/D/UNKN) 13/22/73/102/4; site of primitive: rectum/left colon/right colon 75/91/48; site of mts: liver/lung/other: 128/214/114. Chemotherapy administered were: 1 pts Triplet, 168 pts Doublets (LOHP-based 144, CPT11-based 24); 45 pts 5FU or oral fluoropyrimidines only. Response rates were: overall 80/214 (37.4%); G1 50/148 (33.8%); G2 14/29 (48.3%); G3 not applicable; G4 7/9 (77.8%). Surgery was performed in 37/214 pts (17.3%). No surgery mortality was recorded. Time to progressions (TTP) were (mos): 13.5, 11.6, 13.1, 20.4, 27.9 Overall, G1, G2, G3, and G4, respectively (p<0.0001). Considering only pts with lung as unique site of mts (G2 non resected vs G3+4 resected), TTPs were 13.1 vs 24.1 mos (p<0.001). Overall survivals (OS) were (mos): 29.6, 23.8, 31.2, 67.2, 59.5+ for Overall, G1, G2, G3, and G4, respectively (p<0.00001). Considering only pts with unresected lung mts (G2) vs resected lung mts (G3+G4), OSs were 31.2 vs 71.2 mos (p<0.0001). Conclusions: Although in the presence of pts selection bias typical of retrospective studies, our comparative data showed that: 1) resection of lung mts is safe, confirming previous reports; 2) resected patients presented a longer TTP and OS than non resected ones; 3) chemotherapy administration before or after surgery did not seem to be different in terms of OS, even though neoadjuvant therapy might help clinicians to select those pts with a more indolent form of the disease. No significant financial relationships to disclose.
Predictors of recurrence in stage I/II colorectal cancer: Analysis of a single institution’s experience for over 24 years.
Authors: Miguel Gonzalez Velez, Narjust Duma, Larysa Jessica Sanchez, Ramya Undamatla, Jose Ruiz Mino, Martin Gutierrez
Journal: Journal of Clinical Oncology (2016)

534 Background: Surgical resection remains a mainstay of treatment for localized colorectal cancer (CRC). However, up to 35% of patients (pts) develop recurrence with a significant decrease in overall survival. The aim of this study was to evaluate clinical characteristics and specific predictors of recurrence for stage I/II CRC Methods: We performed a retrospective analysis of 2310 pts diagnosed with stage I/II CRC at our institution between 1990 and 2013, with a minimum follow up of 24 months. Tumor characteristics and recurrence data were studied. Cox regression was used for statistical analysis. Results: Of the 2310 pts, recurrence was identified in 276 (12%) pts, of which 88 (32%) pts had early recurrence ( &lt; 1 year). Median time of recurrence was 625 days. 210 (76%) pts had local recurrence while 66 (24%) pts had distal recurrence, with liver being the main site of distant metastasis. Males had a higher recurrence rate than females (16% vs. 7%, p &lt; 0.0001). When comparing recurrence pts (R) with non-recurrence (NR) pts, Hispanics were more prevalent in the R group (13% vs 8%, p &lt; 0.01). R pts were more likely to have rectal and poorly differentiated tumors (33% vs. 13%, p &lt; 0.0001; 23% vs. 14%, p &lt; 0.0001, respectively). Mucinous adenocarcinomas were more prevalent in the R group (16% vs. 9%, p &lt; 0.0005). In multivariate analysis: male sex (OR: 1.24, 95% CI: 1.21-1.56, p &lt; 0.001), rectal tumors (OR: 4.2, 95% CI: 3.14-5.06, p &lt; 0.001), tumor size (OR: 2.55, 95% CI: 1.31-4-51, p &lt; 0.01), and positive margins (OR: 3.6, 95% CI: 2.13-5.21, p &lt; 0.04) were independent predictors for recurrence. K-ras (+) status was a predictor of recurrence by univariate analysis. Age, race, and histologic grade were not predictors of recurrence. Pts with early recurrence had a lower median overall survival compared to pts that developed recurrence after 1 year, 37 months (95% CI: 26.6-49.6) vs. 59 months (95% CI: 42.4-74.3), p &lt; 0.04. Conclusions: Pts with recurrence were more likely to have rectal and poorly differentiated tumors. Poorer survival was observed in pts with early recurrence. These findings could serve as important prognostic information and may help identify the pts that would benefit from aggressive surveillance after treatment.
Bevacizumab in combination with FOLFIRI in metastatic colorectal cancer: A retrospective study of adverse events and their correlation with clinical outcome.
Authors: John Gordon Lenehan, Mary J. MacKenzie, Mark David Vincent, Stephen Welch
Journal: Journal of Clinical Oncology (2012)

426 Background: Bevacizumab is a monoclonal antibody against the VEGF ligand that disrupts vascularization of solid tumors and is part of first-line therapy for metastatic colorectal cancer (mCRC) in Ontario. The current study is intended to assess the rate of adverse events in general practice and to explore the relationship of adverse events to clinical outcomes in patients (pts) receiving bevacizumab. Methods: Patients with mCRC from one Ontario cancer centre who received FOLFIRI with bevacizumab (BEV-FOLFIRI) as first-line treatment were retrospectively reviewed. Data collected included demographics, adverse events, radiographic response, and survival times. Results: 57 patients were included in the study with a median age of 61 years, all with ECOG ≤1, and received a median of 5.5 cycles of BEV-FOLFIRI. Median follow-up was 5.8 months. Progression-free survival (PFS) was 9.8 months (95% CI 8.2-11.0) and overall survival (OS) was 13.1 months (95% CI 12.0-15.0). The most common bevacizumab-related adverse event was proteinuria with 11 (19.3%) pts developing any grade. Other adverse events included venous thromboembolism (VTE) in 9 (15.8%) pts, hypertension (NCI-CTCAE v3) in 7 (12.3%) pts, and GI perforation in 2 (3.5%) pts. 15 (26.3%) pts had a favorable radiographic response with 40% of pts who developed significant hypertension considered responders, compared with only 25% of those without hypertension. When using NCI-CTCAE v4.03, 19 (33.3%) pts developed grade ≥2 hypertension and had significantly longer PFS (13.5 vs 8.9 months, p=0.005) and OS (16.3 vs 11.0 months, p=0.015). Finally, developing a VTE was associated with increased PFS (14.8 vs 9.6 months, p=0.012), whereas proteinuria was associated with a significantly reduced OS (6.6 vs 14.0 months, p=0.001). Conclusions: Use of NCI-CTCAE v4.03 criteria for hypertension identifies more patients with significant hypertension. Patients with hypertension according to these criteria appear to have a better treatment response, suggesting hypertension may be a useful biomarker. Conversely, new or worse proteinuria related to therapy was associated with a poor treatment response.
Early tumor shrinkage under first-line tyrosine kinase inhibitor as a surrogate endpoint of overall survival in patients with metastatic renal cell carcinoma.
Authors: Hideaki Miyake, Ken-ichi Harada, Masato Fujisawa
Journal: Journal of Clinical Oncology (2016)

523 Background: The objective of this study was to assess the prognostic impact of early tumor shrinkage induced by first-line tyrosine kinase inhibitors (TKIs) on overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC). Methods: This study included a total of 185 consecutive Japanese patients with mRCC, consisting of 120 and 65 who were treated with sunitinib and sorafenib, respectively, for at least 3 months as first-line therapy. Prognostic outcomes in these 185 patients were retrospectively assessed focusing on the significance of tumor shrinkage at 12 weeks after the introduction of TKIs as a predictive factor of OS. Results: As the best responses to TKIs, 3, 40, 105 and 37 were judged to show a complete response, partial response, stable disease and progressive disease, respectively. The median progression-free survival (PFS) and OS in the 185 patients was 7.3 and 33.6 months, respectively. At 12 weeks after the introduction of TKIs, 9 patients reached a tumor shrinkage from -100 to -50%, 42 patients from -49 to -25%, 59 patients from -24 to 0%, and the remaining 70 patients had a gain of tumor size or new metastatic lesions. The median OS stratified according to tumor shrinkage at 12 weeks after the introduction of TKIs as shown above was 59.2, 39.1, 27.8 and 19.1 months, respectively. Univariate analysis identified the Memorial Sloan-Kettering Cancer Center (MSKCC) classification, Heng risk classification, C-reactive protein (CRP) level, lymph node metastasis, bone metastasis, liver metastasis, number of metastatic organs, histological subtype, sarcomatoid feature, PS and tumor shrinkage as significant predictors of OS. Of these significant factors, only the MSKCC classification, CRP level, liver metastasis and tumor shrinkage were shown to be independently associated with OS by multivariate analysis. Conclusions: These findings suggest that tumor shrinkage at 12 weeks after the introduction of TKIs was shown to have a significant impact on the OS in mRCC patients; therefore, early tumor shrinkage could be used as a reliable surrogate endpoint of OS in patients with mRCC receiving TKI as first-line agent.
Patient communication prior to initial consultation for palliative radiotherapy.
Authors: Anna Paulsson, Steve E. Braunstein
Journal: Journal of Clinical Oncology (2016)

30 Background: For patients undergoing radiation treatment for advanced cancer, coordination between multiple care teams is required. The radiation therapy care pathway is complex, with numerous components, including consultation, planning, treatment delivery, and follow up care. Fragmented care can result from suboptimal communication among referring providers and patients. Prior to initial consult with a radiation oncologist, many patients are unaware of the complex logistics, resulting in additional distress. We conducted a survey to determine how to improve communication to better prepare patients for radiation therapy. Methods: In a pilot project to address communication barriers for patients receiving radiotherapy, a brief 10-question multiple choice survey was developed to gather patient-reported data at the time of initial consultation for palliative or primary CNS radiation treatment. The survey addressed patient understanding of the indication, logistics, and expected outcomes and toxicity of radiotherapy. Results: Our preliminary data is gathered from 16 patients who filled out a survey at the time of consult. Of this group, 10 patients received palliative radiotherapy for advanced malignant disease. Ninety percent of patients were able to correctly identify the role of the radiation oncologist in cancer care. Only 30% demonstrated understanding of the logistics of radiotherapy, including details of planning and multisession treatment delivery. Several patients noted concerns about the logistics and expected efficacy of treatment. No patients were previously informed of the indication of radiotherapy for pain palliation. Conclusions: Initial survey results suggest that advanced cancer patients are often mis- or under-informed about their disease status and the indication of radiotherapy in treatment and palliation of symptoms. Improved communication with patients referred for radiation therapy consultation may alleviate their concerns and enable them to set appropriate expectations for subsequent radiotherapy, minimizing distress. Ongoing survey results will be utilized to identify opportunities to educate providers towards better patient communication.
Final results of a risk-adapted policy of adjuvant chemotherapy (ACT) in patients with invasive bladder carcinoma (IBC).
Authors: J. A. Arranz Arija, Y. Jerez Gilarranz, A. Soria Lovelle, C. López López, P. Sabin Dominguez, M. C. Riesco, J. Adeva Alfonso, D. Urosa Velasco, E. López Juárez, R. González Beca, M. Martin
Journal: Journal of Clinical Oncology (2011)

4613 Background: ACT for IBC is controversial and supported by underpowered randomized trials. Additional information from metanalysis or longitudinal studies can help to better define its role. Methods: Since 1988, our risk-adapted institutional policy for patients (p) with IBC and radical cystectomy (C), has been to inform patients about their particular risk of relapse, status of the art at that moment and toxicity of ACT. For p with pT3-4 or N+, we recommended ACT but we offered follow-up as an alternative (C), and the opposite for pT2N0. Both cohorts, C and ACT were prospectively followed according to the standard clinical practice. We present here the results of progression-free survival (PFS), overall survival (OS) and cancer-specific survival (CSS) comparing C alone vs ACT. Results: From 1988 to 2009, 491 p were registered, 309 C and 182 ACT (37%). Median follow-up was 68 m. ACT was MVAC x3 (90 p) CIS-GEM x4 (80 p) or Carbo-GEMx4 (12 p). There were no toxic deaths. Mean age was 65 y, and 89% were male. As expected, there was an unbalance in prognostic factors favoring C vs ACT (p < .05 for all the following comparisons): age >70y (30 vs 21%); AJCC 2010 staging (pII, pIII, pIVN+: 57,3%, 33,3%, 9,4% vs 18,1%, 33%, 48,9%); histology (papillary/solid: 41%/59% vs 21%/79%), grade (G3: 92% vs 97%), surgical complications (37 % vs 27%) and period of treatment (until 1999/2000 and later: 51%/49% vs 36%/64%). Despite this, there were no significant differences in crude PFS, OS or CSS, suggesting an effect of ACT. This effect could be demonstrated in a multivariate Cox model adjusted by the unbalanced variables. Table shows the hazard ratio (HR) of relapse and death (ACT/C). Due to interaction between stage and treatment, results are presented stratified by pathological stage. Conclusions: In our series of IBC, ACT was associated with a statistically significant reduction in the risk of relapse and death in patients with extravesical extension (pIII) or N+ (pIV). PFS CSS OS HR IC 95% HR IC 95% HR IC 95% Unadjusted 1.23 0.95–1.60 1.13 0.85–1.49 0.99 0.77–1.26 Multivariate pII 1.15 0.62–2.12 1.04 0.52–2.10 0.90 0.50–1.60 pIII 0.50 0.30–0.84 0.54 0.32–0.91 0.48 0.31–0.76 pIV 0.30 0.17–0.52 0.25 0.13–0.47 0.24 0.13–0.43
Characteristics and outcomes of advanced cancer patients referred to outpatient supportive care who missed their appointment.
Authors: Marvin Omar Delgado-Guay, Silvia Tanzi, Maria Teresa San-Miguel, Janet L. Williams, Julio Allo, Gary B. Chisholm, Eduardo Bruera
Journal: Journal of Clinical Oncology (2013)

e20612 Background: Supportive Care Outpatient Clinics (SCOC) offer comprehensive care and symptom management to patients with advanced cancer (AdCa). Missed appointments (MA) are frequent but they are no studies on the clinical outcomes of patients who fail to show for consultation. Methods: We determined the frequency of MA, including clinical and demographic data, and reviewed clinic appointment records for 218 consecutive kept (KA) and 218 MA for distinct patients referred to SCOC from January to December 2011. Results: 218/1,352 (16%) AdCa who were referred to our SCOC, missed their appointment. The median age was 57 years (interquartile range 49-67). The mean (range) time between referral and appointment was 7.4 days (0-71) for KA vs. 9.1 days (0-89) for MA (p=0.0062). Age, gender, marital status, and cancer types or stages, and reasons for referral to SCOC were not significantly different between MA and KA patients. African Americans had more MA 49/218 (22%) vs. 31/217 (14%), p=0.06. The reasons for MA were: admission to the hospital 17/218 (8%), death 4/218 (2%), appointment with primary oncologist 37/218 (18%), other appointments 19/218 (9%), visits to emergency room(ER) 9/218(9%), and unknown 111/218(54%). MA patients visited more the ER at 2 weeks 16/214 (7%) vs. 5/217 (2%), p=0.01, and 4 weeks 17/205(8%) vs. 8/217(4%), p=0.06. Median survival for MA patients was 177 days (range:127-215) vs. 253 days (range:192-347) for KA patients (p=0.013). Multivariate analysis showed that MA were associated to the time between referral and scheduled appointment (OR: 1.026/day, p=0.03), referral from targeted therapy services (OR:2.177, p=0.004), living at Texas/Louisiana regions (OR;2.345, p=0.002), having advanced directives (OR:0.154, P&lt;0.0001), and being referred for symptom control (OR:0.024, p=0.0003). Conclusions: AdCa with MA have worse survival and increased ER utilization. We identified AdCa at higher risk for MA who should undergo more aggressive follow up. More research on MA prevention is needed.
Survival outcome of bevacizumab followed by cetuximab in metastatic colorectal cancer patients.
Authors: Kozo Kataoka, Akiyoshi Kanazawa, Akio Nakajima, Hisahiro Hosogi, Seiitirou Kanaya, Yukihiro Kohno
Journal: Journal of Clinical Oncology (2012)

529 Background: The molecular targeted agents, such as bevacizumab and cetuximab have been shown to improve overall survival of metastatic colorectal cancer (mCRC) patients. However, we still do not know what sequence is best to use the molecular targeted agents for mCRC especially in K-ras wild case. In this analysis, we evaluate the benefits of using bevacizumab followed by cetuximab for mCRC patients retrospectively. Methods: From July 2006 to September 2010, 60 chemotherapy-naive patients who were diagnosed as mCRC, received oxaliplatin based regimen for first line, did not respond to bevacizumab containing regimen used for first line or second line, and received cetuximab or continued bevacizumab, were eligible for this analysis. 28 patients received cetuximab as third line or fourth line chemotherapy due to K-ras wild type (Group A). And 32 patients continued bevacizumab-containing regimen in spite of disease progression (Group B). Results: The median number of cycles of bevacizumab containing regimen were 9 (range, 2-30) in group A and 8 (range, 2-27) in group B, and cetuximab 12(range, 3-32) in group A. The difference of the rate of serious adverse effects was not significant between two groups. Median overall survival was significantly higher in Group A than Group B (31.2 months (95%CI: 23.2-39.3 months) and 27.0 month (95%CI: 17.2-37.6), respectively) (P&lt;0.001). Partial response rate of cetuximab was 18%(5/28) in group A. Median progression free survival of cetuximab in group A was 4.3 months (95%CI: 2.62- 6.06). Conclusions: Using cetuximab after progression with bevacizumab might be effective sequence to improve the overall survival of K-ras wild mCRC patients. But we need further prospective study to look for the best sequence in chemotherapy for mCRC patients.
A phase II study of PD-0332991 in patients with advanced hepatocellular cancer.
Authors: Susan Joy Littman, Erik S. Knudsen, Agnieszka Witkiewicz, Terry Hyslop, Nancy Lewis, Madhavan V. Pillai, Christina Brus, Edith P. Mitchell
Journal: Journal of Clinical Oncology (2013)

321 Background: Hepatocellular carcinoma (HCC) is the 5th most common cancer worldwide and the 3rd most frequent cause of cancer-related mortality. Surgical resection &amp; liver transplantation are the main curative options. Most patients present with advanced stage and poor liver function and are ineligible. Cytotoxic drugs give poor response rates and little benefit. The MKI sorafenib has been shown to significantly increase PFS and OS in advanced HCC in 2 rPhase 3 trials. PD-0332991 is an orally available, pyridopyrimidine-derived, selective inhibitor of CDK4/6, that results in the inhibition of RB protein phosphorylation &amp; cell cycle arrest. In preclinical studies, PD-0332991 has cytostatic activity, dependent on RB protein Methods: This is an open-label non-randomized single-institution study for subjects with inoperable, recurrent/refractory advanced HCC. Subjects must have failed or be intolerant of standard first-line therapy, sorafinib. Subjects receive 125 mg PD-0332991 po/d 1-21 of 28-day cycle until disease or clinical progression, unacceptable toxicity, withdrawal of consent or death. Tumor response by CT or MRI using mRECIST v1.1 is q8 w. Subjects are assessed for toxicity per NCI CTCAE, v4.0. Results: 10 pts (8m,2f) have been enrolled. Median age is 61.7 (r32-74) yr. PD-0332991 is well tolerated. The most common toxicities were neutropenia and thrombocytopenia with 3 G3 neutropenia requiring therapy delay. Non-serious AEs were ascites, pain, nausea, vomiting, diarrhea, lightheadedness, anorexia, neuropathy. LFT abnormalities were consistent with underlying ESLD. 3 pts expired due to liver failure before disease progression was observed by RECIST, at 70, 85 and 136 d. 3 subjects developed PD at 3, 5 and 8 m. 2 have received additional therapy. 4 subjects are on therapy, with best PFS being 8 m. Conclusions: PD-0332991 is well tolerated in subjects with HCC and cirrhosis. Primary toxicity is neutropenia and thrombocytopenia consistent with known safety profile of PD-0332991. No unexpected toxicities have been observed. Preliminary responses are encouraging. TTP compares favorably to other drug regimens. Clinical trial information: NCT01356628.