Journal of Clinical Oncology (J CLIN ONCOL)

Publications in this journal

• Article: comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of trial ACCORD 12/0405 Prodige2

  gerard jp, azria d, gourgou-bourgade s
  Journal of Clinical Oncology 02/2013;
• Article: Retroperitoneal sarcomas: 20 years experience at a tertiary Asian center

  SY Lee, M Teo, RHH Quek, BKP Goh, W Chen, AYF Chung, HN Koong, WK Wong, LL Ooi and KC Soo
  Journal of Clinical Oncology 02/2013; 29(e20522).
• Article: Reply to PP Singh, et al.

  Tsan YT, Lee CH, Wang JD, Chen PC
  Journal of Clinical Oncology 07/2012; 30:2570-2571.
• Article: Prevalence of autoimmune conditions in patients with marginal zone lymphoma: Exploratory analysis of a series of consecutive patients.

  Joanna Grabska, Bruno Bockorny, Ion Codreanu, Prerna Mewawalla, Constantin Dasanu, Joel Silver
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  ABSTRACT: Background: Recent literature suggests that an association exists between marginal zone lymphoma (MZL) and certain autoimmune conditions. Furthermore, MZL and autoimmune diseases may share same pathogenesis in these patients. The present study was set to identify the prevalence of autoimmune phenomena in MZL patients and compare it with same in general population. Methods: We conducted both retrospective and prospective analyses in a series of consecutive patients (n=24) with MZL that had been followed in outpatient setting. Median age was 71.8 years (range, 50-96). Records were reviewed for the presence of autoimmune abnormalities; length of the prospective analysis segment was ~24 months. Prevalence of autoimmune disorders in our cohort was compared to their respective prevalence in general population. Statistical analysis: The obtained values were tested for statistical significance using Fisher’s exact test for small number of observations (95% confidence); a p-value < 0.05 was considered significant. Results: A total of 50% patients included in our study had documented autoimmune conditions. Identified autoimmune disorders included Hashimoto thyroiditis (n=5), immune thrombocytopenia [ITP] (n=4), rheumatoid arthritis [RA] (n=1), Raynaud's phenomena (n=1), psoriasis (n=1), and autoimmune hemolytic anemia [AIHA] (n=1). Statistical analysis showed the following significance: Hashimoto thyroiditis (p=0.037), ITP (p<0.01), AIHA (p<0.01), RA(p=0.351), psoriasis (p=0.479), and Raynaud's phenomena (p=0.666). Conclusions: Circa half of MZL patients also have autoimmune conditions, thus significantly exceeding the overall prevalence in general population. Statistically significant differences in our MZL patients were recorded for Hashimoto thyroiditis, ITP, and AIHA. When compared to the prevalence in general population, the difference did not reach statistical significance for RA, psoriasis, and Raynaud's phenomena. However, this may be related to the relatively small size of the analyzed cohort. Therefore, larger studies would be useful before definitive conclusions can be drawn.
  Journal of Clinical Oncology 06/2012; 30(suppl):abstr e18543.
• Article: Prevalence of autoimmune manifestations in patients with large granular lymphocytic leukemia – exploratory analysis of a series of consecutive patients

  Bruno Bockorny, Joanna Grabska, Ion Codreanu, Prerna Mewawalla, Joel Silver, Constantin A. Dasanu
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  ABSTRACT: Prevalence of autoimmune manifestations in patients with large granular lymphocytic leukemia – exploratory analysis of a series of consecutive patients. Bruno Bockorny, Joanna Grabska, Ion Codreanu, Prerna Mewawalla, Joel Silver, Constantin Dasanu; University of Connecticut , Farmington , CT; The University of Arizona Medical Center, Tucson, AZ; University Of Connecticut, Farmington, CT; Gothic Park, hartdord, CT; St Francis Hospital , Hartford, CT Abstract Text: Background: Review of literature suggests certain autoimmune abnormalities to accompany LGL leukemia. The present study was set to identify the prevalence of autoimmune phenomena in LGL leukemia patients and compare it with same in general population. Methods: We conducted both retrospective and prospective analyses in a series of consecutive patients (n=11) with LGL leukemia that had been followed in outpatient setting. Median age was 71 years ( ± 14 years). The presence of associated autoimmune disorders in our cohort was compared to the published prevalence of these conditions in general population. Statistical analysis: The obtained values were tested for statistical significance using Fisher’s exact test for small number of observations (95% confidence); a p-value < 0.05 was considered significant. Results: A total of 45% patients in our study were diagnosed with autoimmune conditions (Table 1). Identified autoimmune disorders included rheumatoid arthritis [RA] (n=3), Hashimoto thyroiditis (n=3), Felty syndrome (n=1), anaplastic anemia (n=1), pernicious anemia (n=1), and leukocytoclastic vasculitis (n=1). Statistical analysis showed the following significance: Hashimoto thyroiditis (p=0.044), RA (p=0.003), Felty syndrome (p<0.001), anaplastic anemia (p<0.001), pernicious anemia (p<0.001), and leukocytoclastic vasculitis (p<0.001). Statistical difference was also noted for autoimmune serologic abnormalities, with ANA positivity present in 63.6% of the cases (p< 0.001) and RF present in 50% of the patients (p=0.005). Conclusions: Nearly half of LGL leukemia patients in our cohort had autoimmune disorders, thus significantly exceeding the overall prevalence in general population. Statistically significant differences were recorded for RA, Hashimoto thyroiditis, Felty syndrome, anaplastic anemia, pernicious anemia, leukocytoclastic vasculitis, ANA and RF positive serologies. The prevalence of Hashimoto thyroiditis and ANA positivity in our patient cohort was significantly higher than the one in existing literature. Given the relatively small size of the analyzed cohort, larger studies are expected to confirm our findings. Title: Prevalence of autoimmune manifestations in patients with large granular lymphocytic leukemia – exploratory analysis of a series of consecutive patients.
  Journal of Clinical Oncology 06/2012;
• Article: Distant metastasis in head and neck cancer: Baseline factors.

  Rahul Krishnatry, Tejpal Gupta, Vedang Murthy, Sudhir Vasudevan Nair, Deepa Nair, Pankaj Chaturvedi, A. K. Dcruz, Kumar Prabhash, Sarbani Laskar Ghosh, Ashwini Narsingrao Budrukkar, Jaiprakash Agarwal
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  ABSTRACT: Background: Loco-regional relapse is predominant pattern of failure in locally advanced head & neck squamous cell cancer (HNSCC). Distant metastasis (DM) is increasingly detected on follow-up. this study attempts to identify baseline patient, tumor & treatment characteristics which determine poor survival in radically treated HNSCC patients developing DM. Methods: Clinical outcome audit of HNSCC receiving radical treatment from 1990-2010 in a single HNCC radiotherapy (RT) clinic who developed DM, using electronic search of a prospectively maintained database. The Disease free survival (DFS) & overall survival (OS) were calculated using Kaplan Meier method. The Log rank test & Cox regression (p< 0.05 significant) were used for univariate & multivariate analysis respectively. Results: 104 HNC patients developed DM, baseline characteristics are shown in table 1. DM was detected at a median of 7(IQR 3-14) months from treatment completion & median survival after diagnosis of DM was 2.6 (0-6) months. The median DFS & OS were 19(13-26), 21.5(16-29) months respectively. On univariate analysis, factors affecting DFS & OS were advanced tumor and nodal stage, perinodal extension & treatment factors (surgery & RT gap >30 days). On multivariate analysis stage and PNE remained significant for DFS while only stage showed significance for OS. Conclusions: Locally advanced stage of presentation (stage IV, T4, N2+) is the most important baseline factor determining poor outcome in HNC patients developing DM. Trials for aggressive primary systemic treatment (chemotherapy, targeted agents) are needed.
  Journal of Clinical Oncology 05/2012; 30(15_suppl):e16021.
• Article: The prognostic role of serum albumin in patients receiving induction chemotherapy for acute myeloid leukemia (AML).

  Hossein Sadrzadeh, Andrew Mark Brunner, Benjamin Jacob Drapkin, Loren Babirak, Lillian Werner, Karen K. Ballen, Philip C. Amrein, Eyal C. Attar, Yi-Bin Albert Chen, Thomas R. Spitzer, Steven L McAfee, Donna S. Neuberg, Amir Tahmasb Fathi
  Journal of Clinical Oncology 05/2012; J Clin Oncol 30, 2012 (suppl; abstr 6618)(30).
• Article: A seasonal pattern of presentation in younger patients with de novo acute myeloid leukemia (AML)

  Benjamin Jacob Drapkin, Hossein Sadrzadeh, Andrew Mark Brunner, Lillian Werner, Loren Babirak, Eyal C. Attar, Karen K. Ballen, Steven L McAfee, Philip C. Amrein, Yi-Bin Albert Chen, Richard M. Stone, Amir Tahmasb Fathi
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  ABSTRACT: Abstract: Background: Seasonal variation in AML has been studied in a wide variety of populations and locations, with primarily negative results. These investigations may have been undermined by the heterogeneity of the disease, as de novo and secondary AML can vary in disease presentation and trajectory, likely reflecting distinct pathogenesis.We investigated seasonal variation in the incidence of AML diagnosed at Massachusetts General Hospital (MGH) from 1992 through 2011, focusing on de novo disease among younger patients. Methods: We assembled a database of 511 biopsy-proven cases of adult-onset AML (age > 18 years), from the MGH electronic medical record, using a systematic search algorithm with IRB approval. We subdivided this database into three cohorts: (1) de novo AML diagnosed prior to age 50 (2) de novo AML diagnosed after age 50, and (3) secondary AML, preceded by chemotherapy, myelodysplasia or myeloproliferative disease. Diagnosis dates were grouped into quarters (Jan-Mar, Apr-Jun, Jul-Sep, Oct-Dec). Divergence of quarterly incidence from a null hypothesis of uniformity was evaluated by chi square analysis. Results: Among patients under 50-years-old with de novo AML, we found a 44% increase in incidence between October and December (Table, p=0.04). There was no significant variation throughout the rest of the calendar year. Furthermore, the incidence of both de novo AML diagnosed after age 50 and secondary AML conformed to a uniform quarterly distribution. As expected, the majority of AML patients under age 50 demonstrated intermediate-risk cytogenetics, most frequently normal karyotype. Conclusions: We found a significantly increased incidence of de novo AML in younger patients between the months of October and December, diagnosed at MGH from 1992 through 2011. This may reflect a local environmental or infectious exposure that is not relevant to the pathogenesis of AML in older patients or those in whom AML develops due to prior therapy or previous hematological disorder. Investigation of this exposure is ongoing. Quarter All cases Under 50 y/o Over 50 y/o Secondary Jan-Mar 23% 17% 26% 23% Apr-Jun 25% 23% 25% 27% Jul-Sep 25% 24% 24% 26% Oct-Dec 27% 36% 26% 24% Total patients 511 108 182 221 p value 0.51 0.04 0.97 0.77
  Journal of Clinical Oncology 05/2012; J Clin Oncol 30, 2012 (suppl; abstr 6617)(30).
• Article: Prospective evaluation of serial 2-hydroxyglutarate in acute myeloid leukemia (AML) to determine response to therapy and predict relapse

  Amir Tahmasb Fathi, Omar Ibrahim Abdel-Wahab, Hossein Sadrzadeh, Julia Foster, Meghan Burke, Darrell R. Borger, A. John Iafrate, Sophia Adamia, Suiyang Liu, Karen K. Ballen, Philip C. Amrein, Eyal C. Attar, Kimberly Straley, Katharine Yen, David P. Schenkein, Donna S. Neuberg, Ross L. Levine, Yi-Bin Albert Chen, Richard M. Stone
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  ABSTRACT: Background: Mutations in isocitrate dehydrogenase (IDH1 and IDH2) occur in 10-20% of AML patients and result in production of 2-hydroxyglutarate (2-HG). We hypothesize that serial 2-HG quantification may be used to monitor response and predict relapse in patients with AML. Methods: We are conducting a prospective study at MGH and DFCI to (1) assess changes in serum and urine 2-HG levels during treatment in patients with newly diagnosed AML, (2) compare 2-HG levels in serum, urine, and bone marrow and, (3) serially compare 2-HG levels with IDH1/2mutant allele burden. In those with elevated serum 2-HG (≥1000ng/ml), 2-HG is monitored serially or at relapse. Results: To date, 20 patients have been enrolled, 5 (25%) of whom had elevated baseline serum 2-HG. All 5 were found to have IDH1/2 mutations. The serum 2-HG for these patients was significantly higher than for those who were IDH-wt (median 1933 vs 87ng/mL; p<0.001). Urine 2-HG was also higher in IDH-mutant patients (median 30500 vs 4230ng/mL; p<0.021), as was bone marrow 2-HG (median 9870 vs 309ng/mL; p<0.005). Serum 2-HG levels strongly correlated with that in urine (R2 0.987). Serum 2-HG decreased in all IDH mutant patients on therapy, but more rapidly in those receiving induction chemotherapy (Table), all of whom achieved remission, than those receiving hypomethylatingagents. Conclusions: Patients with IDH-mutant AML have markedly elevated serum and urine 2-HG. 2-HG levels decreased with therapy and there is a strong correlation between serum and urine 2-HG. Data on the sensitivity of serial 2-HG monitoring as well as comparison with mutant IDH1/2allele burden will be presented. This data suggests that serial 2-HG quantification may be a valuable non-invasive biomarker in this genetically defined subset of AML. Serial analysis of serum 2HG (ng/mL) during therapy in IDH-mutant AML. Day 0 Day 7 Day 14 Day 30 Day 60 Day 110 Patient 1 (5-azacitidine) (IDH2 R140Q) 1,933 2,125 2,006 1,599 2,077 60 Patient 2 (induction) (IDH1 R132H) 2,070 1,019 295 363 195 Patient 3 (induction) (IDH1 R132H) 66,207 1,477 1,043 407 154 Patient 4 (induction) (IDH2 R140Q) 1,054 249 60 84 106 Patient 5 (5-azacitidine) (IDH2 R140Q) 1,296 786 935 503
  Journal of Clinical Oncology 05/2012; J Clin Oncol 30, 2012 (suppl; abstr 6606)(30).
• Article: History of autoimmunity to predict clinical response to DNA methyltransferase inhibitors (DNMTI) in myelodysplastic syndromes (MDS), and MDS-derived acute myeloid leukemias (AML).

  Ashkan Emadi, Hossein Sadrzadeh, Payal Patal, Kathleen H. Burns, Amy Duffield, Karen K. Ballen, Philip C. Amrein, Eyal C. Attar, B. Douglas Smith, Amir Tahmasb Fathi
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  ABSTRACT: Background: MDS is comprised of a heterogeneous group of clonal myeloid disorders. Chronic immune stimulation has been reported as a trigger for the development of a subset of MDS, with increased autoreactive cytotoxic T cells present in the bone marrow. Autoimmunity has been associated with MDS and other marrow failures. DNMTIs, 5-azacytidine and decitabine, are approved for the treatment of MDS. In addition to epigenetic impacts, these agents may have immunomodulatory effects, including augmentation of MAGE-related anti-tumor response. These reports and clinical observations led us to hypothesize that MDS patients with a history of autoimmunity may be more responsive to DNMTIs. Methods: To identify patients with MDS, a retrospective database review (2007-2011) was performed at Johns Hopkins Hospital (JHH) and Massachusetts General Hospital (MGH). The MGH data also included those with AML whose disease had progressed from MDS. Past medical history of autoimmune disorders, diagnosis, blood counts, flow cytometry and cytogenetics were reviewed. Patients with aplastic anemia, paroxysmal nocturnal hemoglobinuria or non-malignant etiologies of cytopenia were excluded. Patients with MDS were further studied if they were treated with DNMTI. Results: Of 137 patients with MDS or MDS/AML, 23 had a documented history of autoimmunity in the medical record. Of these, 15 (65.2%) experienced a response to therapy as defined by the International Working Group. Of 114 patients without a documented history of autoimmunity, 34 (29.8%) achieved a response during therapy, a significantly lower percentage as compared to those with autoimmune conditions (p-value 0.002, t-test). The majority of responding patients with a history of autoimmunity displayed a normal karyotype (9 of 15 patients). Conclusions: A history or co-presence of an autoimmune disorder may predict a high likelihood of achieving a clinical response to DNMTIs. Correlative studies in this unique population of patients with MDS and MDS/AML and prospective clinical studies are needed to improve our understanding of the possible mechanism of action of DNMTIs in these patients.
  Journal of Clinical Oncology 05/2012; J Clin Oncol 30, 2012 (suppl; abstr 6629)(30).
• Article: Accrual of under-represented minority women to breast cancer clinical trials in Inland Empire, California.

  Yuan Yuan, Padma Tadi Uppala, Sharon S. Lum, John W. Morgan, Carlos Garberoglio
  Journal of Clinical Oncology 01/2012; 30(27).
• Article: Multiple Cytokine-Producing Plasmablastic Solitary Plasmacytoma of Bone With Polyneuropathy, Organomegaly, Endocrinology, Monoclonal Protein, and Skin Changes Syndrome.

  Nakayama-Ichiyama S, Yokote T, Hirata Y, Iwaki K, Akioka T, Miyoshi T, Nishiwaki U, Masuda Y, Hiraoka N, Takayama A, Tsuji M, Hanafusa T
  Journal of Clinical Oncology 01/2012;
• Article: Chronic Lymphocytic Leukemia After Chronic Myeloid Leukemia In The Same Patient: Two Different Genomic Events And A Common Treatment?

  D'Arena G, Gemei M, Luciano L, D'Auria F, Deaglio S, Statuto T, Bianchino G, Grieco V, Mansueto G, Guariglia R, Pietrantuono G, Martorelli MC, Villani O, Del Vecchio L, Musto P
  Journal of Clinical Oncology 01/2012;
• Article: Monitoring of minimal residual disease in NPM1-mutated acute myeloid leukemia: a study from the German-Austrian acute myeloid leukemia study group.

  Krönke J, Schlenk RF, Jensen KO, Tschürtz F, Corbacioglu A, Gaidzik VI, Paschka P, Onken S, Eiwen K, Habdank M, [......], von Lilienfeld-Toal M, Germing U, Haase D, Mergenthaler HG, Krauter J, Ganser A, Göhring G, Schlegelberger B, Döhner H, Döhner K
  Journal of Clinical Oncology 07/2011; 29(19):2709-16.
• Article: Gollins S, Sun Myint A, Haylock B et al. Preoperative Chemoradiotherapy Using Concurrent Capecitabine and Irinotecan in MRI defined Locally Advanced Rectal Cancer: Impact on Long Term Clinical Outcomes. J Clin Oncol 2011;29:1042-1049.

  Gollins S, Sun Myint A, Haylock B et al
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  ABSTRACT: Purpose To assess long-term clinical outcomes of preoperative chemoradiotherapy of magnetic resonance imaging (MRI)–defined locally advanced rectal adenocarcinoma using concurrent irinotecan and capecitabine. Patients and Methods One hundred ten patients without distant metastases entered this phase II trial North West/North Wales Clinical Oncology Group (NWCOG) -2 after MRI demonstration of tumor threatening (� 2 mm) or involving mesorectal fascia. Pelvic radiotherapy was given to 45 Gy in 25 fractions over 5 weeks with concurrent oral capecitabine at 650 mg/m2 twice per day continuously days 1 through 35 and intravenous irinotecan at 60 mg/m2 once weekly weeks 1 to 4. One hundred seven patients subsequently underwent surgical resection. Results Comparing prechemoradiotherapy MRI scans with histology of the resected specimen, 72 patients (67%) had their initial MRI T stage downstaged and 64 patients (80%) had their N stage downstaged. Twenty-four patients (22%) demonstrated a pathologic complete response (ypCR) and 98 patients (92%) demonstrated a negative circumferential resection margin (� 1 mm). Three-year local recurrence-free survival was 96.9%, metastasis-free survival (MFS) was 71.1%, disease-free survival was (DFS) 63.5%, and overall survival (OS) was 88.2%. By univariate analysis, lower histologic stage was significantly associated with superior MFS, DFS, and OS, whether expressed as ypT0-2 versus ypT3-4, ypN0 versus ypN1-2, or ypCR/microfoci (near-ypCR) versus other patients. By multivariate analysis both ypN stage (P � .048) and ypCR/microfoci/ others (P � .013) remained significant predictors of DFS but only ypCR/microfoci/others for OS (P � .005) with no difference in outcome between ypCR compared to microfoci. Conclusion This regimen demonstrates high response rates and promising long-term survival. Downstaging to ypCR/microfoci may be a useful short-term surrogate for long-term survival but needs validation in large phase III trials powered for survival outcomes.
  Journal of Clinical Oncology 01/2011;
• Article: Accrual of underrepresented minority women to breast cancer clinical trials in the Inland Empire, California.

  Y. Yuan, P. Uppala, S. S. Lum, C. Garberoglio, H. R. Mirshahidi, R. Cassady, J. Morgan, C. Chen
  Journal of Clinical Oncology 01/2011; 29.
• Article: Trastuzumab-resistant HER2-positive metastatic breast cancer: Comparing results of lapatinib and capecitabine in brain and other metastatic sites.

  Eduardo Jorge Cortes, Margarita Bomfim, Bruno Freitas Vargas, Frederico Muller, Bruno Bockorny da Silva
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  ABSTRACT: Background: Trastuzumab, anthracycline, and taxane resistant HER2-positive metastatic breast cancer has poor prognosis. Progression in brain metastasis (BM) commonly leads to difficult diagnostic interpretation and treatment decisions, poor quality of life, and death. Methods: Consented patients (pts) with HER2-positive metastatic breast cancer, ECOG ≤2, with resistance to trastuzumab, taxane, and anthracyclines, were recruited for treatment with daily lapatinib (L) (1,250 mg daily) and capecitabine (C) (2,000 mg/m2/day days 1-14) in a 21 day cycle. Progression was evaluated by RECIST and statistics by SPSS. Results: We enrolled 10 pts (median age 44), median follow up was 19.51 months (M). One patient had grade 3 toxicity due to C and was kept with L only; no other patient discontinued L nor C due to toxicity. Nine (90%) pts had ≥2 metastatic sites, one pt had BM only, and 6 pts had BM in addition to other sites. Median time to progression (TTP) was 9.10 M for the 10 pts, 13.86 M for BM as site of first progression, and 5.90 M for non-BM progression (p<0.05). BM was the most common site for first progression, seen in 4 pts. There was no new BM lesion during treatment. Overall BM response to Tx was 50% (1 complete response, 2 partial responses). In all 4 patients that progressed in central nervous system, head NMR showed enlarged metastatic lesions with central liquefied images, and were interpreted initially as radio/chemo necrosis. Two pts had neurological symptoms and discontinued L and C. The last two pts that progressed in brain had their metastatic images interpreted as necrosis also. However, specific NMR vascular analysis revealed higher perfusion/permeability image patterns, interpreted as caused by tumor activity. They went to BM surgical resection and histology showed tumor cells and 40% of necrosis. Both patients are well and without signs or symptoms after surgery. Conclusions: Brain was the most common metastatic site in this pts, and BM had a longer TTP than the other metastasis. Surgical removal of BM appears to help patients and should be considered in earlier stage of enlargement of lesions. NMR perfusion-permeability studies may facilitate medical decisions.
  Journal of Clinical Oncology 06/2010;