Khaldoun Almhanna

Moffitt Cancer Center, Tampa, FL, USA

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Publications (11)20.09 Total impact

  • Article: Lymph Node Harvest in Esophageal Cancer After Neoadjuvant Chemoradiotherapy.
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    ABSTRACT: BACKGROUND: This study was designed to determine the effects of lymph node (LN) harvest on survival in esophageal cancer after neoadjuvant chemoradiation (nCRT). METHODS: An analysis of surgically resected esophageal cancer patients after nCRT was performed to determine an association between the number of LNs resected and survival. Overall survival (OS) and disease-free survival (DFS) curves were calculated according to the Kaplan-Meier method and log-rank analysis. Multivariate analysis (MVA) was performed by the Cox proportional hazard model. RESULTS: We identified 358 patients with a mean follow-up of 27.3 months. The number of LN removed was not impacted by the type of surgical procedure. The number of LNs removed (<10 vs. ≥10, <12 vs. ≥12, and <15 vs. ≥15) did not impact OS or DFS. We found a significant difference in OS and DFS by pathologic response. The median and 5-year OS for patients with complete, partial, and no response was 65.6 months and 52.7 %, 29.7 months and 30.4 %, and 17.7 months and 25.4 % (p = 0.0002). However, the number of LN harvested did not impact OS and DFS when patients were stratified by pathologic response. MVA also revealed that the number of lymph nodes removed was not prognostic for OS or DFS. Higher age, higher stage, and less than a complete response were associated with a decreased OS. Higher stage and less than a complete response were prognostic for worse DFS. CONCLUSIONS: The number of LNs harvested during esophagectomy does not impact survival after nCRT. Stage and pathologic response continue to be the strongest prognostic factors for survival in esophageal cancer after nCRT.
    Annals of Surgical Oncology 04/2013; · 4.17 Impact Factor
  • Article: The impact of body mass index on esophageal cancer.
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    ABSTRACT: Surgeons are increasingly operating on patients who are overweight or obese. The influence of obesity on surgical and oncologic outcomes has only recently been addressed. We focus this review on obesity and its impact on esophageal cancer. Recent literature and our own institutional experience were reviewed to determine the impact of body mass index on the perioperative and long-term outcomes of patients with esophageal cancer. With few exceptions, no significant differences were seen in perioperative outcomes or survival in patients treated for esophageal cancer when stratified by body mass index. Although obesity poses increased operative challenges to the surgeon, surgical.
    Cancer control: journal of the Moffitt Cancer Center 04/2013; 20(2):138-43.
  • Article: Endoscopic Therapy of Neoplasia Related to Barrett's Esophagus and Endoscopic Palliation of Esophageal Cancer.
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    ABSTRACT: Barrett's esophagus (BE) is the most important identifiable risk factor for the progression to esophageal adenocarcinoma. This article reviews the current endoscopic therapies for BE with high-grade dysplasia and intramucosal cancer and briefly discusses the endoscopic palliation of advanced esophageal cancer. The diagnosis of low-grade or high-grade dysplasia (HGD) is based on several cytologic criteria that suggest neoplastic transformation of the columnar epithelium. HGD and carcinoma in situ are regarded as equivalent. The presence of dysplasia, particularly HGD, is also a risk factor for synchronous and metachronous adenocarcinoma. Dysplasia is a marker of adenocarcinoma and also has been shown to be the preinvasive lesion. Esophagectomy has been the conventional treatment for T1 esophageal cancer and, although debated, is an appropriate option in some patients with HGD due to the presence of occult cancer in over one-third of patients. Endoscopic ablative modalities (eg, photodynamic therapy and cryoablation) and endoscopic resection techniques (eg, endoscopic mucosal resection) have demonstrated promising results. The significant morbidity and mortality of esophagectomy makes endoscopic treatment an attractive potential option.
    Cancer control: journal of the Moffitt Cancer Center 04/2013; 20(2):117-29.
  • Article: Neoadjuvant or adjuvant therapy for resectable esophageal cancer: is there a standard of care?
    Khaldoun Almhanna, Ravi Shridhar, Kenneth L Meredith
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    ABSTRACT: Carcinoma of the esophagus is an aggressive and lethal disease with an increasing incidence worldwide. Despite changes in the treatment approach over the past two decades and even following complete resection, most patients will eventually relapse and die as a result of their disease. Several clinical trials evaluated different modalities in treating locally advanced esophageal cancer; however, because of stage migration and the changes in disease epidemiology, applying these trials to clinical practice has become a daunting task. We searched Medline and conference abstracts for randomized studies published in the past three decades. We restricted our search to articles published in English. Neoadjuvant chemoradiotherapy followed by surgical resection is an accepted standard of care in the United States for patients with locally advanced esophageal cancer. Esophagectomy remains an essential component of treatment and can lead to improved overall survival, especially when performed at high-volume institutions. The role of adjuvant chemotherapy following curative resection in patients who underwent neoadjuvant chemotherapy and radiation remains unclear. Several questions still need to be answered regarding the use of neoadjuvant or adjuvant therapy for patients with resectable esophageal cancer. The optimal chemotherapy regimen has not yet been identified for these patients, although newer therapies show promise.
    Cancer control: journal of the Moffitt Cancer Center 04/2013; 20(2):89-96.
  • Article: Radiation therapy and esophageal cancer.
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    ABSTRACT: Squamous cell carcinoma and adenocarcinoma account for more than 90% of all esophageal cancer cases. Although the incidence of squamous cell carcinoma has declined, the incidence of adenocarcinoma has risen due to increases in obesity and gastroesophageal reflux disease. The authors examine the role of radiation therapy alone (external beam and brachytherapy) for the management of esophageal cancer or combined with other modalities. The impact on staging and appropriate stratification of patients referred for curative vs palliative intent with modalities is reviewed. The authors also explore the role of emerging radiation technologies. Current data show that neoadjuvant chemoradiotherapy followed by surgical resection is the accepted standard of care, with 3-year overall survival rates ranging from 30% to 60%. The benefit of adjuvant radiation therapy is limited to patients with node-positive cancer. The survival benefit of surgical resection after chemoradiotherapy remains controversial. External beam radiation therapy alone results in few long-term survivors and is considered palliative at best. Radiation dose-escalation has failed to improve local control or survival. Brachytherapy can provide better long-term palliation of dysphagia than metal stent placement. Although three-dimensional conformal treatment planning is the accepted standard, the roles of IMRT and proton therapy are evolving and potentially reduce adverse events due to better sparing of normal tissue. Future directions will evaluate the benefit of induction chemotherapy followed by chemoradiotherapy, the role of surgery in locally advanced disease, and the identification of responders prior to treatment based on microarray analysis.
    Cancer control: journal of the Moffitt Cancer Center 04/2013; 20(2):97-110.
  • Article: Targeting the human epidermal growth factor receptor 2 in esophageal cancer.
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    ABSTRACT: The importance of human epidermal growth factor-2 (HER2) in terms of prognosis and aggressiveness of growth has long been known in breast cancer, and interruption of its growth cascade by agents such as trastuzumab and lapatinib has markedly improved outcomes for these patients with HER2 overexpression. HER2 overexpression also occurs in many other tumor types, including esophageal cancer. In this disease, a different scoring system for determining overexpression is used. Limited data exist concerning the biological and therapeutic implications of HER2 overexpression in esophageal cancer. One trial, the so-called ToGA trial, included patients with advanced gastric and gastroesophageal junction (GEJ) tumors that overexpressed HER2. Patients who received trastuzumab plus cisplatin-based chemotherapy had more responses and longer progression-free and overall survival than those who received the chemotherapy alone. Enthusiasm concerning these results must be tempered by the facts that only 25% of the study group had GEJ tumors and, of these, only 33% had HER2 overexpression. Thus, the role of trastuzumab in the management of HER2-overexpressing esophageal cancers remains to be determined. In addition to presenting data on the HER2 cascade, the authors review clinical trials performed to date and also present the validated standard scoring system for HER2 overexpression in esophageal cancer.
    Cancer control: journal of the Moffitt Cancer Center 04/2013; 20(2):111-6.
  • Article: Outcomes Associated with Surgery for T4 Esophageal Cancer.
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    ABSTRACT: BACKGROUND: T4 esophageal cancer often portends a dismal prognosis even after surgical resection. Historical incomplete resections and poor survival rates often make surgery palliative rather than curative. METHODS: Using a comprehensive esophageal cancer database, we identified patients who underwent an esophagectomy for T4 tumors between 1994 and 2011. Neoadjuvant treatment (NT) and pathologic response variables were recorded, and response was denoted as complete response (pCR), partial response (pPR), and nonresponse (NR). Clinical and pathologic data were compared. Survival was calculated using Kaplan-Meier curves with log-rank tests for significance. RESULTS: We identified 45 patients with T4 tumors all who underwent NT. The median age was 60 years (range, 31-79 years) with a median follow-up of 27 months (range, 0-122 months). There were 19 pCR (42 %), 22 pPR (49 %), and 4 NR (9 %). R0 resections were accomplished in 43 (96 %). There were 18 recurrences (40 %) with a median time to recurrence of 13.5 months (2.2-71 months). In this group pCR represented 7 (38.9 %), whereas pPR and NR represented 10 (55.5 %), and 1 (5.5 %) respectively. The overall and disease-free survival for all patients with T4 tumors were 35 and 36 %, respectively. Patients achieving a pCR had a 5 year overall and disease-free survival of 53 and 54 %, compared with pPR 23 and 28 %, while there were no 5 year survivors in the NR cohort. CONCLUSION: We have demonstrated that neoadjuvant therapy and downstaging of T4 tumors leads to increased R0 resections and improvements in overall and disease-free survival.
    Annals of Surgical Oncology 03/2013; · 4.17 Impact Factor
  • Article: Increased survival associated with surgery and radiation therapy in metastatic gastric cancer: A Surveillance, Epidemiology, and End Results database analysis.
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    ABSTRACT: BACKGROUND: Patients with metastatic gastric cancer have poor survival. The purpose of this study was to compare outcomes of metastatic gastric cancer patients stratified by surgery and radiation therapy. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was accessed to identify patients with AJCC M1 stage IV gastric cancer (based on the American Joint Committee on Cancer Cancer Staging Manual, 6th edition) between 2004 thru 2008. Patients were divided into 4 groups: group 1, no surgery or radiation; group 2, radiation alone; group 3, surgery alone; group 4, surgery and radiation. Survival analysis was determined by Kaplan-Meier and log-rank analysis. Multivariate analysis (MVA) was analyzed by the Cox proportional hazard ratio model. RESULTS: A total of 5072 patients were identified. Surgery and/or radiation were associated with a survival benefit. Median and 2-year survival for groups 1, 2, 3, and 4 was 7 months and 8.2%, 8 months and 8.9%, 10 months and 18.2%, and 16 months and 31.7%, respectively (P < .00001). MVA for all patients revealed that surgery and radiation were associated with decreased mortality whereas T-stage, N-stage, age, signet ring histology, and peritoneal metastases were associated with increased mortality. In patients treated with surgery, MVA showed that radiation was associated with decreased mortality, whereas T-stage, N-stage, age, removal of < 15 lymph nodes, signet ring histology, and peritoneal metastases was associated with increased mortality. Age was the only prognostic factor in patients who did not undergo surgery. CONCLUSIONS: Surgery and radiation are associated with increased survival in a subset of patients with metastatic gastric cancer. Prospective trials will be needed to address the role and sequence of surgery and radiation in metastatic gastric cancer. Cancer 2013;. © 2013 American Cancer Society.
    Cancer 01/2013; · 4.77 Impact Factor
  • Article: Body mass index and perioperative complications after oesophagectomy for adenocarcinoma: a systematic database review.
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    ABSTRACT: Given the increasing rate of obesity, the effects of excessive body weight on surgical outcomes constitute a relevant quality of care concern. Our aim was to determine the relationship between preoperative body mass index (BMI) on perioperative complications after oesophagectomy for adenocarcinoma of the oesophagus. Retrospective database review. Single institution high volume oncological tertiary care referral centre. From our comprehensive oesophageal cancer database consisting of 709 patients, we stratified patients according to BMI: 155 normal-weight (BMI 20-24), 198 overweight (BMI 25-29) and 187 obese (BMI ≥30) patients. All patients underwent oesophagectomy for cancer. PRIMARY AND SECONDARY OUTCOME MEASURES: Incidences of preoperative risk factors and perioperative complications in each group were analysed. The patient cohort consisted of 474 men and 66 women with a mean age of 64.3 years (28-86). They were similar in terms of demographics and comorbidities, with the exception of a younger age (65.2 vs 65.4 vs 62.5 years, p=0.0094), and a higher incidence of diabetes (9.1% vs 13.2% vs 22.7%, p=0.001), hiatal hernia (16.8% vs 17.8% vs 28.8%, p=0.009) and Barrett oesophagus (24.7% vs 25.4% vs 36.2%, p=0.025) for obese patients. The type of surgery performed, overall blood loss, extent of lymphadenectomy, R0 resections and complications were not influenced by BMI on univariate and multivariate analysis. In our experience, patients with an elevated BMI and oesophageal adenocarcinoma do not experience an increase in morbidity and mortality after oesophagectomy as stated in previous reports, when performed at a high volume centre. Additionally, BMI did not affect the quality of oncological resection as determined by number of harvested lymph-nodes and rates of R0 resections. MCC 15030, IRB 105286.
    BMJ open. 01/2013; 3(5).
  • Article: Body mass index and survival in esophageal adenocarcinoma treated with chemoradiotherapy followed by esophagectomy.
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    ABSTRACT: Body mass index (BMI) has been linked with inferior outcomes in gastrointestinal malignancies. The purpose of this study is to evaluate the effect of BMI on survival in patients with esophageal adenocarcinoma. Medical records were analyzed for patients who underwent esophagectomy after neoadjuvant chemoradiotherapy (nCRT) for adenocarcinoma from 2000 to the present. Patients were grouped into BMI ≤ 25, >25-30, >30-35, and BMI >35. Overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method. Multivariate analysis (MVA) was performed using Cox proportional hazard regression model. We identified 303 patients for the analysis. The only difference in patient characteristics between groups was gender. We found no difference in OS and DFS associated with BMI (p=0.3297 for OS; p=0.5950 for DFS). There were no differences in postoperative complications or mortality between BMI groups. MVA revealed that higher stage and less than a complete response to nCRT were prognostic for worse OS and DFS, while age, gender, type of surgery, year of diagnosis, and BMI were not prognostic. BMI was neither associated with surgical complications nor survival in patients with esophageal adenocarcinoma treated with nCRT. BMI should not be considered a contraindication to surgical resection after nCRT.
    Journal of Gastrointestinal Surgery 03/2012; 16(7):1296-302. · 2.83 Impact Factor
  • Article: Pathologic nonresponders after neoadjuvant chemoradiation for esophageal cancer demonstrate no survival benefit compared with patients treated with primary esophagectomy.
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    ABSTRACT: Neoadjuvant chemoradiation (NCRT) has become the preferred treatment for patients with locally advanced esophageal cancer. Survival often is correlated to degree of pathologic response; however, outcomes in patients who are found to be pathologic nonresponders (pNR) remain uninvestigated. This study was designed to evaluate survival in pNR to NCRT compared with patients treated with primary esophagectomy (PE). Using our comprehensive esophageal cancer database, we identified patients treated with NCRT and deemed pNR along with patients who proceeded to PE. Clinical and pathologic data were compared using Fisher's exact and χ(2), whereas Kaplan-Meier estimates were used for survival analysis. We identified 63 patients treated with NCRT and were found to have a pNR, and 81 patients who underwent PE. Disease-free (DFS) and overall survival (OS) were significantly decreased in the pNR group compared with those treated with PE (10 vs. 50 months (0-152), P < 0.001 and 13 vs. 50 months (0-152), P < 0.001, respectively). For patients with stage II disease, DFS and OS were similarly decreased in pathologic nonresponders (13 vs. 62 months (0-120), P < 0.001 and 31 vs. 62 months (0-120), P = 0.024, respectively). There were no differences in DFS or OS for patients with stage III disease (10 vs. 14 months (0-152), P = 0.29 and 10 vs. 19 months (0-152), P = 0.16, respectively). Pathologic nonresponders to NCRT for esophageal cancer receive no benefit in DFS or OS compared with patients treated with PE. For patients with stage II disease, DFS and OS are, in fact, significantly decreased in the pNR.
    Annals of Surgical Oncology 11/2011; 19(5):1678-84. · 4.17 Impact Factor