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ABSTRACT: Gastric cancer (GC) is a major health burden throughout the world, especially in certain endemic regions. GC is commonly diagnosed at an advanced stage because of the lack of early detection strategies and is usually associated with a dismal outcome. For patients with localized GC (LGC), surgery is the best cure: cure rates are highly associated with the surgical pathology stage. Adjunctive therapies improve the cure rates by about an additional 10%. Therefore, a multimodality approach is highly recommended for all patients with LGC. This article highlights some of the therapeutic advances made against GC and features important ongoing trials.
Gastroenterology clinics of North America 06/2013; 42(2):359-69. · 2.56 Impact Factor
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Shumei Song,
Dipen M Maru, Jaffer A Ajani,
Chia-Hsin Chan,
Soichiro Honjo,
Hui-Kuan Lin,
Arlene Correa,
Wayne L Hofstetter,
Marta Davila,
John Stroehlein,
Lopa Mishra
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ABSTRACT: TGF-β and Notch signaling pathways play important roles in regulating self-renewal of stem cells and gastrointestinal carcinogenesis. Loss of TGF-β signaling components activates Notch signaling in esophageal adenocarcinoma, but the basis for this effect has been unclear. Here we report that loss of TGF-β adapter β2SP (SPNB2) activates Notch signaling and its target SOX9 in primary fibroblasts or esophageal adenocarcinoma cells. Expression of the stem cell marker SOX9 was markedly higher in esophageal adenocarcinoma tumor tissues than normal tissues, and its higher nuclear staining in tumors correlated with poorer survival and lymph node invasion in esophageal adenocarcinoma patients. Downregulation of β2SP by lentivirus short hairpin RNA increased SOX9 transcription and expression, enhancing nuclear localization for both active Notch1 (intracellular Notch1, ICN1) and SOX9. In contrast, reintroduction into esophageal adenocarcinoma cells of β2SP and a dominant-negative mutant of the Notch coactivator mastermind-like (dnMAN) decreased SOX9 promoter activity. Tumor sphere formation and invasive capacity in vitro and tumor growth in vivo were increased in β2SP-silenced esophageal adenocarcinoma cells. Conversely, SOX9 silencing rescued the phenotype of esophageal adenocarcinoma cells with loss of β2SP. Interaction between Smad3 and ICN1 via Smad3 MH1 domain was also observed, with loss of β2SP increasing the binding between these proteins, inducing expression of Notch targets SOX9 and C-MYC, and decreasing expression of TGF-β targets p21(CDKN1A), p27 (CDKN1B), and E-cadherin. Taken together, our findings suggest that loss of β2SP switches TGF-β signaling from tumor suppression to tumor promotion by engaging Notch signaling and activating SOX9. Cancer Res; 73(7); 1-11. ©2013 AACR.
Cancer Research 03/2013; · 7.86 Impact Factor
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ABSTRACT: Barrett's esophagus is the precursor lesion of esophageal adenocarcinoma, whose progression follows sequential stages. However, the low progression rate and the inadequacy and subjective interpretation of histologic grading in predicting Barrett's esophagus progression call for more objective biomarkers that can improve risk prediction. We conducted a genome-wide profiling of 754 human microRNAs (miRNA) in 35 normal epithelium, 34 Barrett's esophagus, and 36 esophageal adenocarcinoma tissues using TaqMan real-time PCR-based profiling. Unsupervised hierarchical clustering using 294 modestly to highly expressed miRNAs showed clear clustering of two groups: normal epithelium versus Barrett's esophagus/esophageal adenocarcinoma tissues. Moreover, there was an excellent clustering of Barrett's metaplasia (without dysplasia) tissues from normal epithelium tissues. However, Barrett's esophagus tissues of different stages and esophageal adenocarcinoma tissues were interspersed. There were differentially expressed miRNAs at different stages. The majority of miRNA aberrations involved upregulation of expression in Barrett's esophagus and esophageal adenocarcinoma tissues, with the most dramatic alterations occurring at the Barrett's metaplasia stage. Known oncomiRs, such as miR-21, miR-25, and miR-223, and tumor suppressor miRNAs, including miR-205, miR-203, let-7c, and miR-133a, showed progressively altered expression from Barrett's esophagus to esophageal adenocarcinoma. We also identified a number of novel miRNAs that showed progressively altered expression, including miR-301b, miR-618, and miR-23b. The significant miRNA alterations that were exclusive to esophageal adenocarcinoma but not Barrett's esophagus included miR-375 downregulation and upregulation of five members of the miR-17-92 and its homologue clusters, which may become promising biomarkers for esophageal adenocarcinoma development. Cancer Prev Res; 6(3); 196-205. ©2013 AACR.
Cancer Prevention Research 03/2013; 6(3):196-205. · 4.91 Impact Factor
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ABSTRACT: Gastric cancer confers a poor prognosis even when diagnosed as localized disease. Multimodality therapy improves the cure rate of patients with localized cancer. However, adjunctive therapeutic approaches differ in different regions of the world. This review focuses on the current standards and unresolved issues based on updated literature on therapy for localized gastric cancer. In the USA, the Intergroup 0116 trial established the use of postoperative chemoradiotherapy as a standard for patients who have surgery first for treatment of gastric cancer. In Europe, the MAGIC trial investigating perioperative chemotherapy demonstrated a survival benefit for gastric cancer patients. Finally, in Asia, the ACTS-GC and CLASSIC trials investigating postoperative chemotherapy established this as the standard of care after primary surgery that included D2 dissection. It is clear, however, that surgery alone is insufficient to achieve the highest possible cure rates.
Current Oncology Reports 01/2013; · 2.55 Impact Factor
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ABSTRACT: Gastric cancer continues to be a fatal disease with majority of cases presenting in late stages. For patients with advanced disease, we can only recommend palliative therapy. For localized gastric cancer, the approaches vary in various regions of the world. In western countries, preoperative chemotherapy or adjuvant chemo-radiation is preferred; however in Asia, surgery followed by adjuvant chemotherapy is favored. The extent of the lymph node dissection also varies by region. D2 gastrectomy is difficult to implement in most western countries while it is standardized and is a routine in Asia. We recommend multidisciplinary evaluation of each patient before starting any therapy. The prognosis after resection depends of the pathologic stage. Long-term survivors are often <50% in the West and <70% in many Asian countries. Regional and systemic recurrences are common. Improved systemic treatments are needed. Detailed studies of molecular biology might uncover novel therapeutic targets and prognostic subgroups. J. Surg. Oncol © 2013 Wiley Periodicals, Inc.
Journal of Surgical Oncology 01/2013; · 2.10 Impact Factor
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Journal of the National Comprehensive Cancer Network: JNCCN 12/2012; 10(12):1590-1592. · 4.41 Impact Factor
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ABSTRACT: Cancers of the oesophagus, gastro-oesophageal junction and stomach (upper gastrointestinal tract cancers; UGICs) pose a major health risk around the world. Collectively, the 5-year survival rate has remained <15%, and therapeutic improvements have been very slow and small. Novel molecules for early diagnosis, prognosis and therapy are, therefore, urgently needed. The role that microRNA (miRNA) molecules have in UGICs are worth pursuing to this end. miRNAs are small noncoding RNA molecules that regulate ∼60% of coding genes in humans and, therefore, are pivotal in mediating and regulating many physiologic processes. miRNAs are deregulated in many disease states, particularly in cancer, making them important targets. Here, we review the growing body of evidence regarding the alterations of miRNAs in UGICs. By suppressing translation and/or promoting degradation of mRNAs, miRNAs can contribute to carcinogenesis and progression of UGICs. In-depth studies of miRNAs in UGICs might yield novel insights and potential novel therapeutic strategies.
Nature Reviews Gastroenterology & Hepatology 11/2012; · 8.10 Impact Factor
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Leonard L Gunderson,
Kathryn A Winter, Jaffer A Ajani,
John E Pedersen,
Jennifer Moughan,
Al B Benson,
Charles R Thomas,
Robert J Mayer,
Michael G Haddock,
Tyvin A Rich,
Christopher G Willett
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ABSTRACT: PURPOSEOn initial publication of GI Intergroup Radiation Therapy Oncology Group (RTOG) 98-11 [A Phase III Randomized Study of 5-Fluorouracil (5-FU), Mitomycin, and Radiotherapy Versus 5-Fluorouracil, Cisplatin and Radiotherapy in Carcinoma of the Anal Canal], concurrent chemoradiation (CCR) with fluorouracil (FU) plus mitomycin (MMC) decreased colostomy failure (CF) when compared with induction plus concurrent FU plus cisplatin (CDDP), but did not significantly impact disease-free survival (DFS) or overall survival (OS) for anal canal carcinoma. The intent of the updated analysis was to determine the long-term impact of treatment on survival (DFS, OS, colostomy-free survival [CFS]), CF, and relapse (locoregional failure [LRF], distant metastasis) in this patient group. PATIENTS AND METHODS
Stratification factors included sex, clinical node status, and primary size. DFS and OS were estimated univariately by the Kaplan-Meier method, and treatment arms were compared by log-rank test. Time to relapse and CF were estimated by the cumulative incidence method and treatment arms were compared by using Gray's test. Multivariate analyses used Cox proportional hazard models to test for treatment differences after adjusting for stratification factors.ResultsOf 682 patients accrued, 649 were analyzable for outcomes. DFS and OS were statistically better for RT + FU/MMC versus RT + FU/CDDP (5-year DFS, 67.8% v 57.8%; P = .006; 5-year OS, 78.3% v 70.7%; P = .026). There was a trend toward statistical significance for CFS (P = .05), LRF (P = .087), and CF (P = .074). Multivariate analysis was statistically significant for treatment and clinical node status for both DFS and OS, for tumor diameter for DFS, and for sex for OS. CONCLUSIONCCR with FU/MMC has a statistically significant, clinically meaningful impact on DFS and OS versus induction plus concurrent FU/CDDP, and it has borderline significance for CFS, CF, and LRF. Therefore, RT + FU/MMC remains the preferred standard of care.
Journal of Clinical Oncology 11/2012; · 18.37 Impact Factor
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Gastrointestinal cancer research: GCR 11/2012; 5(6):203-4.
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Gastrointestinal endoscopy 11/2012; 76(5):1073-5. · 6.71 Impact Factor
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ABSTRACT: Paraneoplastic neurological syndromes (PNS) are associated with small-cell lung cancer, breast and gynecological cancers. We describe a gastric neoplasm presented with neurological symptoms. A 74-year-old male presented with tonic–clonic seizures. Initial investigations were normal; however, brain magnetic resonance imaging showed abnormal signal intensity in the hippocampi. A diagnosis of PNS was suspected. The patient was then diagnosed with a gastric neuroendocrine carcinoma with N-type voltage-gated calcium channel antibodies. The neurological impairments improved after the primary was resected and the patient remains free of cancer and paraneoplastic syndrome. We reviewed 10 cases of PNS associated with gastric cancer and found several characteristics: (1) older men, (2) neuroendocrine component or predominance, (3) oncological outcome for patients with PNS is better than for patients without PNS, and (4) neurological impairment is diagnosed 6 months prior to the diagnosis of gastric malignancy. In conclusion, elderly men with symptoms suggestive of PNS should be investigated for a gastric neuroendocrine malignancy.
Clinical Journal of Gastroenterology 10/2012; 5(5):355-360.
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Heath D Skinner,
Matthew R McCurdy,
Alfredo E Echeverria,
Steven H Lin,
James W Welsh,
Michael S O'Reilly,
Wayne L Hofstetter, Jaffer A Ajani,
Ritsuko Komaki,
James D Cox,
Vlad C Sandulache,
Jeffrey N Myers,
Thomas M Guerrero
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ABSTRACT: Background. We investigated the radiographic and pathologic response rate of esophageal adenocarcinoma treated with neoadjuvant chemoradiation in patients taking metformin. Material and methods. Two hundred eighty-five patients with esophageal adenocarcinoma treated with concurrent chemoradiation (CRT) followed by esophagectomy from 1997 to 2012 were included in the study, including 29 diabetics taking metformin, 21 diabetics not taking metformin and 235 non-diabetics. Pre- and post-treatment positron emission tomography (PET) scans were available for 204 patients. Pathologic response was graded at the time of surgery. Response rates were compared using both the χ(2) statistic as well as ANOVA with post-hoc LSD analysis. Multivariate logistic regression analysis was performed to control for predictors of pathologic complete response (CR) after CRT. Results. The overall rate of pathologic CR for the study population was 20%. The pathologic CR rate was higher in patients taking metformin (34.5%), compared to diabetic patients not taking metformin (4.8%, p = 0.01) and non-diabetic patients (19.6%, p = 0.05). Pathologic CR was related to metformin dose, with ≥1500 mg/d associated with a higher CR rate. No significant difference seen in pre-CRT maximum tumor SUV (p = 0.93), however post-CRT maximum SUV was significantly decreased in patients taking metformin (p = 0.05). On multivariate logistic regression, metformin use was independently associated with pathologic CR (p = 0.04). Metformin use was also associated with decreased in field loco-regional failure following radiation (p = 0.05). Conclusion. Metformin use is associated with a dose-dependent increased response to CRT in esophageal cancer and may be a sensitizer to this therapy.
Acta oncologica (Stockholm, Sweden) 09/2012; · 2.27 Impact Factor
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Takashi Taketa,
Arlene M Correa,
Akihiro Suzuki,
Mariela A Blum,
Pamela Chien,
Jeffrey H Lee,
James Welsh,
Steven H Lin,
Dipen M Maru,
Jeremy J Erasmus,
Manoop S Bhutani,
Brian Weston,
David C Rice,
Ara A Vaporciyan,
Wayne L Hofstetter,
Stephen G Swisher, Jaffer A Ajani
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ABSTRACT: Background: For patients with localized esophageal cancer (EC) who can withstand surgery, the preferred therapy is chemoradiation followed by surgery (trimodality). However, after achieving a clinical complete response [clinCR; defined as both post-chemoradiation endoscopic biopsy showing no cancer and physiologic uptake by positron emission tomography (PET)], some patients decline surgery. The literature on the outcome of such patients is sparse. Method: Between 2002 and 2011, we identified 622 trimodality-eligible EC patients in our prospectively maintained databases. All patients had to be trimodality eligible and must have completed preoperative staging after chemoradiation that included repeat endoscopic biopsy and PET among other routine tests. Results: Out of 622 trimodality-eligible patients identified, 61 patients (9.8%) declined surgery. All 61 patients had a clinCR. The median age was 69 years (range 47-85). Males (85.2%) and Caucasians (88.5%) were dominant. Baseline stage was II (44.2%) or III (52.5%), and histology was adenocarcinoma (65.6%) or squamous cell carcinoma (29.5%). Forty-two patients are alive at a median follow-up of 50.9 months (95% CI 39.5-62.3). The 5-year overall and relapse-free survival rates were 58.1 ± 8.4 and 35.3 ± 7.6%, respectively. Of 13 patients with local recurrence during surveillance, 12 had successful salvage resection. Conclusion: Although the outcome of 61 EC patients with clinCR who declined surgery appears reasonable, in the absence of a validated prediction/prognosis model, surgery must be encouraged for all trimodality-eligible patients.
Oncology 09/2012; 83(5):300-304. · 2.27 Impact Factor
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Jenifer L Marks,
Wayne Hofstetter,
Arlene M Correa,
Reza J Mehran,
David Rice,
Jack Roth,
Garrett Walsh,
Ara Vaporciyan,
Jeremy Erasmus,
Joe Chang,
Dipen Maru,
Jeffrey H Lee,
Jared Lee, Jaffer A Ajani,
Stephen G Swisher
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ABSTRACT: Outcomes of salvage esophagectomy after definitive chemoradiation (CRT) for squamous cell carcinoma are well defined. Previous reports of salvage esophagectomy in patients with recurrent adenocarcinoma after definitive CRT are limited by small numbers and high morbidity and mortality rates.
We reviewed our experience of 65 patients with esophageal adenocarcinoma treated from 1997 to 2010 who underwent salvage esophagectomy after failed definitive CRT. We then compared this group to 65 matched patients of 521 total patients with esophageal adenocarcinoma who received preoperative CRT followed by planned esophagectomy. Propensity matching and multivariable analysis were performed.
Median time to surgery from completion of therapy for the salvage group was 216 days. Major postoperative events (major pulmonary event, conduit loss, leak, readmission to intensive care unit) occurred in 35% (23 of 65) of salvage patients and 31% (20 of 65) of the planned resection matched group. Anastomotic leak occurred in 18.5% (12 of 65) and 11.3 (59 of 521) of salvage and planned groups, respectively. Thirty-day mortality was 3.1% (2 of 65) after salvage resection and 4.6% (3 of 65) after planned resection. There was no difference in 3-year overall or median survival between the two groups of patients (32 months, 48% salvage, versus 40 months, 57% planned resection). Multivariable analysis did not identify salvage strategy or time from completion of therapy to resection as a predictor of major event or death.
Postoperative morbidity, mortality, and overall survival of patients after salvage esophagectomy are comparable to matched patients after planned resection. These results suggest that patients with esophageal adenocarcinoma who fail definitive CRT and recur locoregionally should be considered for salvage esophagectomy at experienced esophageal centers.
The Annals of thoracic surgery 08/2012; 94(4):1126-33. · 3.74 Impact Factor
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ABSTRACT: PURPOSE: Although 3-dimensional conformal radiotherapy (3D-CRT) is the worldwide standard for the treatment of esophageal cancer, intensity modulated radiotherapy (IMRT) improves dose conformality and reduces the radiation exposure to normal tissues. We hypothesized that the dosimetric advantages of IMRT should translate to substantive benefits in clinical outcomes compared with 3D-CRT. METHODS AND MATERIALS: An analysis was performed of 676 nonrandomized patients (3D-CRT, n=413; IMRT, n=263) with stage Ib-IVa (American Joint Committee on Cancer 2002) esophageal cancers treated with chemoradiotherapy at a single institution from 1998-2008. An inverse probability of treatment weighting and inclusion of propensity score (treatment probability) as a covariate were used to compare overall survival time, interval to local failure, and interval to distant metastasis, while accounting for the effects of other clinically relevant covariates. The propensity scores were estimated using logistic regression analysis. RESULTS: A fitted multivariate inverse probability weighted-adjusted Cox model showed that the overall survival time was significantly associated with several well-known prognostic factors, along with the treatment modality (IMRT vs 3D-CRT, hazard ratio 0.72, P<.001). Compared with IMRT, 3D-CRT patients had a significantly greater risk of dying (72.6% vs 52.9%, inverse probability of treatment weighting, log-rank test, P<.0001) and of locoregional recurrence (P=.0038). No difference was seen in cancer-specific mortality (Gray's test, P=.86) or distant metastasis (P=.99) between the 2 groups. An increased cumulative incidence of cardiac death was seen in the 3D-CRT group (P=.049), but most deaths were undocumented (5-year estimate, 11.7% in 3D-CRT vs 5.4% in IMRT group, Gray's test, P=.0029). CONCLUSIONS: Overall survival, locoregional control, and noncancer-related death were significantly better after IMRT than after 3D-CRT. Although these results need confirmation, IMRT should be considered for the treatment of esophageal cancer.
International journal of radiation oncology, biology, physics 08/2012; · 4.59 Impact Factor
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Yuki Hayashi,
Lianchun Xiao,
Akihiro Suzuki,
Mariela A Blum,
Bradley Sabloff,
Takashi Taketa,
Dipen M Maru,
James Welsh,
Steven H Lin,
Brian Weston,
Jeffrey H Lee,
Manoop S Bhutani,
Wayne L Hofstetter,
Stephen G Swisher, Jaffer A Ajani
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ABSTRACT: BACKGROUND: The presence of malignant lymph nodes (+ypNodes) in the surgical specimen after preoperative chemoradiation (trimodality) in patients with oesophageal cancer (EC) portends a poor prognosis for overall survival (OS) and disease-free survival (DFS). Currently, none of the clinical variables highly correlates with +ypNodes. We hypothesised that a combination of clinical variables could generate a model that associates with high likelihood of +ypNodes after trimodality in EC patients. METHODS: We report on 293 consecutive EC patients who received trimodality therapy. A multivariate logistic regression analysis that included pretreatment and post-chemoradiation variables identified independent variables that were used to construct a nomogram for +ypNodes after trimodality in EC patients. RESULTS: Of 293 patients, 91 (31.1%) had +ypNodes. OS (p=0.0002) and DFS (p<0.0001) were shorter in patients with +ypNodes compared to those with -ypNodes. In multivariable analysis, the significant variables for +ypNodes were: baseline T-stage (odds ratio [OR], 7.145; 95% confidence interval [CI], 1.381-36.969; p=0.019), baseline N-stage (OR, 2.246; 95% CI, 1.024-4.926; p=0.044), tumour length (OR, 1.178; 95% CI, 1.024-1.357; p=0.022), induction chemotherapy (OR, 0.471; 95% CI, 0.242-0.915; p=0.026), nodal uptake on post-chemoradiation positron emission tomography (OR, 2.923; 95% CI, 1.007-8.485; p=0.049) and enlarged node(s) on post-chemoradiation computerised tomography (OR, 3.465; 95% CI, 1.549-7.753; p=0.002). The nomogram after internal validation using the bootstrap method (200 runs) yielded a high concordance index of 0.756. CONCLUSION: Our nomogram highly correlates with the presence of +ypNodes after chemoradiation, however, considerably more refinement is needed before it can be implemented in the clinic.
European journal of cancer (Oxford, England: 1990) 07/2012; · 4.12 Impact Factor
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Nature Reviews Clinical Oncology 07/2012; 9(9):493-4. · 11.96 Impact Factor
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Yonghui Wu,
Heike Grabsch,
Tatiana Ivanova,
Iain Beehuat Tan,
Jacinta Murray,
Chia Huey Ooi,
Alexander Ian Wright,
Nicholas P West,
Gordon G A Hutchins,
Jeanie Wu, [......],
Nicole van Grieken,
Bauke Ylstra,
Sun Young Rha, Jaffer A Ajani,
Jae Ho Cheong,
Sung Hoon Noh,
Kiat Hon Lim,
Alex Boussioutas,
Ju-Seog Lee,
Patrick Tan
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ABSTRACT: OBJECTIVE: Gastric adenocarcinoma (gastric cancer, GC) is a major cause of global cancer mortality. Identifying molecular programmes contributing to GC patient survival may improve our understanding of GC pathogenesis, highlight new prognostic factors and reveal novel therapeutic targets. The authors aimed to produce a comprehensive inventory of gene expression programmes expressed in primary GCs, and to identify those expression programmes significantly associated with patient survival. DESIGN: Using a network-modelling approach, the authors performed a large-scale meta-analysis of GC transcriptome data integrating 940 gastric transcriptomes from multiple independent patient cohorts. The authors analysed a training set of 428 GCs and 163 non-malignant gastric samples, and a validation set of 288 GCs and 61 non-malignant gastric samples. RESULTS: The authors identified 178 gene expression programmes ('modules') expressed in primary GCs, which were associated with distinct biological processes, chromosomal location patterns, cis-regulatory motifs and clinicopathological parameters. Expression of a transforming growth factor β (TGF-β) signalling associated 'super-module' of stroma-related genes consistently predicted patient survival in multiple GC validation cohorts. The proportion of intra-tumoural stroma, quantified by morphometry in tissue sections from gastrectomy specimens, was also significantly associated with stromal super-module expression and GC patient survival. CONCLUSION: Stromal gene expression predicts GC patient survival in multiple independent cohorts, and may be closely related to the intra-tumoural stroma proportion, a specific morphological GC phenotype. These findings suggest that therapeutic approaches targeting the GC stroma may merit evaluation.
Gut 06/2012; · 10.11 Impact Factor
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Akihiro Suzuki,
Lianchun Xiao,
Takashi Taketa,
Mariela A Blum,
Aurelio Matamoros,
Pamela L Chien,
Paul F Mansfield,
Keith F Fournier,
Brian Weston,
Jeffrey H Lee,
Manoop S Bhutani,
Jeannelyn S Estrella,
Marc E Delclos,
Sunil Krishnan,
Prajnan Das, Jaffer A Ajani
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ABSTRACT: In patients with localized gastric cancer (LGC) who are unfit for surgery, decline surgery, or have unresectable cancer, chemoradiotherapy may provide palliation; however, data in the literature are sparse.
We identified 66 LGC patients who had definitive chemoradiation but no surgery. All patients had baseline and postchemoradiation staging including an endoscopic biopsy. Multiple statistical methods were used to analyze outcomes.
Most patients were men and most had stage III or IV cancer. Five patients were surgery eligible but declined to have surgery. The median follow-up time was 33.9 months (95% CI 18.3-49.6). The median survival time (MST) for 66 patients was only 14.5 months (95% CI 10.8-19.7) and the median relapse-free survival (RFS) was 5.03 months (95% CI 4.67-6.40). The estimated overall survival (OS) and RFS rates at 3 years were 22.6% (95% CI 13.7-37.3) and 7.7% (95% CI 3.2-18.6), respectively. Twenty-three (35%) patients who achieved a clinical complete response (cCR; negative postchemoradiation biopsy and no progression by imaging) fared better than those who achieved less than cCR (<cCR) [cCR: MST 30.7 months (95% CI 20.4-NA); <cCR: MST 10.6 months (95% CI 8.43-14.9); p < 001]. In multivariate analysis, cCR was the only independent prognosticator for OS [hazard ratio (HR) = 0.32, p < 0.0012] and RFS (HR = 0.12, p < 0.0001).
Our data demonstrate that in the absence of surgery, outcomes with definitive chemoradiation are only modest. A third of the patients achieved cCR and had a longer OS and RFS than those who achieved <cCR.
Oncology 06/2012; 82(6):347-51. · 2.27 Impact Factor
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ABSTRACT: Local failure after definitive chemoradiation therapy for unresectable esophageal cancer remains problematic. Little is known about the failure pattern based on modern-day radiation treatment volumes. We hypothesized that most local failures would be within the gross tumor volume (GTV), where the bulk of the tumor burden resides.
We reviewed treatment volumes for 239 patients who underwent definitive chemoradiation therapy and compared this information with failure patterns on follow-up positron emission tomography (PET). Failures were categorized as within the GTV, the larger clinical target volume (CTV, which encompasses microscopic disease), or the still larger planning target volume (PTV, which encompasses setup variability) or outside the radiation field.
At a median follow-up time of 52.6 months (95% confidence interval, 46.1-56.7 months), 119 patients (50%) had experienced local failure, 114 (48%) had distant failure, and 74 (31%) had no evidence of failure. Of all local failures, 107 (90%) were within the GTV, 27 (23%) were within the CTV, and 14 (12%) were within in the PTV. On multivariate analysis, GTV failure was associated with tumor status (T3/T4 vs T1/T2; odds ratio, 6.35; P = .002), change in standardized uptake value on PET before and after treatment (decrease >52%: odds ratio, 0.368; P = .003), and tumor size (>8 cm, 4.08; P = .009).
Most local failures after definitive chemoradiation for unresectable esophageal cancer occur in the GTV. Future therapeutic strategies should focus on enhancing local control.
Cancer 05/2012; 118(10):2632-40. · 4.77 Impact Factor
