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ABSTRACT: High-level microsatellite instability (MSI-high) is found in approximately 15% of all colorectal adenocarcinomas (CRCs) and in at least 20% of right-sided cancers. It is most commonly due to somatic hypermethylation of the MLH1 gene promoter region, with familial cases (Lynch syndrome) representing only 2% to 3% of CRCs overall. In contrast to CRC, MSI-high in appendiceal adenocarcinomas is rare. Only 4 MSI-high appendiceal carcinomas and 1 MSI-high appendiceal serrated adenoma have been previously reported, and the prevalence of MSI in the appendix is unknown. We identified 108 appendiceal carcinomas from MD Anderson Cancer Center in which MSI status had been assessed by immunohistochemistry for the DNA mismatch-repair proteins MLH1, MSH2, MSH6, and PMS2 (n=83), polymerase chain reaction (n=7), or both (n=18). Three cases (2.8%) were MSI-high, and 1 was MSI-low. The 3 MSI-high cases included: (1) a poorly differentiated nonmucinous adenocarcinoma with loss of MLH1/PMS2 expression, lack of MLH1 promoter methylation, and lack of BRAF gene mutation, but no detected germline mutation in MLH1 from a 39-year-old man; (2) an undifferentiated carcinoma with loss of MSH2/MSH6, but no detected germline mutation in MSH2 or TACSTD1, from a 59-year-old woman; and (3) a moderately differentiated mucinous adenocarcinoma arising in a villous adenoma with loss of MSH2/MSH6 expression, in a 38-year-old man with a strong family history of CRC who declined germline testing. When the overall group of appendiceal carcinomas was classified according to histologic features and precursor lesions, the frequencies of MSI-high were: 3 of 108 (2.8%) invasive carcinomas, 3 of 96 (3.1%) invasive carcinomas that did not arise from a background of goblet cell carcinoid tumors, and 0 of 12 (0%) signet ring and mucinous carcinomas arising in goblet cell carcinoid tumors. These findings, in conjunction with the previously reported MSI-high appendiceal carcinomas, highlight the low prevalence of MSI in the appendix as compared with the right colon and suggest that MLH1 promoter methylation is not a mechanism for MSI in this location.
The American journal of surgical pathology 05/2013; · 4.06 Impact Factor
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Acta oncologica (Stockholm, Sweden) 10/2012; · 2.27 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: Introduction:Although sentinel lymph node (SLN) status is the most powerful predictor of prognosis in patients with clinically localized melanoma, a proportion of melanoma patients with histologically negative SLNs will still recur. It is hypothesized that tumor response may be altered or mediated by specific cytokines. We therefore investigated whether levels of IL-4, IL-6, IL-10, TNF-, or IFN- would predict disease recurrence in melanoma patients with histologically negative SLNs.Methods:This prospective cohort study involved 218 patients with clinically localized melanoma who underwent a histologically negative SLN biopsy. Preoperative plasma cytokine levels were determined by enzyme-linked immunosorbent assay on these patients, as well as on 90 healthy controls. Kaplan-Meier life tables were constructed, and Cox proportional hazards analyses were performed to assess predictors of disease-free survival (DFS).Results:At a median follow-up of 43 months, 33 of 218 patients (15%) had suffered disease recurrence. Melanoma patients had significant elevations of IL-4, IL-6, and IL-10 compared to healthy controls; levels of IFN- were less elevated in melanoma patients compared to controls. Despite this, melanoma patients with detectable IFN- levels were at significantly higher risk for recurrence compared to patients with undetectable levels (5-year DFS 70% vs. 86%, P = .03). On multivariate analysis including standard melanoma prognostic factors, only tumor thickness (P = .004) and the presence of detectable IFN- levels (P = .05) were significant independent prognostic factors for disease-free survival.Conclusions:Among melanoma patients with clinically localized disease who have undergone a histologically negative SLN biopsy, presence of a detectable plasma level of IFN- is an independent predictor of disease recurrence. Elevated levels of IFN- may identify a group of early-stage melanoma patients who are more likely to have recurrence of disease and who may benefit from adjuvant therapies, including immunotherapies.
Annals of Surgical Oncology 04/2012; 8(2):116-122. · 4.17 Impact Factor
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ABSTRACT: BackgroundIncreased interferon γ (IFN-γ) levels are an independent predictor of melanoma recurrence. Human leukocyte antigen (HLA) class
II genes can regulate cytokine production; we investigated whether these genes would predict IFN-γ levels and recurrence in
melanoma patients.
MethodsOf 591 patients who presented with localized melanoma, 579 underwent identification of HLA class II alleles; 233 melanoma
patients and 90 controls underwent determination of plasma IFN-γ levels. HLA class II genes were examined for association
with IFN-γ levels and disease recurrence.
ResultsAfter a median follow-up of 60 months, melanoma patients with IFN-γ levels above the mean control value were more likely to
have developed disease recurrence compared with patients with levels below the mean. The HLA class II geneHLA-DRB1*1101 was the strongest predictor of recurrence, andHLA-DRB1*1101-positive melanoma patients had increased levels of IFN-γ compared with patients lacking the gene.
ConclusionsAmong patients with localized melanoma, bothHLA-DRB1*1101 and increased IFN-γ levels were associated with an increased risk for recurrence;HLA-DRB1*1101-positive patients had relatively increased levels of IFN-γ. HLA class II genes may mediate cytokine production in melanoma
patients, and this mechanism may help determine the risk of disease recurrence.
Annals of Surgical Oncology 04/2012; 9(6):587-593. · 4.17 Impact Factor
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Twisha Chakravarty,
Christopher H Crane,
Jaffer A Ajani, Paul F Mansfield,
Tina M Briere,
A Sam Beddar,
Henry Mok,
Valerie K Reed,
Sunil Krishnan,
Marc E Delclos,
Prajnan Das
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ABSTRACT: The goal of this study was to evaluate dosimetric parameters, acute toxicity, pathologic response, and local control in patients treated with preoperative intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy for localized gastric adenocarcinoma.
Between November 2007 and April 2010, 25 patients with localized gastric adenocarcinoma were treated with induction chemotherapy, followed by preoperative IMRT and concurrent chemotherapy and, finally, surgical resection. The median radiation therapy dose was 45 Gy. Concurrent chemotherapy was 5-fluorouracil and oxaliplatin in 18 patients, capecitabine in 3, and other regimens in 4. Subsequently, resection was performed with total gastrectomy in 13 patients, subtotal gastrectomy in 7, and other surgeries in 5.
Target coverage, expressed as the ratio of the minimum dose received by 99% of the planning target volume to the prescribed dose, was a median of 0.97 (range, 0.92-1.01). The median V(30) (percentage of volume receiving at least 30 Gy) for the liver was 26%; the median V(20) (percentage of volume receiving at least 20 Gy) for the right and left kidneys was 14% and 24%, respectively; and the median V(40) (percentage of volume receiving at least 40 Gy) for the heart was 18%. Grade 3 acute toxicity developed in 14 patients (56%), including dehydration in 10, nausea in 8, and anorexia in 5. Grade 4 acute toxicity did not develop in any patient. There were no significant differences in the rates of acute toxicity, hospitalization, or feeding tube use in comparison to those in a group of 50 patients treated with preoperative three-dimensional conformal radiation therapy with concurrent chemotherapy. R0 resection was obtained in 20 patients (80%), and pathologic complete response occurred in 5 (20%).
Preoperative IMRT for gastric adenocarcinoma was well tolerated, accomplished excellent target coverage and normal structure sparing, and led to appropriate pathologic outcomes.
International journal of radiation oncology, biology, physics 12/2011; 83(2):581-6. · 4.59 Impact Factor
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ABSTRACT: The understanding and management of lymphomas have evolved significantly over the past decade. Among the most important changes
have been the development of new classification systems that include molecular determinants, identification of etiologic factors
for mucosa-associated lymphomas (and their implications for management), demonstration of the importance of T cells in the
progression of B-cell lymphomas, development of an international tumor scoring system to better determine prognosis, and establishment
of bone marrow transplant as effective therapy in relapsed non-Hodgkin’s lymphoma. This chapter explores these issues and
their implications for the practicing oncologist.
04/2011: pages 203-211;
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ABSTRACT: Most patients with localized gastric cancer require multimodality therapy. Surgery is the primary treatment for localized gastric cancer, although controversy exists about the optimal extent of lymphadenectomy in these patients. Recent studies have evaluated the role of laparoscopic surgery and endoscopic mucosal resection in selected patients. Multimodality treatment options for these patients include post-operative chemoradiation and perioperative chemotherapy. The Intergroup 0116 trial demonstrated that patients treated with surgery and post-operative chemoradiation had significantly higher overall survival compared to patients treated with surgery alone. The MAGIC trial showed that patients treated with perioperative epirubicin, cisplatin, and 5-fluorouracil had significantly higher overall survival compared to patients treated with surgery alone. Other recent trials have evaluated the roles of preoperative chemoradiation and adjuvant chemotherapy. Multidisciplinary evaluation plays a crucial role in the management of these patients.
Journal of the National Comprehensive Cancer Network: JNCCN 04/2010; 8(4):417-25. · 4.41 Impact Factor
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Tawnya L Bowles,
Yan Xing,
Chung-Yuan Hu,
Kristi S Mungovan,
Robert L Askew,
George J Chang,
Jeffrey E Gershenwald,
Jeffrey E Lee, Paul F Mansfield,
Merrick I Ross,
Janice N Cormier
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ABSTRACT: Conditional survival estimates provide useful prognostic information for cancer survivors. The objective of this study was to determine conditional survival estimates for melanoma patients with substages of stage III disease.
A retrospective analysis of 760 patients who underwent lymphadenectomy for node-positive melanoma was conducted, and patients were stratified into substages: IIIA, IIIB, and IIIC. The 5-year conditional disease-free survival (DFS) and disease-specific survival (DSS) were calculated following lymphadenectomy using the methods of Kaplan and Meier and were reassessed for survivors on an annual basis. Multivariate Cox regression models were used to calculate adjusted conditional DFS and DSS accounting for age, gender, tumor histology, and extracapsular extension.
For patients with IIIA, IIIB, and IIIC disease, 5-year conditional DSS from treatment to year 5 improved from 78% to 90%, 54% to 79%, and 39% to 78%, respectively. For 5-year conditional DFS over the same period, the estimates increased from 65% to 79%, 37% to 81%, and 26% to 92%, respectively. Male patients experienced decreased 5-year conditional DSS and DFS across all substages, with the most pronounced effect on DSS in stage IIIC. Multivariate analysis demonstrated that survival differences among stage IIIC patients based on histologic subtype and extracapsular extension decreased over time.
Conditional survival estimates are more optimistic and realistic for cancer survivors than traditional survival estimates over time. For node-positive melanoma survivors, 5-year conditional DFS and DSS improve significantly over time. These estimates are critical to treatment decisions and non-treatment-related planning for both clinicians and patients.
Annals of Surgical Oncology 04/2010; 17(8):2015-23. · 4.17 Impact Factor
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ABSTRACT: Conditional survival (CS) has emerged as a clinically relevant measure of prognosis for cancer survivors. The objective of this analysis was to provide melanoma-specific CS estimates to help clinicians promote more informed patient decision making.
Patients with melanoma and at least 5 years of follow-up were identified from the Surveillance Epidemiology and End Results registry (1988-2000). By using the methods of Kaplan and Meier, stage-specific, 5-year CS estimates were independently calculated for survivors for each year after diagnosis. Stage-specific multivariate Cox regression models including baseline survivor functions were used to calculate adjusted melanoma-specific CS for different subgroups of patients further stratified by age, gender, race, marital status, anatomic tumor location, and tumor histology.
Five-year CS estimates for patients with stage I disease remained constant at 97% annually, while for patients with stages II, III, and IV disease, 5-year CS estimates from time 0 (diagnosis) to 5 years improved from 72% to 86%, 51% to 87%, and 19% to 84%, respectively. Multivariate CS analysis revealed that differences in stages II through IV CS based on age, gender, and race decreased over time.
Five-year melanoma-specific CS estimates improve dramatically over time for survivors with advanced stages of disease. These prognostic data are critical to patients for both treatment and nontreatment related life decisions.
Cancer 02/2010; 116(9):2234-41. · 4.77 Impact Factor
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ABSTRACT: Glycoprotein-96, a non-polymorphic heat-shock protein, associates with intracellular peptides. Autologous tumor-derived heat shock protein-peptide complex 96 (HSPPC-96) can elicit potent tumor-specific T cell responses and protective immunity in animal models. We sought to investigate the feasibility, safety, and antitumor activity of HSPPC-96 vaccines prepared from tumor specimens of patients with metastatic melanoma.
Patients with a Karnofsky Performance Status >70% and stage III or stage IV melanoma had to have a metastasis >3 cm in diameter resectable as part of routine clinical management. HSPPC-96 tumor-derived vaccines were prepared in one of three dose levels (2.5, 25, or 100 microg/dose) and administered as an intradermal injection weekly for 4 consecutive weeks. In vivo induction of immunity was evaluated using delayed-type hypersensitivity (DTH) to HSPPC-96, irradiated tumor, and dinitrochlorobenzene (DNCB). The gamma-interferon (IFNgamma) ELISPOT assay was used to measure induction of a peripheral blood mononuclear cell response against autologous tumor cells at baseline and at the beginning of weeks 3, 4, and 8.
Among 36 patients enrolled, 72% had stage IV melanoma and 83% had received prior systemic therapy. The smallest tumor specimen from which HSPPC-96 was prepared weighed 2 g. Twelve patients (including 9 with stage IV and indicator lesions) had a negative DNCB skin test result at baseline. All 36 patients were treated and evaluable for toxicity and response. There were no serious toxicities. There were no observed DTH responses to HSPPC-96 or to autologous tumor cells before or during treatment. The IFNgamma-producing cell count rose modestly in 5 of 26 patients and returned to baseline by week 8, with no discernible association with HSPPC-96 dosing or clinical parameters. There were no objective responses among 16 patients with stage IV disease and indicator lesions. Among 20 patients treated in the adjuvant setting, 11 with stage IV melanoma at baseline had a progression-free and overall survival of 45% and 82%, respectively, with a median follow-up of 10 years.
Treatment with autologous tumor-derived HSPPC-96 was feasible and safe at all doses tested. Observed immunological effects and antitumor activity were modest, precluding selection of a biologically active dose. Nevertheless, the 25-microg dose level was shown to be practical for further study.
Journal of Translational Medicine 01/2010; 8:9. · 3.41 Impact Factor
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ABSTRACT: Appendiceal neoplasms include tumors ranging from benign-appearing cells with widespread mucin deposits to aggressive poorly differentiated signet ring cell adenocarcinomas. Traditionally, these tumors are treated with cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy. For some patients, cytoreductive surgery is not an option, and minimal published data exist in the management and outcome of these patients. A retrospective analysis was conducted to determine the benefit of modern systemic chemotherapy in patients with disseminated appendiceal neoplasm who were not considered optimal candidates for cytoreductive surgery.
A retrospective review was conducted using The University of Texas M. D. Anderson Cancer Center tumor registry between January 2000 and July 2005. Response was determined by radiographic response and/or overall clinical benefit.
Of 186 patients diagnosed with appendiceal neoplasm, 54 (29%) patients considered to be suboptimal surgical candidates received > or =2 cycles of systemic chemotherapy. Thirty (55.6%) patients had a disease control rate noted as a complete response, partial response, or stable disease. After a median follow-up of 24 months, the median progression-free survival (PFS) and overall survival were determined to be 7.6 months (95% confidence interval [CI], 4-11) and 56 months (95% CI, 36-not applicable), respectively.
Systemic chemotherapy has a role in appendiceal neoplasm patients who are suboptimal candidates for cytoreductive surgery. The intermediate PFS indicates the challenges that exist for appendiceal neoplasm patients in this setting. Prospective randomized trials including systemic chemotherapy are needed to provide further insight into this malignancy, for which no standard exists.
Cancer 11/2009; 116(2):316-22. · 4.77 Impact Factor
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Gastrointestinal cancer research: GCR 06/2009; 3(3):115-7.
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ABSTRACT: The objectives of this analysis were to compare various measures associated with lymph node (LN) dissection and to identify threshold values associated with disease-specific survival (DSS) outcomes in patients with melanoma.
Patients with lymph node-positive melanoma who underwent therapeutic LN dissection of the neck, axilla, and inguinal region were identified from the SEER database (1988-2005). We performed Cox multivariate analyses to determine the impact of the total number of LNs removed, number of negative LNs removed, and LN ratio on DSS. Multivariate cut-point analyses were conducted for each anatomic region to identify the threshold values associated with the largest improvement in DSS.
The LN ratio was significantly associated with DSS for all LN regions. The LN ratio thresholds resulting in the greatest difference in 5-year DSS were .07, .13, and .18 for neck, axillary, and inguinal regions, respectively, corresponding to 15, 8, and 6 LNs removed per positive lymph node. After adjustment for other clinicopathologic factors, the hazard ratios (HRs) were .53 (95% confidence interval [CI], .40 to .71) in the neck, .52 (95% CI, .42 to .65) in the axillary, and .47 (95% CI, .36 to .61) in the inguinal regions for patients who met the LN ratio threshold.
Among the prognostic factors examined, LN ratio was the best indicator of the extent of LN dissection, regardless of anatomic nodal region. These data provide evidence-based guidelines for defining adequate LN dissections in melanoma patients.
Cancer 04/2009; 115(11):2505-13. · 4.77 Impact Factor
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Kevin B Kim,
Sewa S Legha,
Rene Gonzalez,
Clay M Anderson,
Marcella M Johnson,
Ping Liu,
Nicholas E Papadopoulos,
Omar Eton,
Carl Plager,
Antonio C Buzaid, [......],
Wen-Jen Hwu,
Angela M Frost,
Gladys Alvarado,
Patrick Hwu,
Merrick I Ross,
Jeffrey E Gershenwald,
Jeffrey E Lee, Paul F Mansfield,
Robert S Benjamin,
Agop Y Bedikian
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ABSTRACT: The objective of this study was to compare the clinical benefit of biochemotherapy and interferon-alpha-2b (IFN) as adjuvant therapy. Biochemotherapy has higher response rates than other regimens in patients with metastatic melanoma. We conducted a randomized phase III study comparing the clinical benefit of biochemotherapy and IFN as adjuvant therapy. Patients who had undergone lymphadenectomy for melanoma metastatic to regional lymph nodes were randomly assigned to either biochemotherapy or IFN, and IFN patients were further randomized to either high-dose IFN (HDI) or intermediate-dose IFN (IDI). The primary end point was relapse-free survival (RFS); the secondary end point was overall survival (OS). The planned enrollment was 200 patients, the number required to have 80% power to detect, at a significance level of 5%, an improvement in median RFS from 18 to 36 months and an improvement in median OS from 40 to 80 months between the IFN and biochemotherapy groups. A futility analysis was performed because of slow accrual. One hundred and thirty-eight patients were enrolled - 71 in the biochemotherapy group, 34 in the HDI subgroup, and 33 in the IDI subgroup. No significant differences in median RFS or OS between the HDI and IDI subgroups were observed. With a median follow-up of 49.3 months, neither the biochemotherapy nor IFN group had reached median RFS or OS, and there were no significant differences in estimated median RFS or OS (P=0.86 and 0.45, respectively) between the two groups. Biochemotherapy is not more effective than IFN as adjuvant therapy for melanoma. These findings support early termination of this trial.
Melanoma research 03/2009; 19(1):42-9. · 2.06 Impact Factor
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ABSTRACT: To compare treatment-related outcomes and toxicity for patients with axillary lymph node metastases from malignant melanoma treated with postoperative radiation therapy (RT) to either the axilla only or both the axilla and supraclavicular fossa (extended field [EF]).
The medical records of 200 consecutive patients treated with postoperative RT for axillary lymph node metastases from malignant melanoma were retrospectively reviewed. All patients received postoperative hypofractionated RT for high-risk features; 95 patients (48%) received RT to the axilla only and 105 patients (52%) to the EF.
At a median follow-up of 59 months, 111 patients (56%) had sustained relapse, and 99 patients (50%) had died. The 5-year overall survival, disease-free survival, and distant metastasis-free survival rates were 51%, 43%, and 46%, respectively. The 5-year axillary control rate was 88%. There was no difference in axillary control rates on the basis of the treated field (89% for axilla only vs. 86% for EF; p = 0.4). Forty-seven patients (24%) developed treatment-related complications. On both univariate and multivariate analyses, only treatment with EF irradiation was significantly associated with increased treatment-related complications.
Adjuvant hypofractionated RT to the axilla only for metastatic malignant melanoma with high-risk features is an effective method to control axillary disease. Limiting the radiation field to the axilla only produced equivalent axillary control rates to EF and resulted in lower treatment-related complication rates.
International journal of radiation oncology, biology, physics 10/2008; 73(5):1376-82. · 4.59 Impact Factor
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ABSTRACT: We and others have demonstrated that additional positive lymph nodes (LNs) are identified in only 8% to 33% of patients with melanoma who have positive sentinel LNs (SLNs) and undergo complete therapeutic LN dissection (cTLND). We sought to determine predictors of additional regional LN involvement in patients with positive SLNs.
Patients with clinically node-negative melanoma who underwent SLN biopsy (1991 to 2003) and had positive SLNs were identified. Clinicopathologic factors, including extent of microscopic disease within SLNs, were evaluated as potential predictors of positive non-SLNs.
Overall, 359 (16.3%) of the 2,203 patients identified had a positive SLN. Positive non-SLNs were identified in 48 (14.0%) of the 343 patients with positive SLNs who underwent cTLND. On univariate analysis, several measures of SLN microscopic tumor burden, one versus three or more SLNs harvested, tumor thickness more than 2 mm, age older than 50 years, and Clark level higher than III were predictive of positive non-SLNs; primary tumor ulceration and number of positive SLNs had no apparent impact. On multivariable logistic regression analysis, measures of SLN microscopic tumor burden were the most significant independent predictors of positive non-SLNs; tumor thickness more than 2 mm and number of SLNs harvested also predicted additional disease. A model was developed that stratified patients according to their risk for non-SLN involvement.
In melanoma patients with positive SLNs, SLN tumor burden, primary tumor thickness, and number of SLNs harvested may be useful in identifying a group at low risk for positive non-SLNs and be spared the potential morbidity of a cTLND.
Journal of Clinical Oncology 08/2008; 26(26):4296-303. · 18.37 Impact Factor
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Valerie K Reed,
Sunil Krishnan, Paul F Mansfield,
Priya R Bhosale,
Michelle Kim,
Prajnan Das,
Nora A Janjan,
Marc E Delclos,
Andrew M Lowy,
Barry W Feig,
Peter W T Pisters,
Jaffer A Ajani,
Christopher H Crane
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ABSTRACT: To retrospectively determine the incidence and patterns (in-field, marginal, or out-of-field) of locoregional gastric cancer recurrence in patients who received preoperative chemoradiotherapy and to determine the outcome in these patients.
Between 1994 and 2004, 149 patients with gastric carcinoma were treated according to institutional protocols with preoperative chemoradiotherapy. Ultimately, 105 patients had an R0 resection. Of these 105 patients, 65 received preoperative chemotherapy followed by chemoradiotherapy and 40 received preoperative chemoradiotherapy. Most (96%) of these patients received 5-fluorouracil-based chemotherapy during radiotherapy, and the median radiation dose was 45 Gy. We retrospectively identified and classified the patterns of locoregional recurrence.
The 3-year actuarial incidence of locoregional recurrence was 13%, with locoregional disease recurring as any part of the failure pattern in 14 patients. Most (64%) of the evaluable locoregional recurrences were in-field. Of the 4 patients with a marginal recurrence, 2 had had inadequate coverage of the regional nodal volumes on their oblique fields. The pathologic complete response rate was 23%. A pathologic complete response was the only statistically significant predictor of locoregional control.
Patients with gastric cancer who received preoperative chemoradiotherapy had low rates of locoregional recurrence. This strategy merits prospective multi-institutional and randomized evaluation.
International Journal of Radiation OncologyBiologyPhysics 08/2008; 71(3):741-7. · 4.11 Impact Factor
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ABSTRACT: Regional-based studies have indicated that ethnicity is associated with presentation and outcome in patients with gastric adenocarcinoma. To validate this observation in a large cohort, the authors of this report used the National Cancer Data Base (NCDB) to determine whether self-reported ethnicity influences presentation and survival in this patient population.
Patient demographics, tumor-related features, and treatment-related features were analyzed by ethnicity. Univariate analyses were performed using the chi-square test. Overall median and relative survival rates were examined by using the Kaplan-Meier method. Cox proportional-hazards models were used to identify the predictors of survival outcomes.
Between 1995 and 2002, 81,095 cases of gastric adenocarcinoma were entered into the NCDB. There were 57,943 white patients (71.5%), 11,094 African-American patients (13.7%), 5665 Hispanic patients (7%), 4736 Asian/Pacific Islander (API) patients (5.8%), and 1657 patients of other ethnicities (2%). Significant differences were observed according to ethnicity among the variables that were compared (all P < .01). In patients with stage I and II disease, the 5-year relative survival rates for APIs (stage I, 77.2%; stage II, 48%) were more favorable than for whites (stage I, 58.7%; stage II, 32.8%), African Americans (stage I, 55.9%; stage II, 37.9%), and Hispanics (stage I, 60.8%; stage II, 39.3%). The overall median survival of APIs was more favorable than that of others (P < .01). Predictors of a better outcome were Asian race, female sex, younger age, earlier stage, lower grade, distal tumors, multimodality treatment, and care at a teaching hospital.
Ethnicity was associated with differences in presentation and outcome of patients with gastric adenocarcinoma. APIs had a more favorable outcome than patients of other ethnicities. Further studies should target underlying biologic and socioeconomic factors to explain these differences.
Cancer 06/2008; 113(3):461-9. · 4.77 Impact Factor
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Michelle M Kim, Paul F Mansfield,
Prajnan Das,
Nora A Janjan,
Brian D Badgwell,
Alexandria T Phan,
Marc E Delclos,
Dipen Maru,
Jaffer A Ajani,
Christopher H Crane,
Sunil Krishnan
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ABSTRACT: We retrospectively analyzed treatment outcomes among resectable gastric cancer patients treated preoperatively with chemoradiation therapy (CRT) but rendered ineligible for planned surgery because of clinical deterioration or development of overt metastatic disease.
Between 1996 and 2004, 39 patients with potentially resectable gastric cancer received preoperative CRT but failed to undergo surgery. At baseline clinical staging, 33 (85%) patients had T3-T4 disease, and 27 (69%) patients had nodal involvement. Most patients received 45 Gy of radiotherapy with concurrent 5-fluorouracil-based chemotherapy. Twenty-one patients underwent induction chemotherapy before CRT. Actuarial times to local control (LC), distant control (DC), and overall survival (OS) were calculated by the Kaplan-Meier method.
The cause for surgical ineligibility was development of metastatic disease (28 patients, 72%; predominantly peritoneal, 18 patients), poor performance status (5 patients, 13%), patient/physician preference (4 patients, 10%), and treatment-related death (2 patients, 5%). With a median follow-up of 8 months (range, 1-95 months), actuarial 1-year LC, DC, and OS were 46%, 12%, and 36%, respectively. Median LC and OS were 11.0 and 10.1 months, respectively.
Patients with potentially resectable gastric cancer treated with preoperative CRT are found to be ineligible for surgery principally because of peritoneal progression. Patients who are unable to undergo planned surgery have outcomes comparable to that of patients with advanced gastric cancer treated with chemotherapy alone. CRT provides durable LC for the majority of the remaining life of these patients.
International Journal of Radiation OncologyBiologyPhysics 06/2008; 71(1):167-72. · 4.11 Impact Factor
