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Keywords:

  • diffuse type;
  • gastric cancer;
  • adjuvant radiotherapy;
  • Surveillance, Epidemiology, and End Results (SEER);
  • survival

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SUPPORT
  8. CONFLICT OF INTEREST DISCLOSURES
  9. REFERENCES

BACKGROUND

Diffuse-type gastric cancer is observed in approximately one-third of gastric cancers, yet the optimal treatment remains controversial. In the recently published Intergroup 0116 trial, a subgroup analysis demonstrated a lack of a long-term survival benefit for adjuvant chemoradiation therapy among patients with diffuse-type gastric cancer.

METHODS

The Surveillance, Epidemiology, and End Results registry database was queried for patients who were newly diagnosed with diffuse-type gastric cancer between 2002 and 2005 and underwent surgical resection with or without adjuvant radiotherapy (RT). Overall survival (OS) was analyzed by the Kaplan-Meier method. Cox proportional hazards models were used to investigate the association between adjuvant RT and OS, with and without adjusting for other factors. In addition, propensity score methods were used to control for the possible effects of measured confounders.

RESULTS

A total of 1889 cases of surgically resected diffuse-type gastric cancer were included in the analysis; of these cases, 782 patients received adjuvant RT and 1107 did not receive RT. The median survival time was 30 months in the group treated with adjuvant RT versus 18 months in the group that did not receive RT with matched propensity scores (P<.001). The Cox model confirmed the improvement in OS in patients who received adjuvant RT (hazard ratio, 0.75; 95% confidence interval, 0.65-0.82 [P<.001]).

CONCLUSIONS

The current population-based observational study suggested a potential survival benefit for adjuvant RT among patients with diffuse-type gastric cancer. The standard treatment will likely remain controversial until evidence becomes available from phase 3 randomized trials exclusively for patients with diffuse-type gastric cancer. Cancer 2014;120:3562–3568. © 2014 American Cancer Society.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SUPPORT
  8. CONFLICT OF INTEREST DISCLOSURES
  9. REFERENCES

Gastric carcinoma ranks as the 13th most commonly diagnosed cancer, with approximately 11,000 patients expected to die of the disease in the United States in 2014.[1] Microscopically, gastric cancer can be divided into 2 main histological categories, intestinal type and diffuse type, according to the classification scheme originally described by Lauren in 1965.[2] Intestinal-type tumor cells are said to form irregular glandular structures and are frequently associated with intestinal metaplasia and atrophic gastritis in the adjacent mucosa, whereas diffuse histology is characterized by a poorly cohesive cellular pattern with little or no gland formation. In many instances, the majority of tumor cells of diffuse histology secrete copious mucus, which may accumulate in the intracellular compartment and push the nucleus to the periphery of the cell, giving rise to the term of signet ring cell carcinoma.[2] Another morphologic variant of diffuse-type gastric cancer is linitis plastica (“leather bottle”), which is characterized by diffuse tumor cell infiltration into the stomach wall accompanied by extensive fibrosis.

Clinically, diffuse-type gastric cancer is distinguished from intestinal-type disease by several characteristics, including relatively younger patients, a higher prevalence of lymph node invasion, and lower R0 surgical resection rates. The optimal treatment for patients with diffuse-type gastric cancer has remained largely undefined because to our knowledge no trials to date have been dedicated to the study of this histology despite findings that the incidence of diffuse-type gastric carcinoma has been increasing and currently comprises 25% to 45% of gastric cancer cases in Western countries.[3-8] Recently, a French multicenter retrospective study of approximately 1000 patients with signet ring cell carcinoma demonstrated worse survival associated with perioperative chemotherapy compared with adjuvant chemotherapy.[9] This finding is of particular importance given that the perioperative chemotherapy approach has been increasingly adopted for either intestinal-type or diffuse-type advanced gastric cancer in Europe.[10] In North America, in which D2 lymph node dissection is not commonly performed, adjuvant chemotherapy combined with radiotherapy (RT) has been recommended as a standard option for patients with gastric cancer of stage IB or higher since the publication of the Intergroup (INT)−0116 trial in 2001.[11] However, the efficacy of adjuvant chemoradiation for diffuse-type gastric cancer has recently been put into question by the updated INT-0116 results, which demonstrated a lack of long-term survival benefit for women and for those with diffuse histology in an unplanned and likely underpowered subgroup analysis.[12]

In the current study, we used the Surveillance, Epidemiology, and End Results (SEER) database, which covers up to 25% of the patient population in the United States, to examine whether the findings of the updated INT-0116 subgroup analysis are consistent with outcomes from a large population sample.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SUPPORT
  8. CONFLICT OF INTEREST DISCLOSURES
  9. REFERENCES

Case Inclusions and Exclusions

The SEER, a population-based reporting system, was surveyed for the retrospective collection of data used in the analysis. The SEER program collects and publishes cancer incidence and survival data from 18 population-based cancer registries, covering >25% of the US population. Because no personal identifying information was used in the analysis, this study was granted an exemption from the Institutional Review Board of the study institution on March 30, 2012.

The SEER database from January 1, 2002 to December 31, 2005 was queried. We selected this range because the INT-0116 trial using adjuvant chemoradiation was published in 2002, and the results of the next landmark gastric cancer trial (MAGIC trial) using perioperative chemotherapy were published in 2006.[10, 11] The analysis was limited to the cohort of patients with newly diagnosed diffuse-type gastric cancer (International Classification of Diseases for Oncology, 3rd Edition [ICD-03] histology codes:8145/3 [carcinoma diffuse type], 8490/3 [signet ring cell carcinoma], and 8142/3 [linitis plastica]) who underwent surgical resection with or without adjuvant RT. Examined covariates included patient demographics (age at presentation, sex, and race), tumor location (fundus, cardia, body, lesser curvature, greater curvature, antrum, pylorus, and overlapping lesion/not otherwise specified [NOS]), tumor grade, histological subtype (diffuse-type carcinoma, signet ring cell carcinoma, and linitis plastica), extent of surgical resection (subtotal or total), number of lymph nodes assessed, and American Joint Committee on Cancer (AJCC) stage of disease. For the purpose of analysis, overlapping tumor location or location NOS were combined and labeled as “overlapping/NOS.” The following cases were excluded from analysis of the data: multiple primary malignancies (78 cases), unknown race (36 cases), unspecified tumor location (278 cases), unknown tumor grade (303 cases), unknown number of lymph nodes assessed (52 cases), unknown AJCC stage (467 cases), surgery limited to excisional biopsy/palliative procedure or surgery type unknown (1956 cases), and preoperative RT or unknown radiation sequence with surgery (141 cases). Cases with AJCC stage IA disease (412 cases) and stage IV disease with M1 (423 cases) were excluded so that cases within the study cohort met basic criteria for enrollment in the INT-0116 trial. In addition, we excluded patients who survived <3 months, <6 months, or <9 months after surgery to account for immortal time bias in sensitivity analyses. Given the consistent outcomes, a landmark of 6 months after surgery was selected and 405 patients who survived <6 months were excluded.

Treatment

Information regarding the first course of treatment (given within 4 months after diagnosis) included surgery and RT. Subtotal gastrectomy included antrectomy, partial upper gastrectomy, partial lower gastrectomy, and partial gastrectomy NOS. Total gastrectomy included total gastrectomy and gastrectomy with organs. According to the SEER data dictionary, RT was defined as external-beam RT using gamma rays generated from a cobolt-60 source or high-energy photons generated from a linear accelerator.

Statistical Analysis

Patient demographics and tumor characteristics between the 2 groups (those treated without RT vs those who received adjuvant RT) were compared using chi-square tests for categorical variables and 2-sample Student t tests for continuous variables. The Kaplan-Meier method was used to estimate overall survival (OS) rates among patients in the 2 treatment groups and log-rank tests were conducted to examine whether the difference in survival between the 2 groups was statistically significant. To investigate the potential association between treatment (no RT or adjuvant RT) and survival outcomes, we used Cox proportional hazards regression models, adjusting for other factors. All variables were included in the proportional hazards regression models except N classification given that the grouped AJCC stage includes N classification. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated for OS, using both unadjusted and adjusted Cox proportional hazards models.

In addition, we used propensity score analysis to balance measurable confounders between the group treated without RT and the group that received adjuvant RT. The probability that each patient would receive adjuvant RT was estimated using logistic regression models, which included age, race, number of lymph nodes assessed, N classification, and AJCC stage of disease. The resultant propensity scores were adjusted for in the Cox proportional hazards regression models to compare survival between patients treated without RT and those treated with adjuvant RT. The Cox proportional hazards regression analysis was subsequently conducted within each propensity score quintile. Alternatively, propensity score 1:1 matching using a greedy algorithm was used to pair each patient in the adjuvant RT group with 1 patient in the group that did not receive RT, whose propensity score was within the designated caliper size. The matched cohort was subsequently used for OS analysis with the Kaplan-Meier method. Statistical analyses were performed using Stata statistical software (StataCorp, College Park, Tex). All statistical tests were 2-sided and a P value of <.05 was considered statistically significant.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SUPPORT
  8. CONFLICT OF INTEREST DISCLOSURES
  9. REFERENCES

Patient Demographics and Tumor Characteristics

Between 2002 and 2005, a total of 1889 cases were identified from the SEER database. Overall, 782 patients received adjuvant RT and 1107 did not receive RT. Summary statistics are reported in Table 1. Compared with those patients who did not receive RT, patients in the group treated with adjuvant RT were younger and were more likely to have ≥15 lymph nodes dissected, N3 lymph node status, and higher AJCC stage of disease. To control for possible selection bias, we created a propensity score for the likelihood of receiving adjuvant RT based on age, race, number of lymph nodes assessed, N classification, and AJCC stage of disease. After adjustment with the propensity scores, all the variables except age and stage III/IV (M0) disease were found to be balanced among patients treated with adjuvant RT and without RT (P >.05) (Table 1).

Table 1. Demographics and Tumor Characteristics of Patients With Diffuse-Type Gastric Cancer by Treatment Received
 Adjuvant RTNo RT No RT (PS Matching) 
CharacteristicsNo.(%)No.(%)PaNo.(%)P (PS Matching)a
  1. Abbreviations: AJCC, American Joint Committee on Cancer; LNs, lymph nodes; NOS, not otherwise specified; PS, propensity score; RT, radiotherapy; SD, standard deviation.

  2. a

    Bold type indicates statistical significance (P <.05).

Age, y    <.001  <.001
Median (SD)58.0(13.1)63.5(14.4) 60.8(14.6) 
<4574(9.5)84(7.6) 67(8.6) 
45-59348(44.5)361(32.6) 310(39.6) 
60-74284(36.3)500(45.2) 329(42.1) 
≥7576(9.7)162(14.6) 76(9.7) 
Sex        
Male409(52.3)563(50.9).60412(52.7).88
Female373(47.7)544(49.1).60370(47.3).88
Race        
White481(61.5)752(67.9).003503(64.3).25
African American103(13.2)120(10.9).1496(12.4).65
Other198(25.3)235(21.1).03183(23.3).35
Tumor location        
Cardia97(12.4)139(12.6).94105(13.4).56
Fundus28(3.6)32(2.9).4122(2.8).39
Body86(11.0)134(12.1).4698(12.5).35
Antrum262(33.5)355(32.1).55247(31.6).45
Pylorus38(4.9)46(4.2).5333(4.2).54
Less curvature118(15.1)160(14.5).70119(15.2).94
Greater curvature45(5.8)72(6.5).5046(5.9).91
Overlapping/NOS108(13.7)167(15.1).44112(14.3).77
Tumor grade        
1-224(3.4)34(3.4).6624(3.1)1.00
3-4758(96.9)1073(96.6).66758(96.9)1.00
Histology        
Diffuse type146(18.7)209(18.9).91146(18.7)1.00
Signet ring cell596(76.2)858(77.5).51606(77.5).55
Linitis plastica40(5.1)40(3.6).1230(3.8).22
No. of LNs assessed        
<15420(53.7)649(58.6).03424(54.2).43
≥15362(46.3)458(41.4).03358(45.8).43
N classification        
N0343(43.8)488(44.0).07338(43.2).07
N1184(23.5)205(18.5).01166(21.2).28
N2141(18.0)181(16.4).34145(18.5).79
N3114(14.6)233(21.1)<.001133(17.0).19
AJCC stage        
IB98(12.5)182(16.4).02116(14.8).19
II186(23.8)200(18.1).003180(23.0).72
IIIA230(29.4)183(16.5)<.001180(23.0).004
IIIB93(11.9)77(7.0)<.00177(9.8).02
IV (M0)175(22.4)465(42.0)<.001229(29.3).002
Surgery        
Total289(37.0)397(35.9).63285(36.4).83
Subtotal493(63.0)710(64.1).63497(63.6).83
Total782 1107  782  

Survival Analysis

Figure 1 shows the OS curves of patients who did and did not receive RT. The median survival time was 30 months and the 3-year OS rate was 44% in the group treated with adjuvant RT, in contrast to the median survival of 18 months and 3-year OS rate of 31% for those with a matched propensity score in the group that did not receive RT (P <.001). Multivariate Cox proportional hazards regression analysis demonstrated that the addition of adjuvant RT was associated with better survival, with a HR of 0.75 (95% CI, 0.65-0.82; P <.001) (Table 2).

image

Figure 1. Kaplan-Meier survival curves are shown demonstrating a comparison of overall survival between patients treated with adjuvant radiotherapy (RT) and those who did not receive RT, with and without propensity score matching.

Download figure to PowerPoint

Table 2. Multivariate Analysis of Patients With Diffuse-Type Gastric Cancer
 Diffuse Typea 
VariableHR95% CIP
  1. Abbreviations: 95% CI, 95% confidence interval; AJCC, American Joint Committee on Cancer; HR, hazard ratio; LNs, lymph nodes.

  2. a

    Bold type indicates statistical significance (P <.05).

Radiotherapy 
Yes0.750.65-0.82<.001
NoneReferent  
Age1.021.01-1.02<.001
Race   
WhiteReferent  
African American0.910.74-1.12.38
Other0.780.67-0.92<.01
No. of LNs assessed   
<15Referent  
≥150.760.65-0.82<.001
AJCC stage   
IBReferent  
II2.611.74-3.51<.001
IIIA4.913.40-6.97<.001
IIIB4.863.22-7.41<.001
IV (M0)9.026.24-12.78<.001
Surgery   
TotalReferent  
Subtotal0.840.74-0.97.02

In keeping with the findings reported above, the Cox analysis adjusted for propensity score also showed similar results (Table 3). Furthermore, when data were analyzed separately within each propensity score quintile, there was a statistically significant association found between adjuvant RT and better survival within any of the strata, with a P value of .02 for the middle stratum (Table 3). By design, patients in the middle stratum had near-random propensity scores centered at 0.5 and represent the subgroup with the greatest adjustment for bias.

Table 3. Propensity Score Analysis: Risks of Death for Patients Treated With Adjuvant RT According to Propensity Score Quintile
 Overall Survival 
QuintileaHR95% CIPb
  1. Abbreviations: 95% CI, 95% confidence interval; HR, hazard ratio; RT, radiotherapy.

  2. a

    Quintiles represent patients grouped on the basis of the propensity score.

  3. b

    Bold type indicates statistical significance (P <.05).

  4. c

    The HR for the entire sample was adjusted for the propensity score.

Entire samplec0.710.60-0.78<.01
1 (lowest probability of adjuvant RT)0.830.68-0.94.04
20.800.70-0.78.02
30.720.62-0.81.02
40.700.61-0.79.03
5 (highest probability of adjuvant RT)0.660.44-0.89<.01

When each of the 3 diffuse histology subtypes was studied individually, there was a significant survival benefit found for adjuvant RT for all 3 subtypes: signet ring cell carcinoma (HR, 0.71; P<.01), diffuse-type carcinoma (HR, 0.89; P<.01), and linitis plastica (HR, 0.55; P<.001).

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SUPPORT
  8. CONFLICT OF INTEREST DISCLOSURES
  9. REFERENCES

Using a large population sample, the results of the current study demonstrated a significant survival benefit associated with adjuvant RT in patients with diffuse-type gastric cancer. Although the reason for this is a subject for speculation, the associated survival benefit could be attributed to the unfavorable locoregional control specific to diffuse-type gastric cancer. One of the poor prognostic factors among these patients is the higher prevalence of lymph node invasion found in diffuse-type gastric cancer,[7, 13] supported by the finding of lymph node involvement in >55% of the patients in the current study. In an analysis of lymph node-positive patients who underwent D2 lymph node dissection followed by adjuvant chemotherapy, the Korean ARTIST trial recently demonstrated a prolonged disease-free survival with the addition of adjuvant RT.[14] In light of the finding of diffuse-type histology in approximately 60% of all patients in the ARTIST trial, a potential benefit for adjuvant RT could be proposed for patients with diffuse-type gastric cancer with positive lymph nodes. Another poor prognostic feature of diffuse-type gastric cancer is a lower R0 surgical resection rate despite more extensive surgery, most likely due to the infiltrating characteristic that leads to more positive vertical resection margins.[7, 13, 15] Compared with surgeries performed in large tertiary centers, the percentage of suboptimal surgeries may be even greater in community hospitals, which have contributed approximately 50% of the gastrectomy cases to the SEER database.[16] It is not inconceivable that adjuvant RT may provide a locoregional control benefit and, ultimately, survival benefit in those patients who undergo suboptimal surgery or surgical resections with positive margins.

Several reasons may be proposed for the discrepancy between the results of the current study and those from the subgroup analysis of the updated INT-0116 trial. First, the patient population or treatment received could be different. The patients in the INT-0116 trial likely came from select academic centers and the treatments may not be reflective of those in the community setting. Although the prevalence of lymph node invasion in patients with diffuse-type histology was not specified in INT-0116 trial and therefore could not be compared with that in the SEER study, the percentage of R0 resections in the SEER database is likely greater than that noted in the INT-0016 study because approximately one-half of the gastrectomy cases included in the SEER database came from community hospitals, in which experience in oncologic gastrectomy may be inadequate.[16] However, direct evidence is largely lacking given that SEER did not collect information regarding gastrectomy surgical margin status, one of the important indicators of optimal surgery. Second, although most clinical trials require central pathology review by highly specialized pathologists, it could be speculated that the lack of a central pathology review in SEER may have resulted in a greater variability in interpretations of diffuse-type histology or signet ring carcinoma, defined as the presence of at least 50% of signet ring cells in the pathologic specimen.[17] One study from Stanford University showed a concordance rate of 77% between different pathologists regarding Lauren histology classification.[18] Therefore, the diffuse-type histology in SEER registry data may have included a small portion of intestinal-type histology for which adjuvant RT has been shown to confer a significant long-term survival benefit.[12] If this is the case, the current study may have overestimated the benefit of adjuvant RT among patients with diffuse-type gastric cancer. Conversely, it is likely that such commingling of diagnoses also occurs frequently in the community hospitals that contribute the majority of gastrectomy cases to the SEER database and our result is likely to be more generalizable.

In addition to the limitations in pathology review as discussed earlier, readers are advised to note the following limitations related to cancer registry databases. First, the current analysis of the nonrandomized patient population could not exclude the possibility of selection bias, in which patients with older age, more advanced stage of disease, and poor performance status were more likely forgo adjuvant treatment. The current study used propensity score analysis to balance possible measurable confounders. However, there were residual imbalances with regard to age and AJCC stage III/IV (M0) distribution between the group treated with adjuvant RT and the propensity score-matched group treated without RT. When the small yet statistically significant imbalances were further adjusted for in the Cox regression analysis, the survival benefits associated with adjuvant RT remained significant. In addition, we sought to mitigate the impact of performance status selection bias by censoring the current study data to include only those patients who survived >6 months postoperatively. In performing this sensitivity analysis, our aim was to eliminate some of those patients who did not receive adjuvant RT because of either poor overall condition after surgery or death occurring before they were considered for adjuvant treatment. Despite the possible selection bias due to age, cancer stage, and performance status, the OS in the current study was in keeping with that in the INT-0116 trial, suggesting a limited impact of the selection bias on clinical outcome. For example, in the current study, patients in the gastrectomy-alone group and those in the adjuvant therapy group had 3-year OS rates of 31% and 45%, respectively, whereas the INT-0016 subgroup analysis of patients with diffuse-type histology demonstrated 3-year OS rates of 33% and 41%, respectively.[12]

Second, there is missing information in the SEER database regarding the intent of RT. Although speculative, it is plausible that RT was delivered with a curative intent given the exclusion of patients with metastatic disease in the current study. In addition, the current study cohort demonstrated that approximately 40% of the eligible patients with diffuse-type gastric cancer (782 of 1889 patients) actually received adjuvant RT. Although the omission may point to a possible selection bias in the current study sample, it may also reflect differences in patterns of care in the community. This speculation was supported by our previous finding that only 45% of patients with nonmetastatic gastric cancer, either of the intestinal or diffuse type, received adjuvant RT when we used the SEER data from 2002 to 2005 to examine the use of the INT-0116 treatment scheme since its publication.[19] The relatively low percentage of adjuvant RT cases in the current study sample may also be partly attributable to the previously reported shortcomings in SEER coding, specifically the failure to record adjuvant RT in some of the patients. Several studies have demonstrated underreporting or underascertainment of RT administration in approximately 15% to 30% of patients with breast cancer in the SEER database.[20] In a similar vein, the group treated without RT in the current SEER study may have included some patients who actually received adjuvant RT. If this is the case, the results of the current study may have actually underestimated the survival benefit of adjuvant RT for patients with diffuse-type gastric cancer, because the OS rates in the group treated without RT would be improved by the inadvertent inclusion of patients who may have received adjuvant RT.

In addition, there is missing information in the SEER database regarding the use of chemotherapy, resulting in a potentially significant confounder in the current study. It is possible that patients may have received adjuvant chemotherapy or perioperative chemotherapy, although our cohort was limited to those treated between 2002 and 2005 (ie, before the adoption of the perioperative chemotherapy approach as used in the MAGIC trial published in 2006).[10] Although the MAGIC trial did not perform a subgroup analysis of patients with diffuse-type histology, the survival results from all patients included in the MAGIC trial were similar to those found in the current SEER study. The 5-year OS rate was 23% in the MAGIC trial versus 25% in the current study among patients who did not receive RT, and 36% versus 32%, respectively, in patients who received adjuvant RT.[10] Although perioperative chemotherapy has been the European standard of care for patients with advanced gastric cancer since the publication of the MAGIC trial,[10] several recent studies suggested unfavorable results when this approach was used in patients with diffuse-type gastric cancer. To our knowledge, the largest study to date was a French multicenter retrospective analysis of approximately 1000 patients with signet ring cell carcinoma.[9] It demonstrated worse survival and more extended surgery associated with perioperative chemotherapy than with adjuvant chemotherapy. The findings of low rates of downstaging and high rates of disease progression during the preoperative chemotherapy period suggested inherent chemoresistance in signet ring cell carcinoma and a deleterious effect of delaying definitive surgery for the ineffective preoperative chemotherapy.

Although the results from the current observational study have drawbacks and should be interpreted with caution, the results from the INT-0116 trial subset analysis are also limited. In our opinion, further phase 3 randomized trials designed exclusively for diffuse-type gastric cancer are necessary to provide high-level evidence regarding the optimal treatment. Multiple centers in France have participated in a phase 3 randomized trial evaluating a strategy of primary surgery followed by adjuvant chemotherapy versus perioperative chemotherapy for patients with resectable gastric signet ring cell carcinomas.[21] In Korea, a phase 3 trial (ARTIST II) subsequent to the published ARTIST trial currently is underway to enroll 1000 patients with gastric cancer with positive lymph nodes to evaluate the role of adjuvant RT in the setting of D2 gastrectomy followed by adjuvant chemotherapy.[14] Although the ARTIST II trial is not designed to analyze either intestinal-type or diffuse-type histology, it may provide sufficient power for a subgroup analysis regarding the role of adjuvant RT for diffuse-type gastric cancer if the ARTIST II trial were to include patients with diffuse-type gastric cancer in >50% of the accrual as the original ARTIST trial did.

The current large, population-based study suggests a potential benefit of adjuvant RT for patients with diffuse-type gastric cancer. The optimal treatment will likely remain controversial until high-level evidence becomes available from phase 3 randomized trials designed exclusively for diffuse-type gastric cancer, and a standard practice becomes widely adopted within the community.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SUPPORT
  8. CONFLICT OF INTEREST DISCLOSURES
  9. REFERENCES
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