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Multi-Institutional Trial of Preoperative Chemoradiotherapy in Patients With Potentially Resectable Gastric Carcinoma

From The University of Texas M.D. Anderson Cancer Center, Houston, TX; Washington University, St Louis, MO; and Mayo Clinic, Scottsdale, AZ

Address reprint requests to Jaffer A. Ajani, MD, Department of Gastrointestinal Medical Oncology, Stop 426, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030; e-mail: jajani{at}mdanderson.org

	ABSTRACT

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

 
PURPOSE: In the West, curative (R0) resection is achieved in approximately 50% of patients with localized gastric carcinoma, and more than 60% die of cancer following an R0 resection. A multi-institutional study of preoperative chemoradiotherapy was done to assess the R0 resection rate, pathologic complete response (pathCR) rate, safety, and survival in patients with resectable gastric carcinoma.

PATIENTS AND METHODS: Operable patients with localized gastric adenocarcinoma were eligible. Staging also included a laparoscopy and endoscopic ultrasonography (EUS). Patients received up to two 28-day cycles of induction chemotherapy of fluorouracil, leucovorin, and cisplatin, followed by 45 Gy of radiation plus concurrent fluorouracil. Patients were then staged and surgery was attempted.

RESULTS: Thirty-four patients were registered at three institutions. One ineligible patient was excluded. Most patients had a promixal cancer and EUST3N1 designation. Twenty-eight (85%) of 33 patients underwent surgery. The R0 resection rate was 70% and pathCR rate was 30%. A pathologic partial response (< 10% residual carcinoma in the primary) occurred in eight patients (24%). EUS T plus N and postsurgery T plus N correlation showed significant downstaging (P = < .01). The median survival time for 33 patients was 33.7 months. Patients achieving a pathCR or pathPR had a significantly longer median survival time (63.9 months) than those achieving less than pathPR (12.6 months; P = .03). There were two treatment-related deaths.

CONCLUSION: Our data suggest that the three-step strategy of preoperative induction chemotherapy followed by chemoradiotherapy resulted in substantial pathologic response that resulted in durable survival time. This strategy is worthy of a direct comparison with postoperative adjuvant chemoradiotherapy.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

 
Localized gastric carcinoma presents special strategic and practical challenges. An achievement of a curative (R0) resection (a potentially curative resection when the margins are free of cancer cells) and postoperative American Joint Committee on Cancer (AJCC) stage dictate the survival of patients. Patients with less than R0 resection have a worse survival time than those with an R0 resection.^1,2 Although the goal of each surgical attempt is to achieve an R0 resection, it is possible for fewer than 50% of patients.^3,4 In one study, an R0 resection rate was achieved in only 23% of 13,295 patients explored.³ This could have been due to inadequate staging. However, for the R0 group, a median survival time of 35 months and a 5-year survival rate of up to 40% can now be achieved in selected patients receiving postoperative adjuvant chemoradiotherapy.⁵ Postoperative AJCC stage in patients with localized gastric carcinoma is often II or higher,² and the overall survival time of patients correlates well with AJCC stage.^6-8

Understanding patterns of relapse after resection is paramount for designing therapeutic strategies. Clinical, reoperation, and autopsy series demonstrate a high incidence of locoregional and distant relapses after an R0 resection.^9-14 Local relapse was the only evidence of cancer in 29% of the 86 reoperation patients and as any component of relapse in 88%.¹² The locoregional relapse rate after an R0 resection in 3,044 patients was 41%.³ It is clear, however, that these outcomes in large series do not reflect the outcomes at large institutions familiar with multidisciplinary approaches to localized gastric carcinoma.

The strategy of preoperative therapy could potentially address the two important issues of poor R0 rates and the high rates of locoregional relapse. Theoretically, an effective preoperative approach can facilitate R0 resection and reduce local relapses.^15,16 It is also conceivable that the rate of pathologic complete response (pathCR) could be higher than 20% and provide substantial survival advantage. The role of preoperative chemoradiotherapy in reducing peritoneal dissemination during surgery is debatable, as is the value of induction chemotherapy in treating metastases early. The preoperative approach is better tolerated than the postoperative approach.^15,16 In our previous small pilot, preoperative chemoradiotherapy was feasible,¹⁷ and in another trial, preoperative radiotherapy, compared with surgery alone, resulted in reduction of local recurrence and prolonged survival time for pretreated gastric cancer patients.¹⁸

Nearly 33% of postoperative radiation fields had to be redesigned in the intergroup trial.⁵ In addition, surgeons are often not defining the potential radiation fields. These difficulties with postoperative approach make preoperative chemoradiotherapy approach relatively easy, because it forces a multimodality interaction before treatment, and the precise location and extent of carcinoma are much better understood in the preoperative setting than in the postoperative setting.

Our primary hypothesis was that preoperative chemoradiotherapy would result in a 20% rate of pathCR. Thus, the purpose of the study was to define the pathCR rate and toxicity in a limited multi-institutional setting. Adopting the three-step approach, we used chemotherapy defined by Leichman et al.¹⁹ It was followed by chemoradiotherapy and surgery.

	PATIENTS AND METHODS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

 
Patient Selection and Evaluation
All patients with localized histologically confirmed gastric adenocarcinoma were eligible. The bulk of cancer was in the stomach, even though the gastroesophageal junction (GEJ) may have been involved. Patients had chest radiograph, computed tomography (CT) of the abdomen (pelvis and chest if needed), upper gastrointestinal barium radiographs, an esophagogastro-duodenoscopy with endoscopic ultrasonograhy (EUS), ECG, SMA-12 (liver functions, renal functions, and other serum chemistries), electrolytes, CBC, and baseline carcinoembryonic antigen level. Patients with T2-3 with any N and T1N1 carcinoma were eligible. T-stage was defined only by EUS. All patients had a multidisciplinary evaluation. A laparoscopic staging and J-tube placement was performed in all patients. Nutritional counseling was provided as needed. All patients signed a written informed consent.

Patients with T4, M1, or T1N0 carcinoma were not eligible. Patients with ascites or gross peritoneal carcinoma were ineligible. Patients with uncontrolled medical conditions (eg, diabetes, hypertension, New York Heart Association class III or IV, or psychiatric illness) were not eligible, nor were patients who could not comprehend or comply with the study.

Study Design
The primary objective of the study was to observe a 20% pathCR rate. The secondary objective was to assess the toxicity (an early stopping rule was based on 10% treatment-related mortality). The second induction chemotherapy cycle was given in the absence of cancer progression. In case of local progression, the patient went on to receive concurrent chemoradiotherapy. Patients were taken off protocol if distant metastases occurred. Responses were judged using radiographic or endoscopic techniques. If a patient had an R0 resection, no further therapy was given; but in case of less than R0 resection (R1, positive margin; R2, gross carcinoma; or M1), palliative care was given.

Step 1: Chemotherapy
Chemotherapy consisted of continuous infusion fluorouracil (200 mg/m²/d) by a central venous access for 21 days, bolus leucovorin (20 mg/m²) on days 1, 8, and 15, and cisplatin 20 mg/m²/d on days 1 through 5. This chemotherapy was repeated on day 29 if there was recovery from side effects ( grade 1). Patients received standard hydration and antiemetics.

Using the National Cancer Institute Common Toxicity Criteria version 2.0, the drug doses were decreased by 25% (grade 3 nonhematologic or grade 4 hematologic toxicity). The doses were never increased. CBCs were done weekly. Serum chemistries were monitored before each course.

Step 2: Chemoradiotherapy
The interval between the first day of last chemotherapy and the first day of chemoradiotherapy was at least 28 days. Radiation fields included the entire stomach plus perigastric extension, if present, and draining lymph nodes (gastric, celiac, porta hepatis, gastroduodenal, splenic-suprapancreatic, and retropancreatico-duodenal). For lesions involving the cardia or GEJ, a 5-cm margin of esophagus was included, and for distal lesions at or near the gastroduodenal junction, a 5 cm margin of duodenum was recommended. Pretreatment diagnostic studies were used to determine the maximum extent of disease relative to both the primary tumor and nodal groups (esophagoscopy, barium swallow radiographs, CT on chest and abdomen). Idealized fields were modified, as needed, to shield at least two-thirds of one kidney. For proximal lesions, cardiac shielding was recommended, along with evaluation of lateral fields for a component of treatment.

Linear accelerators were used to deliver a dose of 45 Gy in 25 fractions of 1.8 Gy over 5 weeks, using either parallel opposed anterior-posterior–posterior-anterior fields or anterior-posterior–posterior-anterior plus paired laterals. The minimun energy allowed was 6 MV photons, with a preferred energy of 10 MV.

The concurrent outpatient fluorouracil was given at 300 mg/m²/d by continuous infusion by a portable pump 5 days each week (usually starting on a Monday and ending on Friday, after radiation).

Step 3: Surgery
The type of surgery depended on the location and extent of the primary. A luminal gastric margin of at least 5 cm was obtained when feasible. For distal cancers, a 2-cm duodenal margin was obtained when feasible, and frozen section confirmation of a negative margin was sought. For proximal cancers, a 3 cm esophageal margin was obtained, and frozen section confirmation of a negative margin was sought. For distal cancers, a subtotal gastrectomy was considered adequate, and total gastrectomy was at the discretion of the surgeon. For proximal cancers, either a total gastrectomy or esophagogastrectomy was permitted. En bloc resection of adjacent organ(s) was required when there was question of involvement of that organ. The spleen was preserved when feasible. An attempt was made to perform a D2 type nodal dissection, though omental bursectomy was not required. The left gastric artery was divided at its origin, and the hepatic, celiac, and proximal splenic nodes were removed. Clips were placed to mark areas of tumor adhesions for purpose of follow-up CT studies. During surgery, a J-tube was placed for temporary postoperative nutritional support.

Response, Toxicity Criteria, and Data Management
Upper gastrointestinal barium radiographs were done after each 28-day cycle of induction chemotherapy and just before surgery. Esophagogastroduodenoscopy, CT of the abdomen, chest radiography, and all blood tests were repeated before surgery.

Previously described criteria for response evaluation were refined.^16,17 A pathCR was defined as an absence of carcinoma cells in the primary site, and a pathologic complete response (pathPR) was defined as less than 10% of residual cancer cells in the stomach.

Follow-Up
Patients were assessed at 3, 6, and 12 months and then every 6 months until 5 years or death.

Statistical Methods
Our hypothesis was that the proposed strategy would result in a 20% pathCR rate. Simon's two-stage design was used. In the first stage, 21 patients were to be assessed; we expected that more than one pathCR would be observed. Then 22 additional patients were to be added. We estimated that 90% of registered patients would undergo surgery.

Patient responses (pathCR and pathCR + pathPR) were crosstabulated by sex, tumor location, and baseline stage. Baseline T-stage data were grouped into two categories: T1 or T2 (first category) or T3 (second category). Fisher's exact tests were used to assess the association between each of these factors and response rate. Survival time was defined as the time from start of treatment until death, if both of these time points were recorded. If a death date was not available, then the date of last follow-up was used in its place. Data from living patients were counted as censored. Log-rank tests were used to test for differences in survival distributions by sex, tumor location, baseline and postoperative T and N, and downstaging with respect to N stage or T stage. Univariate Cox proportional hazards models were fit, yielding estimates of hazard ratios for each of these factors. All statistical tests were two-sided and performed at a .05 significance level.

	RESULTS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

 
Thirty-four patients were registered. One patient (3%) withdrew consent after one cycle of induction chemotherapy, was lost to follow-up, and is considered not assessable. Characteristics of the 33 assessable patients are shown in Table 1.

All 33 patients were evaluated for toxicity, pathologic response, disease-free survival, and overall survival.

Response to Induction Chemotherapy.
Some degree of objective regression was noted in 16 patients(48%). There was no progression of the primary carcinoma in any patient. Symptomatic improvement, particularly relief of early satiety, was reported in 50% of patients. However, four patients developed M1 cancer before surgery (and five had unsuspected M1 cancer at surgery).

Response to Chemoradiotherapy
Further improvement in carcinoma was observed after chemoradiotherapy in additional 11 patients.

Surgical Findings and Surgical Pathology
Twenty-eight (85%) of the 33 patients underwent surgery. Five patients did not have surgery; one died after one cycle of induction chemotherapy, and four developed M1 carcinoma. An R0 resection was achieved in 23 (82% of 28 or 70% of 33) patients.

A pathCR was noted in 10 patients (36% of 28 undergoing surgery or 30% of 33 assessable patients). A pathPR was noted in 8 (29% of 28 undergoing surgery or 24% of 33 assessable patients). Thus the overall pathCR plus pathPR was noted in 64% of 28 undergoing surgery or 55% of 33 assessable patients. Five of the 28 patients were found to have M1 cancer at surgery. In 23 patients who underwent gastrectomy, the primary carcinoma was T3 in two patients (7% of 28 patients undergoing surgery), T0 in 10 (36% of 28 patients undergoing surgery), T2 in three patients (11%), and T1 in eight patients (29%). Similarly, there were no nodal metastases in 17 patients (61% of 28 undergoing surgery) and N1 in six patients (21%). The median number of examined nodes in the 23 resected specimens was 16 (range, 0 to 26 nodes); the median number of nodes with carcinoma was three (range, 0 to 13 nodes); and the median number of negative nodes was 13 (range, 0 to 26 nodes).

Correlation Between EUS stage and Pathologic Stage
A correlation between the pretreatment EUS and post-treatment pathologic stages in the 23 gastrectomy patients is shown in Table 2.

Survival
At a median follow-up of more than 50 months (minimum follow-up, 48 months; maximum follow-up, 84 months), 13 (39%) of the 33 patients remain alive. The median survival time for all 33 patients is 33.7 months, and the 2-year survival rate is 54% (Fig 1). Among the 20 patients who died, one died of chemotherapy-induced sepsis, and one patient died within 30 days of surgery. The remaining 18 patients died of carcinoma. We examined the effect of various factors on survival, including location, sex, evidence of T and N down staging, pretreatment EUS T and N stages, and the degree of pathologic response; among these, T-stage downstaging (P = .002), achievement of pathCR or pathPR (P = .03), and the type of pathologic response (pathCR > pathPR; P = .01) correlated significantly with overall survival (Table 4 and Fig 2).

View larger version (15K): [in this window] [in a new window]   Fig 1. Kaplan-Meier survival plot for all 33 patients. Median survival time, 33.7 months.

View larger version (13K): [in this window] [in a new window]   Fig 2. Kaplan-Meier survival plot according to type of pathologic response after surgery for 28 explored patients. Median survival time, 64 months for patients with pathologic complete response (CR) and 12.6 months for patients with pathologic partial response (PR).

View larger version (13K): [in this window] [in a new window]   Fig 3. Kaplan-Meier disease-free survival plot according to type of pathologic response after surgery for 28 explored patients. Median disease-free survival time, 46 months for patients with pathologic complete response (CR) and 5 months for patients with pathologic partial response (PR).

Chemotherapy-Induced Toxicity
One patient died of neutropenic sepsis as a result of the first cycle of induction chemotherapy. Hematologic and nonhematologic toxic effects following each cycle are shown in Table 5.

	DISCUSSION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

 
The strategy of preoperative therapy of locoregional gastric carcinoma is now a well-accepted research direction. In Europe, several phase III trials comparing preoperative chemotherapy to surgery alone are underway. Preliminary data of one trial of approximately 500 patients suggest that preoperative therapy (combined with postoperative chemotherapy) resulted in a statistically significant prolongation of progression-free survival in addition to improved R0 resection rate and some down-staging, compared with that from surgery alone.²⁰ Survival data on this and other trials will be forthcoming.

The differences in the patient populations and outcome expectations exist between preoperative and postoperative approaches. Postoperative adjuvant chemoradiotherapy is effective,⁵ but the preoperative approach is investigational. The goal of postoperative therapy is to reduce the rate of relapse and improve survival rates. The postoperative adjuvant therapy is appropriate for selected R0 patients with certain AJCC stage. More than 50% of patients with localized gastric carcinoma may not qualify for postoperative adjuvant chemoradiotherapy because of a low R0 resection rate in the West.

However, the pool of patients who would qualify for a preoperative strategy is much larger than it is for postoperative approach. The very essence of preoperative approach is to facilitate an R0 resection rate (an independent prognostic variable), but it also embraces all the other end points of postoperative adjuvant therapy. Interestingly, the median survival time (34 months) in our study was similar to that from preoperative chemoradiotherapy (35 months).⁵ The preoperative strategy cannot be executed without a multidisciplinary evaluation. Although the same is true for the postoperative setting, in reality it is often fragmented and disappointing.²¹ The diagnosis of gastric or GEJ carcinoma is often made by a gastroenterologist, and after a limited staging, the patient is operated on by a surgeon. In the retrospective reviews of patients entering Intergroup 116, it was suggested that the type of surgery performed was not optimal.^22,23 The operating surgeons were not anticipating that patients would participate in an adjuvant trial. Even today, many community physicians do not participate in a multidisciplinary approach.

Our data demonstrate that a good pathCR rate can be achieved in gastric carcinoma and is similar to that obtained in esophagus cancers.²⁴ Ninety-four percent of our patients had an EUS T3, and 65% had an EUS N1 carcinoma, and yet the pathCR rate was 30%. In addition, 24% had a pathPR. Unfortunately, clinical parameters cannot predict the level of pathologic response, but T-stage downstaging (EUS T v pathologic T), and pathCR or pathPR predict for an improved survival time. The median survival time of 18 patients who achieved a pathCR or pathPR was 63.9 months, compared with 10 patients who achieved less than pathPR (12.6 months; P = .03). The same parameters also reliably predicted for DFS. Except for one postoperative death, there were no undue surgical complications in our series. Positron emission tomography was not performed, because it was not available.

Peritoneal cavity remained a frequent failure site despite laparoscopic screening before protocol therapy. The target accrual was 43 patients, but the study was terminated after accrual of 34 patients because of funding problems. An observed pathCR rate of 30% in 33 patients met the primary end point, even if none of the remaining 10 hypothetical patients had a pathCR.

In conclusion, this is the first multi-institutional trial showing that a substantial pathCR plus pathPR rate is possible in localized gastric carcinoma patients treated with induction chemotherapy followed by preoperative chemoradiotherapy. PathCR and pathPR do translate into significant survival advantage. Even though further refinement of this strategy is necessary, this approach is worthy of a direct comparison with the postoperative adjuvant chemoradiotherapy.

	Authors' Disclosures of Potential Conflicts of Interest

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

 
The authors indicated no potential conflicts of interest.

	NOTES

 
Authors' disclosures of potential conflicts of interest are found at the end of this article.

	REFERENCES

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... REFERENCES

 
1. Bonenkamp JJ, Hermans J, Sasako M, van de Velde CJH: Extended lymph node dissection for gastric cancer. N Engl J Med 340:908–914, 1999[Abstract/Free Full Text]

2. Hundahl SA, Phillips JL, Menck HR: The National Cancer Data Base report on poor survival of US gastric carcinoma patients treated with gastrectomy. Cancer 88:921–932, 2000[CrossRef][Medline]

3. Wanebo HJ, Kennedy BJ, Chmiel J, et al: Cancer of the stomach: A patient care study by the American College of Surgeons. Ann Surg 218:583–592, 1993[Medline]

4. Adashek K, Sanger J, Longmire WP: Cancer of the stomach: Review of consecutive ten-year intervals. Ann Surg 198:6–10, 1979

5. Macdonald JS, Smalley S, Benedetti J, et al: Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345:725–730, 2001[Abstract/Free Full Text]

6. Hundahl SA, Menck HR, Mansour EG, Winchester DP: The National Cancer Data Base report on gastric carcinoma. Cancer 80:2333–2341, 1997[CrossRef][Medline]

7. Siewert JR, Bottcher K, Stein HJ, et al: Relevant prognostic factors in gastric cancer: Ten-year results of the German gastric cancer study. Ann Surg 228:449–461, 1998[CrossRef][Medline]

8. Kim JP, Lee JH, Kim SJ, et al: Clinicopathologic characteristics and prognostic factors in 10783 patients with gastric cancer. Gastric Cancer 1:125–133, 1998[CrossRef][Medline]

9. McNeer G, Vanderberg H, Donn F, et al: A critical evaluation of subtotal gastrectomy for the cure of cancer of the stomach. Ann Surg 134:1–7, 1951[CrossRef]

10. Thomson FB, Robins RE: Local recurrence following subtotal resection for gastric carcinoma. Surg Gynecol Obstet 95:341–344, 1952

11. Wisbeck WM, Becher EM, Russell AH: Adenocarcinoma of the stomach: Autopsy observations with therapeutic implications for the radiation oncologist. Radiother Oncol 7:13–18, 1986[Medline]

12. Gunderson LL, Sosin H: Adenocarcinoma of the stomach: Areas of failure in a reoperation series (second or symptomatic looks): Clinicopathologic correlation and implications for adjuvant therapy. Int J Radiat Oncol Biol Phys 8:1–11, 1982

13. Landry J, Tepper J, Wood W, et al: Analysis of survival and local control following surgery for gastric cancer. Int J Radiat Oncol Biol Phys 19:1357–1362, 1990[Medline]

14. Xiong HQ, Gunderson LL, Yao J, et al: Chemoradiation for resectable gastric cancer. Lancet Oncol 4:498–505, 2003[CrossRef][Medline]

15. Ajani JA, Mayer RJ, Ota DM, et al: Preoperative and postoperative chemotherapy for potentially resectable gastric carcinoma. J Natl Cancer Inst 85:1839–1844, 1993[Abstract/Free Full Text]

16. Ajani JA, Mansfield PF, Lynch PM, et al: Enhanced staging and all chemotherapy preoperatively in patients with potentially resectable gastric carcinoma. J Clin Oncol 17:2403–2411, 1999[Abstract/Free Full Text]

17. Lowy AM, Feig BW, Janjan N, et al: A pilot study of preoperative chemoradiotherapy for resectable gastric cancer. Ann Surg Oncol 8:519–524, 2001[CrossRef][Medline]

18. Zhang ZX, Gu XZ, Yin WB, et al: Randomized clinical trial combination on the preoperative irradiation and surgery in the treatment of adenocarcinoma of the gastric cardia (AGC): Report on 370 patients. Int J Radiat Oncol Biol Phys 42:929–934, 1998[CrossRef][Medline]

19. Leichman L, Silberman H, Leichman CG, et al: Preoperative systemic chemotherapy followed by adjuvant postoperative intraperitoneal therapy for gastric cancer: A University of Southern California pilot program. J Clin Oncol 10:1933–1942, 1992[Abstract]

20. Allum W, Cunningham D, Weeden S, et al: Perioperative chemotherapy in operable gastric and lower oesophageal cancer: A randomized, controlled trial (the MAGIC trial, ISRCTN 93793971). Proc Am Soc Clin Oncol 22:249, 2003 (abstr 998)

21. Ajani JA: Operate on my stomach cancer? Oh no, not you, or not yet. J Clin Oncol 22:1763–1764, 2004[Free Full Text]

22. Estes NC, Macdonald JS, Touijer K, et al: Inadequate documentation and resection for gastric cancer in the Untied States: A preliminary report. Am Surg 64:680–685, 1987

23. Hundahl SA, Macdonald JS, Benedetti J, et al: Surgical treatment variation in a porspective, randomiized trial of chemoradiotherapy in gastric cancer: The effect of undertreatment. Ann Surg Oncol 9:278–286, 2002[CrossRef][Medline]

24. Gibson MK, Forastiere AA: Combined-modality therapy for esphogeal cancer: Are we making progress? Cancer J 9:238–239, 2003[Medline]

Submitted January 6, 2004; accepted April 16, 2004.

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