Добавил:

Sekretar kiopkiopkiop18@yandex.ru t.me/Prokururor I Вовсе не секретарь, но почту проверяю Опубликованный материал нарушает ваши авторские права? Сообщите нам.

Вуз:

Ростовский Государственный Медицинский Университет

Предмет:

Медицина общая

Файл:

@xirurgi_2025 - 598 - файл

.pdf

Скачиваний:

Добавлен:

29.08.2026

Размер:

22 Мб

Скачать

☆

<<< < Предыдущая 11 12 13 14 15 16 17 18 19 20 21 2223 / 5023 24 25 26 27 28 29 30 31 32 33 34 35 > Следующая >>>

206

https://t.me/medicina_free

these studies are severely limited by the power to test for the interaction between dMMR status and chemotherapy effect. Several studies have also looked at other molecular mutations in the BRAF and KRAS genes including interactions of these factors with dMMR status as well as those with CpG Island methylator phenotype [18, 19, 25, 26]. No clear consensus has emerged with one study suggesting a BRAF mutation is prognostic for poorer overall survival in all stage II patients [18] and another in only those with pMMR status [25]. An additional study suggested a poorer survival for KRAS mutant tumors but not BRAF [19]. In none of the studies were KRAS, BRAF, or CIMP predictive of benet from chemotherapy and as such have not found their way into our treatment algorithms.

G. Dosunmu and C.-Y. Liao

Risk-Stratification: ctDNA andMinimal Residual Disease

Circulating tumor DNA (ctDNA) are DNA fragments that are released by neoplastic cells [29]. Its positivity after curative surgery provides evidence of micrometastases and minimal residual disease. It offers to be a promising noninvasive tool for personalizing treatment and deciding which patients will receive adjuvant chemotherapy, and which regimen to use.

A phase II study evaluated whether ctDNA guided approach could reduce the use of adjuvant therapy while reducing the risk of recurrence. This study enrolled patients based on either ctDNA or clinicopathologic features. ctDNA-negative patients were not treated. 15% in ctDNA guided group received chemotherapy compared to 28% in the standard management group. The primary endpoint, recurrencefree survival (RFS) at 2years, was non-inferior to the standard group (93.5% vs

92.4%; 95% CI: 1.25–2.65%). At 3years, RFS was 91.7% vs. 92.4%. Essentially, fewer patients received chemotherapy when the ctDNA-based approach was employed without sacricing the risk of recurrence, suggesting that potential role of ctDNA in guiding adjuvant therapy decisions [30]. While this study offered prognostic information, it did not provide evidence about the effect of chemotherapy treatment, and larger validation studies are needed. A major limitation of ctDNA is its sensitivity which can range from 50 to 60% [31], especially in early-stage tumors with few DNA fragments [29].

The CIRCULATE-US study (NCT05174169) is a prospective study to evaluate the role of ctDNA to guide adjuvant therapy decisions in high-risk stage II and III colon cancer. This phase II/III clinical trial stratied patients with resected colon cancer based on their ctDNA status, and randomized them to different adjuvant therapy regimens, with the primary objective of measuring DFS (Fig.17.1). Patients with negative baseline ctDNA (cohort A) will get randomized to receive adjuvant FOLFOX/CAPOX, or no adjuvant chemotherapy. Patients with baseline positive ctDNA (cohort B) will get randomized to receive adjuvant FOLFOX/CAPOX or FOLFOXIRI.Both cohorts will involve serial ctDNA monitoring. Patients from cohort A with detectable ctDNA at any point will be switched to cohort B. The CIRCULATE-US study will hopefully better enlighten practitioners on the potential use of ctDNA as a monitoring, prognostic, and treatment decision tool. If

17 Stage II Colon Cancer: Towards anIndividualized Treatment Approach

https://t.me/medicina_free

Patients with resected colon cancer

ctDNA test

207

ctDNA negative

(Cohort A)

CAPOX or

FOLFOX

Fig. 17.1 Circulate-US study (NCT05174169)

monitoring

ctDNA negative ctDNA positive

ctDNA positive

CAPOX or

FOLFOX

(Cohort B)

FOLFOXIRISerial ctDNA

successful, the trial may lead to the development of new treatment paradigms for stage II colon cancer, including MRD-directed adjuvant therapy.

Duration ofAdjuvant Therapy

The International Duration Evaluation of Adjuvant Chemotherapy (IDEA) was a collaboration of four to six phase III studies involving 3273 high-risk stage II colon cancer patients, that attempted to answer the question of the optimal duration of adjuvant chemotherapy in stage II colorectal cancer. Patients were randomly assigned to receive 3months vs. 6 months of adjuvant chemotherapy. Adjuvant therapy regimen was up to investigator discretion, and included FOLFOX (5- uorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin). The primary endpoint was 5-year disease-free survival. In the overall population, noninferiority was not demonstrated for 3 months of adjuvant therapy vs. 6months of adjuvant therapy (DFS 80.7% vs 83.9%, HR, 1.17; 80% CI, 1.05 to

1.31; P [for noninferiority] .39). However, preplanned subgroup comparisons showed a statistically signicant difference in patients receiving CAPOX vs. FOLFOX regimens. The 5-year DFS of 3months adjuvant CAPOX vs 6months was 81.7 vs 82%. (HR 1.02; 95% CI, 0.82 to 1.27) with fewer grade 3–5 toxicities in the 3months cohort. The 5-year DFS was higher with 6months of FOLFOX compared to 3months of FOLFOX (79.2% vs 86.5%, HR 1.41; 95% CI, 1.08 to

1.84), though 6months of FOLFOX was associated with more toxicities. Essentially, 3months of FOLFOX was inferior to 6months of FOLFOX, while 3 months of CAPOX was comparable to 6months of CAPOX with a HR closer to 1. This suggests a potential use of 3months of CAPOX in high-risk stage II patients, especially when taking into consideration the cost and toxicity prole. 6months of FOLFOX was superior to 3months of FOLFOX but had more toxicities [32]. A limitation of the IDEA study was that OS was not yet evaluated due to the short follow-up; longer

208

https://t.me/medicina_free

G. Dosunmu and C.-Y. Liao

follow-up is needed to fully evaluate the long-term outcomes of patients receiving 3months of CAPOX.The sample size was also not sufciently large to accurately detect small differences in DFS.

Overall, 3months CAPOX or 6months single-agent 5FU can be considered in high-risk stage II colon cancer patients taking into account the patient’s specic risk prole, comorbidities, side effects, and preferences. We reserve 6-months of oxaliplatin based adjuvant therapy for patients with multiple high-risk features.

Recommendations Based ontheData

1. All stage II colon cancer patients should be tested for dMMR either by IHC or

PCR and those with dMMR should not receive chemotherapy (evidence quality high, strong recommendation).

2. Patients with T4 tumors, high grade (pMMR), <12 LN sampled, or with perfora-

tion should receive adjuvant chemotherapy (evidence quality moderate, moderate recommendation).

3. Adjuvant therapy with 3months CAPOX or 6months single-agent 5FU can be

considered in high-risk stage II colon cancer patients taking into account the patient’s specic risk prole, comorbidities, side effects, and preferences. Patients with multiple high-risk features may be considered for 6-months of oxaliplatin-based adjuvant therapy (evidence quality moderate, moderate recommendation).

4. Patients with T4b tumors should receive oxaliplatin-based adjuvant therapy (evi-

dence quality weak, moderate recommendation).

5. ctDNA should be considered for surveillance and risk-stratication, and studies

are underway to investigate its role in guiding adjuvant therapy regimen. (evidence quality moderate, moderate recommendation).

References

1. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, editors. AJCC cancer staging manual. 7th ed. NewYork: Springer; 2010.

2. Quasar Collaborative G, Gray R, Barnwell J, McConkey C, Hills RK, Williams NS, etal. Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study. Lancet. 2007;370(9604):2020–9. https://doi.org/10.1016/S0140- 6736(07)61866- 2.

3. Figueredo A, Coombes ME, Mukherjee S. Adjuvant therapy for completely resected stage II colon cancer. Cochrane Database Syst Rev. 2008;2010(3):CD005390. https://doi.

org/10.1002/14651858.CD005390.pub2.

4. Erlichman C.Efcacy of adjuvant uorouracil and folinic acid in B2 colon cancer. International multicentre pooled analysis of B2 colon cancer trials (IMPACT B2) investigators. J Clin Oncol Off J Am Soc Clin Oncol. 1999;17(5):1356–63.

5. Andre T, Boni C, Navarro M, Tabernero J, Hickish T, Topham C, etal. Improved overall survival with oxaliplatin, uorouracil, and leucovorin as adjuvant treatment in stage II or III colon

17 Stage II Colon Cancer: Towards anIndividualized Treatment Approach

https://t.me/medicina_free

cancer in the MOSAIC trial. J Clin Oncol Off J Am Soc Clin Oncol. 2009;27(19):3109–16.

https://doi.org/10.1200/JCO.2008.20.6771.

6. Gill S, Loprinzi CL, Sargent DJ, Thome SD, Alberts SR, Haller DG, etal. Pooled analysis of uorouracil-based adjuvant therapy for stage II and III colon cancer: who benets and by how much? J Clin Off J Am Soc Clin Oncol. 2004;22(10):1797–806. https://doi.org/10.1200/

JCO.2004.09.059.

7. Glimelius B, Dahl O, Cedermark B, Jakobsen A, Bentzen SM, Starkhammar H, etal. Adjuvant chemotherapy in colorectal cancer: a joint analysis of randomised trials by the Nordic gastrointestinal tumour adjuvant therapy group. Acta Oncol. 2005;44(8):904–12. https://doi.

org/10.1080/02841860500355900.

8. Moertel CG, Fleming TR, Macdonald JS, Haller DG, Laurie JA, Tangen CM, etal. Intergroup study of uorouracil plus levamisole as adjuvant therapy for stage II/dukes’ B2 colon cancer. J Clin Oncol Off J Am Soc Clin Oncol. 1995;13(12):2936–43.

9. Taal BG, Van Tinteren H, Zoetmulder FA.Group N.Adjuvant 5FU plus levamisole in colonic or rectal cancer: improved survival in stage II and III. Br J Cancer. 2001;85(10):1437–43.

https://doi.org/10.1054/bjoc.2001.2117.

10. Yothers G, O’Connell MJ, Allegra CJ, Kuebler JP, Colangelo LH, Petrelli NJ, etal. Oxaliplatin as adjuvant therapy for colon cancer: updated results of NSABP C-07 trial, including survival and subset analyses. J Clin. Oncol Off J Am Soc Clin Oncol. 2011;29(28):3768–74. https://doi.

org/10.1200/JCO.2011.36.4539.

11. André T, de Gramont A, Vernerey D, etal. Adjuvant uorouracil, Leucovorin, and Oxaliplatin in stage II to III colon cancer: updated 10-year survival and outcomes according to BRAF mutation and mismatch repair status of the MOSAIC study. J Clin Oncol. 2015;33(35):4176–87.

https://doi.org/10.1200/JCO.2015.63.4238.

12. Kumar A, Kennecke HF, Renouf DJ, Lim HJ, Gill S, Woods R, etal. Adjuvant chemotherapy use and outcomes of patients with high-risk versus low-risk stage II colon cancer. Cancer. 2015;121(4):527–34. https://doi.org/10.1002/cncr.29072.

13. O’Connor ES, Greenblatt DY, LoConte NK, Gangnon RE, Liou JI, Heise CP, etal. Adjuvant chemotherapy for stage II colon cancer with poor prognostic features. J Clin Oncol Off J Am Soc Clin Oncol. 2011;29(25):3381–8. https://doi.org/10.1200/JCO.2010.34.3426.

14. Casadaban L, Rauscher G, Aklilu M, Villenes D, Freels S, Maker AV. Adjuvant chemotherapy is associated with improved survival in patients with stage II colon cancer. Cancer. 2016;122(21):3277–87. https://doi.org/10.1002/cncr.30181.

15. NCCN Guidelines. Colon Cancer Version 3.2022. NCCN.org.

16. Babcock BD, Aljehani MA, Jabo B, etal. High-risk stage II colon cancer: not all risks are created equal. Ann Surg Oncol. 2018;25:1980–5. https://doi.org/10.1245/s10434- 018- 6484- 8.

17. Sinicrope FA.DNA mismatch repair and adjuvant chemotherapy in sporadic colon cancer. Nat Rev Clin Oncol. 2010;7(3):174–7. https://doi.org/10.1038/nrclinonc.2009.235.

18. Gavin PG, Colangelo LH, Fumagalli D, Tanaka N, Remillard MY, Yothers G, etal. Mutation proling and microsatellite instability in stage II and III colon cancer: an assessment of their prognostic and oxaliplatin predictive value. Clin Cancer Res Off J Am Assoc Cancer Res. 2012;18(23):6531–41. https://doi.org/10.1158/1078- 0432.CCR- 12- 0605.

19. Hutchins G, Southward K, Handley K, Magill L, Beaumont C, Stahlschmidt J, etal. Value of mismatch repair, KRAS, and BRAF mutations in predicting recurrence and benets from chemotherapy in colorectal cancer. J Clin. Oncol Off J Am Soc. 2011;29(10):1261–70. https://

doi.org/10.1200/JCO.2010.30.1366.

20. Klingbiel D, Saridaki Z, Roth AD, Bosman FT, Delorenzi M, Tejpar S.Prognosis of stage II and III colon cancer treated with adjuvant 5-uorouracil or FOLFIRI in relation to microsatellite status: results of the PETACC-3 trial. Ann Oncol Off J Eur Soc Med Oncol/ ESMO. 2015;26(1):126–32. https://doi.org/10.1093/annonc/mdu499.

21. Sargent DJ, Marsoni S, Monges G, Thibodeau SN, Labianca R, Hamilton SR, etal. Defective mismatch repair as a predictive marker for lack of efcacy of uorouracil-based adjuvant therapy in colon cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2010;28(20):3219–26. https://

doi.org/10.1200/JCO.2009.27.1825.

209

210

https://t.me/medicina_free

22. Gray RG, Quirke P, Handley K, Lopatin M, Magill L, Baehner FL, etal. Validation study of a quantitative multigene reverse transcriptase-polymerase chain reaction assay for assessment of recurrence risk in patients with stage II colon cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2011;29(35):4611–9. https://doi.org/10.1200/JCO.2010.32.8732.

23. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, etal. PD-1 blockade in tumors with mismatch-repair deciency. N Engl J Med. 2015;372(26):2509–20. https://doi.

org/10.1056/NEJMoa1500596.

24. Sinicrope FA, Foster NR, Thibodeau SN, Marsoni S, Monges G, Labianca R, etal. DNA mismatch repair status and colon cancer recurrence and survival in clinical trials of 5-uorouracilbased adjuvant therapy. J Natl Cancer Inst. 2011;103(11):863–75. https://doi.org/10.1093/

jnci/djr153.

25. Roth AD, Tejpar S, Delorenzi M, Yan P, Fiocca R, Klingbiel D, etal. Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial. J Clin Oncol Off J Am Soc Clin Oncol. 2010;28(3):466–74. https://doi.org/10.1200/JCO.2009.23.3452.

26. Watanabe T, Kobunai T, Yamamoto Y, Matsuda K, Ishihara S, Nozawa K, etal. Chromosomal instability (CIN) phenotype, CIN high or CIN low, predicts survival for colorectal cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2012;30(18):2256–64. https://doi.org/10.1200/

JCO.2011.38.6490.

27. Jover R, Zapater P, Castells A, Llor X, Andreu M, Cubiella J, etal. The efcacy of adjuvant chemotherapy with 5-uorouracil in colorectal cancer depends on the mismatch repair status. Eur J Cancer. 2009;45(3):365–73. https://doi.org/10.1016/j.ejca.2008.07.016.

28. Kim GP, Colangelo LH, Wieand HS, Paik S, Kirsch IR, Wolmark N, et al. Prognostic and predictive roles of high-degree microsatellite instability in colon cancer: a National Cancer Institute-National Surgical Adjuvant Breast and bowel project Collaborative study. J Clin Oncol Off J Am Soc Clin Oncol. 2007;25(7):767–72. https://doi.org/10.1200/JCO.2006.05.8172.

29. Sun X, Huang T, Cheng F, Huang K, Liu M, He W, Li M, Zhang X, Xu M, Chen S, Xia L.Monitoring colorectal cancer following surgery using plasma circulating tumor DNA.Oncol Lett. 2018;15(4):4365–75.

30. Tie J, Cohen JD, Lahouel K, etal. Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer. N Engl J Med. 2022;386(24):2261–72. https://doi.org/10.1056/

NEJMoa2200075.

31. Dasari A, Grothey A, Kopetz S.Circulating tumor DNA-dened minimal residual disease in solid tumors: opportunities to accelerate the development of adjuvant therapies [published online ahead of print, 2018 Oct 30]. J Clin Oncol. 2018;36(35):JCO2018789032. https://doi.

org/10.1200/JCO.2018.78.9032.

32. Iveson TJ, Sobrero AF, Yoshino T, etal. Duration of Adjuvant Doublet Chemotherapy (3 or 6 months) in Patients With High-Risk Stage II Colorectal Cancer [published correction appears in J Clin Oncol. 2021 May 20;39(15):1691]. J Clin Oncol 2021;39(6):631–641. doi:https://doi.

org/10.1200/JCO.20.01330.

G. Dosunmu and C.-Y. Liao

Is There aBenefit inCytoreduction

https://t.me/medicina_free

andHyperthermic Intraperitoneal

Chemotherapy inColorectal Cancer?

ArshaOstowari andOliverS.Eng

Introduction

Colorectal cancer (CRC) is the third most common type of cancer with 1.9 million new cases in 2020 and second in terms of cancer deaths with 935,000 deaths in 2020 [1]. The peritoneum is a common site of metastasis for CRC that is associated with poor prognosis. It is estimated that around 5% of patients with CRC are synchronously diagnosed with peritoneal carcinomatosis (PC) and a greater proportion ranging from 5–20% of CRC patients will develop metachronous PC later in their disease course [2–4]. Additionally, this is likely an under-estimation of PC incidence as tumor deposits are small (<1cm) and difcult to be captured on imaging alone, requiring more invasive procedures such as laparoscopy to better evaluate the abdomen [2–5]. Autopsy studies that have looked at patients who died from CRC found PC in up to 40% of patients [6]. This raises the importance of appropriately managing and treating patients with metastatic CRC, which has evolved over the past few decades with changes in the systemic and surgical treatment options available. Currently, cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) is a potential modality for treatment of patients with PC [7]. In the 2000s, as is summarized in Table18.1, studies showed that CRS/

A. Ostowari (*) Department of Surgery, University of California, Orange, CA, USA e-mail: ostowari@hs.uci.edu

O. S. Eng (*) Division of Surgical Oncology, Department of Surgery, University of California, Orange, CA, USA e-mail: oeng@uci.edu

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 K. Umanskiy, N. Hyman (eds.), Difcult Decisions in Colorectal Surgery, Difcult Decisions in Surgery: An Evidence-Based Approach,

https://doi.org/10.1007/978-3-031-42303-1_18

211

212

https://t.me/medicina_free

A. Ostowari and O. S. Eng

Table 18.1

Study Verwaal etal.

(2003)

Verwaal etal. (2008)

Glehen etal. (2004) 506 CRS/HIPEC 1y, 3y, 5y OS: 72%,

Franko etal. (2010) 67 vs. 38 CRS/HIPEC vs

Goéré etal. (2013) 107 CRS/IPC OS: 5year (35%),

Esquivel etal. ASPSM (PSDSS) (2014)

Prada-Villaverde etal. ASPSM (2014)

Summary of CRS/HIPEC studies

Participants (Treatment vs. Control) Study design Outcome

54 vs. 51 CRS/HIPEC vs

SCT

54 vs. 51 CRS/HIPEC vs

SCT

1013 CRS/HIPEC vs

SCT

539 CRS/HIPEC

(Oxaliplatin) vs CRS/HIPEC (Mitomycin)

Median OS: 22.3 vs

12.6m Median OS (complete reduction): 48m 45% alive at 5years

Median PFS: 12.6 vs

7.7m Median diseasespecic survival: 22.2 vs 12.6m

39%, 19% 1y, 3y, 5y DFS: 40%, 16%, 10% Median OS: 19.2m Median OS: CCR-0 (32.4m), CCR-1 (24m), CCR-2 (8.4m)

Median OS: 34.7 vs

16.8m

10year (15%) 16% cure rate PCI (cure vs noncured): 4 vs 12

Median OS: 41 vs 10m 3y OS: 66% vs 25% 5y OS: 58% vs 19% Median OS (PSDSS I/II/III/IV): 86 vs 49m, 43 vs 19m, 29 vs 8m, 28 vs 6m Median OS (CC-0/ CC≥1): 51 vs 28m

Median OS: 32.6m Median OS (PSDSS I/II): 28.2 vs 54.3m No OS difference between mitomycin and oxaliplatin

Quality of evidence

Moderate

(continued)

18 Is There a Benet in Cytoreduction and Hyperthermic Intraperitoneal…

https://t.me/medicina_free

Table 18.1 (continued)

Participants (Treatment

Study Cashin etal. (2016) 24 vs. 24 CRS/IPC vs SCT OS (2years): 54% vs

Klaver etal. COLOPEC (2019)

Goéré etal. PROPHYLOCHIP (2020)

Quénet etal. PRODIGE 7 (2021)

vs. Control) Study design Outcome

38% Median OS: 25 vs 18m Survival at 5years: 33% vs 4%

100 vs. 102 Adjuvant HIPEC

+ SCT vs SCT

75 vs. 71 2nd-look CRS/

HIPEC vs surveillance

133 vs 132 CRS/HIPEC vs

CRS

Peritoneal-free survival (18m):

80.9% vs 76.2% DFS (18m): 69% vs

69.3% OS (18m): 93% vs

94.1% Time to diagnosis of PM: 9 vs 14m

3y DFS: 44% vs 53% 3y peritoneal recurrence free survival: 59% vs 61% 3y OS: 79% vs 80% 5y OS: 68% vs 72% 41% in second-look group had grade 3–4 complications

No difference in OS or RFS At 30days, no difference in frequency of grade 3 or worse adverse events Between 30–60days, higher rate of grade 3 or worse adverse events in CRS/HIPEC group Subset with PCI 11–15, improved OS and RFS in CRS/ HIPEC

213

Quality of evidence

Low

High

HIPEC provide CRC patients with a signicant mortality benet when compared to standard chemotherapy (SCT) in the setting of PC [8]. Since then, CRS/HIPEC has been studied extensively in order to optimize the treatment modality and to determine if and who would benet most from CRS/HIPEC (Table18.1).

214

https://t.me/medicina_free

A. Ostowari and O. S. Eng

Search Strategy

A literature review was performed using the MEDLINE/PubMed database to identify relevant studies after the year 2000 using the following terms: “colorectal cancer”, “peritoneal carcinomatosis”, “cytoreductive surgery”, “Intraperitoneal chemotherapy”, “Adjuvant chemotherapy”, “HIPEC”, “Novel therapies”.

P (Patients) Patients with colorectal

cancer and peritoneal carcinomatosis

I (Intervention) C (Comparator) CRS/HIPEC Systemic

therapy, CRS alone

O (Outcomes) Overall Survival (OS),

Progression free survival (PFS), Disease free survival (DFS)

Results

In the 2000s, a sentinel study was carried out by Verwaal etal. that evaluated the efcacy of CRS/HIPEC versus SCT in patients with PC from CRC. 105 patients were enrolled in this study with 54 randomized to the CRS/HIPEC (Mitomycin C) arm and 51 to the control arm consisting of SCT (Fluorouracil, Leucovorin) with or without palliative surgery. At a median follow-up of 21.6months, the CRS/HIPEC arm exhibited a longer median survival of 22.3months compared to 12.6months (p=0.032) in the control arm [8]. Subgroup analyses of patients that underwent CRS/HIPEC showed that those with disease in 6–7 regions of the abdomen had poorer median survival compared to those patients with disease involvement of zero to ve regions (5.4months vs >29months, p<.0001) [8]. Additionally, only 1/18 patients who underwent a complete resection died versus 14/21 with limited residual disease and 7/10 with extensive residual disease (p<.0001) [8]. Overall, those whom underwent complete cytoreduction had a median OS of 48months with a 5-year survival of 45% [9]. The subgroup analyses within the experimental arm brought up two important concepts regarding CRS/HIPEC with improved survival in those with lower burden of disease, reported as the peritoneal carcinomatosis index (PCI), and the importance in achieving a complete cytoreduction. These results were additionally demonstrated in an 8-year follow up of the initial study by Verwaal et al. This study illustrated a durable survival benet when comparing CRS/HIPEC to SCT in the treatment of CRC patients with PC.This follow-up study showed an increased median progression-free survival in CRS/HIPEC of

12.6months vs 7.7 months and an improved median disease-specic survival of

22.2months vs 12.6 months [9]. Two limitations in this study were related to the

systemic chemotherapy and patient population, which can impact its generalizability to present day treatment of CRC patients. 5-FU/Leucovorin was used as the SCT, which is not the optimal rst-line therapy today and 17% of the patient cohort had a diagnosis of primary appendiceal malignancies [8]. Appendiceal cancer is a distinct malignancy from CRC with heterogeneous long-term oncologic outcomes that therefore may have affected the results of the study.

18 Is There a Benet in Cytoreduction and Hyperthermic Intraperitoneal…

https://t.me/medicina_free

215

In subsequent follow-up studies, Glehen etal. carried out a large retrospective multicenter study that further evaluated the efciency of CRS/HIPEC and additional prognostic indicators. This study included 506 patients from 28 institutions between May 1987 and December 2002 that underwent CRS and perioperative intraperitoneal chemotherapy. The overall morbidity and mortality rate in the patient cohort was 22.9% and 4% with a median OS of 19.2months [10]. When the patient cohort was sub-divided based on the completeness of cytoreduction, a signicantly improved survival benet was seen. Patients that underwent a complete cytoreduction (CCR-0) had a median OS of 32.4months versus 24months in CCR-1 patients and 8.4 months (p < 0.001) in those with an incomplete cytoreduction (CCR-2) [10]. Multivariate analysis showed that positive independent prognostic indicators included complete cytoreduction, treatment with a second procedure, limited PC, age<65 and use of adjuvant therapy, while negative prognostic indicators were the use of neoadjuvant chemotherapy, lymph node involvement, presence of liver metastasis and poor histologic differentiation. The completeness of cytoreduction was the principal independent prognostic indicator (p<0.0001) [10]. When subgroup analysis was performed based on the extent of PC, the OS of those with limited PC (PCI<13 and stage I and II from the Gilly’s classication) was higher than extended PC (PCI≥ 13 and stage III and IV from the Gilly’s classication) with 1-year, 3-year and 5-year OS of 92%, 50%, and 33% versus 62%, 22%, and 11%, respectively (p<0.0001) [10]. These ndings reafrmed some of the existing concepts introduced in the previous study regarding the prognostic benet of lower PC burden and improved survival with complete cytoreduction. In addition, this study addressed a limitation of the previous study by excluding all malignancies of appendiceal origin. However, in addition to the retrospective nature this study, authors acknowledged treatment variability, for example, in HIPEC technique regarding exposure, drugs, drug doses, duration, temperature, type of perfusate and ow rates [10]. Following this, a study carried out by Goéré etal. evaluated the long-term outcomes of CRS and intraperitoneal chemotherapy (IPC). This study looked at 107 patients from 1995 to 2006 who underwent complete CRS followed by IPC [11]. At a median follow up of 77months, the 5-year and 10-year OS was 35% and 15% and 16% of patients (n=17) were considered cured, dened as having a disease-free interval of at least 5years. Comparing patients that were considered cured to the rest of the cohort, a signicantly lower PCI was noted (4 vs 12, p=.0002). Additionally, after multivariate analysis, a PCI ≤ 10 was the only independent factor predictive of a cure in the patient population [11].

Franko etal. performed a single-institution retrospective case study that compared patients undergoing CRS/HIPEC versus modern SCT alone. 105 patients were included from 2001 to 2007 with 67 patients in the CRS/HIPEC (Mitomycin) arm and 38 patients in the SCT alone group. Median OS favored the CRS/HIPEC group at 34.7months compared to 16.8months in the SCT alone group (p<0.001) [12]. In addition, this study found that the presence of a liver metastasis was a signicant negative predictor of survival with a HR of 2.13 [12]. Following this, Cashin etal. designed a prospective, randomized control trial that compared patients undergoing CRS/IPC versus patients undergoing SCT alone. Unfortunately, this study

<<< < Предыдущая 11 12 13 14 15 16 17 18 19 20 21 2223 / 5023 24 25 26 27 28 29 30 31 32 33 34 35 > Следующая >>>

Соседние файлы в папке @xirurgi_2025

#
29.08.202622 Мб0@xirurgi_2025 - 587 - файл.pdf
#
29.08.202622 Мб0@xirurgi_2025 - 593 - файл.pdf
#
29.08.202622 Мб0@xirurgi_2025 - 594 - файл.pdf
#
29.08.202622 Мб0@xirurgi_2025 - 596 - файл.pdf
#
29.08.202622 Мб0@xirurgi_2025 - 597 - файл.pdf
#
29.08.202622 Мб0@xirurgi_2025 - 598 - файл.pdf
#
29.08.202622 Мб0@xirurgi_2025 - 599 - файл.pdf
#
29.08.202622 Мб0@xirurgi_2025 - 600 - файл.pdf
#
29.08.202622 Мб0@xirurgi_2025 - 602 - файл.pdf
#
29.08.202622 Мб0@xirurgi_2025 - 603 - файл.pdf
#
29.08.202621 Мб0@xirurgi_2025 - 606 - файл.djvu