Need for adjuvant chemotherapy after colon cancer surgery – has it decreased?

Böckelman, Camilla; Glimelius, Bengt

doi:10.1080/0284186x.2017.1317924

Cited by 6 publications

(4 citation statements)

References 57 publications

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“…Colorectal cancer (CRC) is ranked as the third most common cancer in males and second in females, and the fourth leading cause of cancer-related deaths worldwide (1). For the patients with early CRC, surgery is the preferred treatment, and adjuvant chemotherapy is administered to most patients with CRC after surgery to decrease the risk of recurrence (2). However, the disease-free and overall survival of CRC patients warrants further improvement.…”

Section: Introductionmentioning

confidence: 99%

“…Accumulating evidence from basic studies suggests that the change of lipid levels is associated with human gene mutations that would influence the treatment and prognosis of cancer (9). It is well-known that a high-fat diet can easily cause CRC, and it has been reported that lipid metabolism is closely related to the initiation, development and metastasis of CRC (2). However, there have been few studies that address the difference in lipid metabolism between dMMR and pMMR CRC.…”

Section: Introductionmentioning

confidence: 99%

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LC‑MS/MS metabolome analysis detects the changes in the lipid metabolic profiles of dMMR and pMMR cells

Peng

Tan

et al. 2018

Oncol Rep

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The DNA mismatch repair (MMR) system plays an important role in the initiation, diagnosis and treatments of colorectal cancer (CRC). Compared to CRC patients deficient in DNA MMR (dMMR), CRC patients proficient in DNA MMR (pMMR) have higher metastasis, short survival and poor response to chemotherapy and immunotherapy. It is well‑known that a high‑fat diet can cause CRC, and lipid metabolism is closely related to the development and metastasis of CRC. However, there have been few studies that address the difference in lipid metabolism between dMMR and pMMR CRC. Liquid chromatography‑tandem mass spectrometry (LC/MS) is an advanced technique that can perform the analysis of lipid metabolites and the roles of lipids present in low abundance in cell signaling and membrane stability. In the present study, we used the LC/MS technique to analyze the difference in the lipid metabolic profiles between dMMR cell lines (HCT116, DLD1, LoVo and HCT15) and pMMR cell lines (SW480, SW620, HT29 and NCM460). The results revealed that, among the 19 classes and 157 intact lipid species identified by the LC/MS analysis, the levels of most phospholipids were lower in dMMR cells than pMMR cells. Higher levels of phosphatidylcholine (PC; 16:0/18:1) and phosphatidic acid (PA; 18:0/18:0) were observed in pMMR cells than in dMMR cells. Furthermore, our results revealed that SCD1 and PLD1, the key enzymes involved in lipid metabolism associated with metastasis, are higher in pMMR cells than dMMR cells. To the best of our knowledge, we are the first to reveal that the levels of metastasis‑associated lipids and key enzymes in lipid metabolism were higher in the CRC patients with pMMR compared with the CRC patients with dMMR. This study identified potential anti‑metastatic targets in the therapy of patients with pMMR, and also personalized therapy for the patients with pMMR.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

LC‑MS/MS metabolome analysis detects the changes in the lipid metabolic profiles of dMMR and pMMR cells

Peng

Tan

et al. 2018

Oncol Rep

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“…A few studies have recently substantiated that these risks are less than in the past [17][18][19]. Whether this knowledge will change routines is not known [20], but the Swedish guidelines valid from spring 2019 do not recommend adding oxaliplatin routinely to patients below 70 years of age as often as was the case in the guidelines from 2016 [21]. In patients over 70 years, oxaliplatin is not recommended in the adjuvant setting.…”

Section: How Much Less Is Seen If 3 Months Of Oxaliplatin Is Given?mentioning

confidence: 99%

Lessons learned from the maturation of a cancer drug: oxaliplatin in colorectal cancer

Glimelius

Nygren

2019

Acta Oncologica

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The addition of oxaliplatin to a fluoropyrimidine is reference treatment after colon cancer surgery in patients with stage III and in stage II if at least one high-risk criterium for recurrence is present [1-3]. Even if guidelines open for using a fluoropyrimidine alone, there is a tendency to add oxaliplatin whenever adjuvant chemotherapy is indicated, at least in stage III. Three randomized trials comparing adjuvant therapy for six months using a fluoropyrimidine with or without oxaliplatin showed that the combination improved disease-free survival (DFS) by approximately 20% (hazard ratios, HRs 0.80-0.82) [4-6]. Overall survival was also slightly improved (HRs 0.84-0.88). An average risk of recurrence of 30% after fluoropyrimidine treatment alone, typical for many stage III patients, means that six additional patients per 100 treated will not experience any recurrence if oxaliplatin was added. If the recurrence risk is higher, more treated patients are gained, but for many stage III patients, including most patients with stage II and high-risk criteria, the recurrence risk is less, and the gain from adding oxaliplatin is only a few percent. All treated patients are at risk of toxicity, including the oxaliplatin-induced chronic and often disabling neurotoxicity. The oxaliplatin-induced peripheral neuropathy (OIPN) was considered along with the gains in recurrence risk and survival when different scientific and clinical organizations such as ASCO and NCCN in the US and ESMO in Europe and national groups recommended an oxaliplatin combination for all stage III colon cancers and for stage II cancers with high-risk factors. The extent of the adverse effects, i.e. the downside of adding oxaliplatin was known from the clinical trials where the treating physicians graded the neurotoxicity according to one of a few recommended scales. Typically, acute peripheral neurotoxicity of grade 2 or higher was recorded in 30-50% of the patients and although chronic OIPN was seen, it was not considered extensive [4-6]. In the MOSAIC trial, grade 2 and 3 chronic neuropathy were seen in 4.8 and 1.3%, respectively, after 12 months and in 3.4 and 0.7%, respectively, after 4 years [4].

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“…During the years, I have also written editorials within my own field of interest, gastrointestinal oncology, most recently [29][30][31][32]. I hope it has not been easier for me to see strengths in manuscripts dealing with gastrointestinal oncology than in other areas of oncology; nor the opposite, i.e., seeing faults in such articles.…”

Section: Improvements For Acta Oncologica During the Past 25 Yearsmentioning

confidence: 99%

Forty-five years in oncology, 25 years with Acta Oncologica

Glimelius

2018

Acta Oncologica

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Need for adjuvant chemotherapy after colon cancer surgery – has it decreased?

Cited by 6 publications

References 57 publications

LC‑MS/MS metabolome analysis detects the changes in the lipid metabolic profiles of dMMR and pMMR cells

LC‑MS/MS metabolome analysis detects the changes in the lipid metabolic profiles of dMMR and pMMR cells

Lessons learned from the maturation of a cancer drug: oxaliplatin in colorectal cancer

Forty-five years in oncology, 25 years with Acta Oncologica

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