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Articles on Gastrointestinal Cancer

A selection of peer-reviewed articles on Gastrointestinal Cancer. All content available on the Advances in Gastrointestinal Cancer Resource Center, including original and review articles, interviews, guidelines and congress highlights, is independently selected by the members of the Editorial Board.


  • Clinical T2N0 Esophageal Cancer: Identifying Pretreatment Characteristics Associated With Pathologic Upstaging and the Potential Role for Induction Therapy

    Samson P, Puri V, Robinson C, Lockhart C, Carpenter D, Broderick S, Kreisel D, Krupnick AS, Patterson GA, Meyers B, Crabtree T

    Ann Thorac Surg. 2016 Apr 12. [Epub ahead of print]
    Editorial comment from Professor David Cunningham:
    The implications of understaging are also highlighted in a manuscript by Samson et al. in Annals of Thoracic Surgery. The authors reviewed the cases of 932 clinically stage T2N0 patients who received upfront surgery, and 853 clinical T2N0 patients who received induction therapy prior to surgery. Almost half (45.7%) of patients who underwent upfront surgery were upstaged at surgery, of these 44.2% received adjuvant chemotherapy. For patients upstaged at upfront resection median overall survival was worse than for patients who received neoadjuvant chemotherapy (43.9 months versus 27.5 months, p < 0.001), however this difference was mitigated in patients who received adjuvant chemotherapy following upfront surgery (43.8 months versus 34.6 months, p = 0.14). However, as approximately half of patients do not have a performance status sufficient to allow safe delivery of adjuvant therapy following oesophagogastrectomy, neoadjuvant treatment is likely to be helpful for a greater number of patients.
  • Multicentre study of neoadjuvant chemotherapy for stage I and II oesophageal cancer

    Bekkar S, Gronnier C, Renaud F, Duhamel A, Pasquer A, Théreaux J, Gagnière J, Meunier B, Collet D, Mariette C; French Eso-Gastric Tumors (FREGAT) working group, Fédération de Recherche EN CHirurgie (FRENCH) and Association Française de Chirurgie (AFC)

    Br J Surg. 2016 Apr 4. [Epub ahead of print]
    Editorial comment from Professor David Cunningham:
    This month, there are a number of interesting studies published relating to the neoadjuvant treatment of oesophageal cancer. In the British Journal of Surgery, Bekkar et al. present the results of a large retrospective European study on the effects of neoadjuvant chemoradiotherapy on Stage I and II oesophageal cancer, a group of patients which are less well represented in clinical trials. Using propensity matched scoring to adjust for differences in baseline characteristics, they demonstrate that patients treated with neoadjuvant chemotherapy (typically cisplatin and fluoropyrimidine based) had better disease free and overall survival compared to those who did not receive pre-operative chemotherapy. The improvement in overall survival appeared to be driven by a reduction in distant metastases (21.9% vs. 27.1%; p = 0·035) as loco-regional recurrences and mixed recurrences occurred at similar rates in both groups. The study emphasised that understaging is common in patients with clinical Stage I and II disease, almost one third of patients had pathological stage III disease at surgery. This further supports a neo-adjuvant chemotherapy approach as micrometastases which lead to recurrence are more common in Stage III cancers and these may be eliminated by chemotherapy.
  • An accidental finding of gastric adenocarcinoma in a 51-year-old man

    Patient case presented by Dr. Peter Grell (Czech Republic)

    Introduction Here we describe a case of adenocarcinoma of the gastric fundus in a relatively young man who had no...
  • Quality-of-life and performance status results from the phase III RAINBOW study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated gastric or gastroesophageal junction adenocarcinoma

    Al-Batran SE, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S

    Ann Oncol 2016 Jan 7. pii: mdv625. [Epub ahead of print]
    Editorial comment from Professor Florian Lordick:
    The phase III RAINBOW trial demonstrated that the addition of ramucirumab to paclitaxel improved overall survival, progression-free survival, and tumor response rate in fluoropyrimidine–platinum previously treated patients with advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma. In this secondary publication, patient-reported outcomes were assessed with the QoL/health status questionnaires EORTC QLQ-C30 and EQ-5D at baseline and 6-week intervals. Performace status was assessed at baseline and day 1 of every cycle. Time to deterioration (TtD) in each QLQ-C30 scale was defined as randomization to first worsening of ≥10 points (on 100-point scale) and TtD in PS was defined as first worsening to ≥2. This associated study shows that in patients with previously treated advanced gastric/GEJ adenocarcinoma, addition of ramucirumab to maintained patient QoL and delayed symptom worsening and functional status deterioration.
    In conclusion, the QoL assessment of RAINBOW confirms the therapeutic value of second-line addition of ramucirumab to paclitaxel.
  • Chemotherapy vs supportive care alone for relapsed gastric, gastroesophageal junction, and oesophageal adenocarcinoma: a meta-analysis of patient-level data

    Janowitz T, Thuss-Patience P, Marshall A, Kang JH, Connell C, Cook N, et al.

    Br J Cancer 2016 Feb 16;114(4):381-7
    Editorial comment from Professor Florian Lordick:
    Until 2011, the value of second-line chemotherapy for advanced gastric cancer was not yet confirmed in prospective randomized studies. Meanwhile, several studies could confirm that either irinotecan or taxanes (docetaxel or paclitaxel) are effective in this setting. The latest studies (REGARD and RAINBOW) could demonstrate that ramucirumab given as a monotherapy in platinum-fluoropyrimidine pretreated patients with advanced gastric cancer prolongs survival in comparison to best supportive care alone. If added to paclitaxel monotherapy, ramucirumab also prolongs survival, progression-free survival and increases the overall response rate.
    The newly published meta-analysis of patient-level data confirms that second-line chemotherapy treatment results in significantly better OS compared with SC alone in patients with platinum and fluoropyrimidine refractory gastric and oesophageal adenocarcinoma. Health-related quality of life outcomes should be included in future trials in this setting, as the authors state.
  • Prognostic value of tumor-infiltrating lymphocytes in Epstein-Barr virus-associated gastric cancer

    Kang BW, Seo AN, Yoon S, Bae HI, Jeon SW, Kwon OK, etal.

    Ann Oncol. 2016 Mar;27(3):494-501
    Editorial comment from Professor Florian Lordick:
    The Cancer Genome Atlas (TCGA) network has divided gastric cancer into four distinct molecular subtypes, one of which being associated with the presence of Epstein-Barr-Virus (EBV) in gastric carcinoma cells. This subtype constitutes 5-10% of gastric cancers according to the current literature and seems to be associated with a somewhat better prognosis. EBV-associated gastric cancer often displays heavily infiltrating lymphoid elements and is also associated with inflammatory stroma and a rich cytokine milieu. This study explored the prognostic impact of tumor-infiltrating lymphocytes (TILs) and investigated whether three histologic subtypes (lymphoepithelioma-like carcinoma, carcinoma with Crohn’s disease-like lymphoid reaction, and conventional-type adenocarcinoma) could stratify a prognostic subset for patients with Epstein–Barr virus -associated gastric cancer. In an analysis of 120 patients with EBV-associated gastric cancer, stroma-TIL-positivity was significantly associated with longer recurrence-free survival (P = 0.002) and disease-free survival (P = 0.008), yet not overall survival. This is the first study that assessed the prognostic value of TILs in EBV-associated gastric cancer. The current findings support the concept that TILs can exert an antitumor effect through the host cellular immune response. Thus, the TILs in EBV-associated gastric cancer could be a stratification parameter and prognostic factor for predicting patient outcome. Further investigation is needed to determine the precise biologic significance of the inflammatory response in EBV-associated gastric cancer, as the authors conclude.
  • Influence of Surgical Resection of Hepatic Metastases From Gastric Adenocarcinoma on Long-term Survival: Systematic Review and Pooled Analysis

    Markar SR, Mikhail S, Malietzis G, Athanasiou T, Mariette C, Sasako M, Hanna GB

    Ann Surg. 2016 Jan 16. [Epub ahead of print]
    Editorial comment from Professor Florian Lordick:
    The pooled analysis of 39 studies, published by Markar and co-authors shows that long-term survival in stage IV M1 (hep) gastric cancer patients is achievable with hepatic resections. Morbidity associated with hepatectomy was 24% and postoperative mortality was 0%. Compared with chemotherapy alone, resection of hepatic metastases was associated with improved survival. Patients with solitary metastases had a better survival compared with multiple metastases. In contrast, metachronous versus synchronous metastases was not a significant prognostic factor. It is important to note that this study did not include patients with peritoneal metastases or other nonliver metastatic sites.
    The limitation of this study is that it is a pooled analysis of mostly small case-control studies, most of them coming from East Asia. Therefore, conclusions should be drawn with caution. To validate these findings and to learn more about the value and limitations of hepatic resections in stage IV gastric cancer, JCOG in cooperation with the EORTC is now planning a prospective registration study on hepatic resections in stage IV M1 (hep) gastric cancer.
  • Gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor (REGATTA): a phase 3, randomised controlled trial

    Fujitani K, Yang HK, Mizusawa J, Kim YW, Terashima M, Han SU, et al.

    Lancet Oncol. 2016 Mar;17(3):309-18
    Editorial comment from Professor Florian Lordick:
    The value of palliative gastrectomy in patients with metastatic gastric cancer has been debated since long time. As data from prospective randomized trials were lacking, clear recommendations could not be given. The East Asian “Gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor (REGATTA)” study is now filling this gap. The authors aimed to investigate the superiority of gastrectomy followed by chemotherapy versus chemotherapy alone in patients with advanced gastric cancer with a single non-curable factor. An open-label, randomised, phase 3 trial was conducted at 44 centres in Japan, South Korea, and Singapore. Patients aged 20–75 years with advanced gastric cancer with a single non-curable factor confined to either the liver, peritoneum, or para-aortic lymph nodes were randomly assigned (1:1) to chemotherapy alone (cisplatin and S-1) or gastrectomy followed by chemotherapy. Gastrectomy was restricted to D1 lymphadenectomy without any resection of metastatic lesions. 175 patients were randomly assigned to chemotherapy alone (86 patients) or gastrectomy followed by chemotherapy (89 patients). Gastrectomy followed by chemotherapy did not show any survival benefit compared with chemotherapy alone. Overall survival at 2 years for all randomly assigned patients was 31·7% for patients assigned to chemotherapy alone compared with 25·1% for those assigned to gastrectomy plus chemotherapy. Median overall survival was 16·6 months for patients assigned to chemotherapy alone and 14·3 months for those assigned to gastrectomy plus chemotherapy. The incidence of grade 3 or 4 chemotherapy-associated leucopenia, anorexia, nausea, and hyponatraemia was higher in patients assigned to gastrectomy plus chemotherapy than in those assigned to chemotherapy alone. The authors conclude: Since gastrectomy followed by chemotherapy did not show any survival benefit compared with chemotherapy alone in advanced gastric cancer with a single non-curable factor, gastrectomy cannot be justified for treatment of patients with these tumours.
    The REGATTA study results argue against palliative gastrectomy in patients who cannot be cured from metastatic gastric cancer. However, the current debate expands to the question, if a more radical surgical approach that includes metastatic sites (if these are technically resectable) may not confer a survival benefit in stage IV gastric cancer. A prospective randomized study investigating this question (Renaissance/FLOT-5 study) has started accrual in 2016; in addition, JCOG in cooperation with the EORTC is planning a prospective registration study on hepatic resections in stage IV M1 (hep) gastric cancer.

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