Objective: To investigate an association between the gut microbiome and efficacy of poly(ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer. Methods: This study conducted fecal microbiome analysis (16S rRNA gene sequencing) and circulating tumor DNA (ctDNA) profiling for ovarian cancer patients who underwent PARPi maintenance therapy. Fecal and blood samples were collected at the baseline and the progressive disease (PD) or last follow-up. The relative abundance of gut microbes and progression-free survival (PFS) were analyzed using linear discriminant analysis of effect size and the Cox proportional hazard model according to BRCA1/2 mutation (BRCA1/2mut) status detected by ctDNA sequencing. Results: Baseline samples were available from 23 BRCA1/2mut-positive patients and 33 BRCA1/2mut-negative patients. The microbes enriched in the baseline samples with long PFS were Bifidobacterium, Roseburia, Dialister, Butyricicoccus, and Bilophila for BRCA1/2mut-positive patients and Phascolarctobacterium for BRCA1/2mut-negative patients. In multivariate analyses dividing patients by the median values of relative abundances, no bacteria were associated with PFS in BRCA1/2mut-positive patients, whereas high Phascolarctobacterium abundances (≥1.11%) was significantly associated with longer PFS in BRCA1/2mut-negative patients (median 14.0 vs. 5.9 months, hazard ratio=0.28; 95% confidence interval=0.11–0.69; p=0.014). In the last samples, the relative abundances of Phascolarctobacterium were significantly higher in patients without PD (n=5) than those with PD (n=15) (median 1.25% vs. 0.06%; p=0.016). Conclusion High fecal composition of Phascolarctobacterium was associated with prolonged PFS in patients with BRCA1/2mut-negative ovarian cancer receiving PARPi therapy. Our results would provide new insights for future research.

Purpose: Maintenance therapy after oxaliplatin withdrawal is useful in patients with metastatic colorectal cancer (mCRC). This study aimed to investigate the timing of discontinuation or reintroduction of oxaliplatin and the optimal maintenance therapy regimen for survival. Materials and Methods: PubMed and conference abstracts were searched to select phase II and III trials of first-line oxaliplatin-containing therapy with or without bevacizumab using maintenance therapy for mCRC. Correlations of median overall survival (OS) with induction therapy regimens, induction therapy duration, maintenance therapy regimens (fluoropyrimidine plus bevacizumab [FP+Bev], FP/Bev alone, and no treatment), and oxaliplatin reintroduction were investigated using correlation and weighted multivariate regression analyses. Results: Twenty-two treatment arms were analyzed, including 2,581 patients. The maintenance therapy regimen FP+Bev showed the strongest correlation with a prolonged OS (Spearman’s partial correlation coefficient=0.42), and the other three variables correlated weakly with the OS. The maintenance therapy regimen significantly interacted with the induction chemotherapy duration (p=0.019). The predicted OS for FP+Bev crossed the lines of FP/Bev alone at 18 weeks of induction therapy, and of no treatment at 23 weeks. The corresponding OS at 12 and 27 weeks of induction therapies were 28.6 and 24.2 months for FP+Bev, 25.9 and 28.8 months for FP/Bev alone, and 20.5 and 27.5 months for no treatment. Conclusion The optimal maintenance therapy regimen for the OS is a continuous induction therapy as long as possible followed by FP/Bev alone and switching to FP+Bev within approximately 4 months if induction therapy is discontinued.

Purpose: Maintenance therapy after oxaliplatin withdrawal is useful in patients with metastatic colorectal cancer (mCRC). This study aimed to investigate the timing of discontinuation or reintroduction of oxaliplatin and the optimal maintenance therapy regimen for survival. Materials and Methods: PubMed and conference abstracts were searched to select phase II and III trials of first-line oxaliplatin-containing therapy with or without bevacizumab using maintenance therapy for mCRC. Correlations of median overall survival (OS) with induction therapy regimens, induction therapy duration, maintenance therapy regimens (fluoropyrimidine plus bevacizumab [FP+Bev], FP/Bev alone, and no treatment), and oxaliplatin reintroduction were investigated using correlation and weighted multivariate regression analyses. Results: Twenty-two treatment arms were analyzed, including 2,581 patients. The maintenance therapy regimen FP+Bev showed the strongest correlation with a prolonged OS (Spearman’s partial correlation coefficient=0.42), and the other three variables correlated weakly with the OS. The maintenance therapy regimen significantly interacted with the induction chemotherapy duration (p=0.019). The predicted OS for FP+Bev crossed the lines of FP/Bev alone at 18 weeks of induction therapy, and of no treatment at 23 weeks. The corresponding OS at 12 and 27 weeks of induction therapies were 28.6 and 24.2 months for FP+Bev, 25.9 and 28.8 months for FP/Bev alone, and 20.5 and 27.5 months for no treatment. Conclusion The optimal maintenance therapy regimen for the OS is a continuous induction therapy as long as possible followed by FP/Bev alone and switching to FP+Bev within approximately 4 months if induction therapy is discontinued.

Background: Sulforaphane (SFN), a compound abundant in broccoli sprouts (BS), protects cells from oxidative injury by activating nrf2-mediated antioxidant enzymes. Sulforaphane also shows bactericidal activity against H. pylori in vitro. The aim of this study was to determine if daily intake of SFN-rich BS inhibits H. pylori colonization and mitigated gastritis in H. pylori-infected gastric mucosa in mice and humans.
Methods: Study 1: Nrf2+/+ and nrf2−/− C57BL/6 female mice were infected with H.pylori Sydney Strain; SS1. Mice were maintained for 2 mo. on a high salt diet (7.5% NaCl), supplemented with or without BS containing approximately 2.5 mM SFN. Degree of gastritis was evaluated by updated Sydney system. Study 2: Fifty subjects infected with H. pylori were randomly assigned to either the BS group (n=25) or the Alfalfa Sprouts (AS) group (n=25). All subjects were asked to eat BS 70 g/day (containing approximately 180 mg SFN) or AS 70 g/day (no SFN) for 2 months. H.pylori colonization was evaluated by measurement of HpSA. The degree of gastritis was evaluated by measuring serum levels of pepsinogen (PG) I and II.
Results: Study 1: BS treatment decreased Hp colonization and mitigated gastritis in nrf2+/+ but not in nrf2−/− mice. Study 2: Two months intervention with BS decreased HpSA values and serum levels of PG I and II, while AS showed on effect.
Conclusion: Daily intake of SFN-rich BS suppresses H.pylori colonization and improves gastritis in H. pylori-infected gastric mucosa via nrf2-dependent mechanisms.

Interest in complementary and alternative medicine (CAM) has grown rapidly, fueled by Internet marketing, dissatisfaction with mainstream medicine, and the desire of patients to be actively involved in their own health care. CAM products in cancer medicine (herbs and other natural products, such as shark cartilage, mushrooms, and so on) are widely available in Japan as well as in western countries. With little reliable information and few clinical trials to assess the efficacy of such products, there is a great need for public and professional education regarding this subject.