Cyclophosphamide-dacarbazine-vincristine regimen is recommended for the treatment of malignant pheochromocytoma and paraganglioma (MPP); however, dacarbazine is the only recognized active drug in neuroendocrine tumours. We investigated the therapeutic benefit of temozolomide (TMZ), an oral alternative to dacarbazine, in patients with MPP. This is a retrospective study of consecutive patients with documented progressive MPP. We examined the correlation between Succinate dehydrogenase B (SDHB) mutation and O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation and MGMT expression in the French nation-wide independent cohort of 190 pheochromocytomas or paragangliomas (PP). Progression-free survival (PFS) according to RECIST 1.1 and PERCIST 1.0 criteria was the primary end point. Fifteen consecutive patients with MPP were enrolled; ten (67%) carried a mutation in SDHB. The mean dose intensity of TMZ was 172 mg/m 2 /d for 5 days every 28 days. Median PFS was 13.3 months after a median follow-up of 35 months. There were five partial responses (33%), seven stable (47%) and three progressive diseases (20%). Grade 3 toxicities were lymphopenia in two patients and hypertension in one. Partial responses were observed only in patients with mutation in SDHB. MGMT immunohistochemistry was negative in tumour samples from four patients who responded to treatment. SDHB germline mutation was associated with hypermethylation of the MGMT promoter and low expression of MGMT in 190 samples of the French nation-wide independent cohort. This study demonstrates that TMZ is an effective antitumour agent in patients with SDHB-related MPP. The silencing of MGMT expression as a consequence of MGMT promoter hypermethylation in SDHB-mutated tumours may explain this finding.Key words: malignant pheochromocytoma, paraganglioma, O(6)-methylguanine-DNA methyltransferase (MGMT), succinate dehydrogenase B (SDHB), temozolomide Additional Supporting Information may be found in the online version of this article. Malignant pheochromocytoma and paraganglioma (PP) are frequently associated with mutations in succinate dehydrogenase B (SDHB). We found a correlation between mutations in SDHB and hypermethylation of the promoter of O6-methylguanine-DNA methyltransferase (MGMT) in tumour samples from a French cohort of 190 patients with PP. Temozolomide yielded a clinical benefit in 67% of 15 patients treated for progressive malignant PP. The expression of MGMT was deficient in tumour samples from four of the five patients who responded to treatment. These results suggest that a personalized therapeutic approach may be applicable to this rare cancer.

Selection criteria for high-risk patients appear to be accurate. In these patients, the second-look strategy treated peritoneal carcinomatosis preventively or at an early stage, yielding promising results. This study has allowed us to design a multicentric randomized trial (comparing the second-look + HIPEC approach versus standard follow-up alone), which is beginning.

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Rectal resection via the transanal approach combined with single-port laparoscopic assistance may be easier and safer than the traditional approach, especially in male patients who have a narrow pelvis. More data are needed in order to draw conclusions concerning oncologic results and before selecting the most appropriate indications for this technique.

Evidence regarding the incidence of recurrent PC after curative surgery for colorectal cancer is poor. Emerging data indicate three situations that could result in a real higher risk of recurrent PC: synchronous PC, synchronous isolated ovarian metastases, and a perforated primary tumor.