Prognostic value of specific KRAS mutations in patients with colorectal peritoneal metastases.

BACKGROUND: There is little evidence on KRAS mutational profiles in colorectal cancer (CRC) peritoneal metastases (PM). This study aims to determine the prevalence of specific KRAS mutations and their prognostic value in a homogeneous cohort of patients with isolated CRC PM treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. MATERIALS AND METHODS: Data were collected from 13 Italian centers, gathered in a collaborative group of the Italian Society of Surgical Oncology. KRAS mutation subtypes have been correlated with clinical and pathological characteristics and survival [overall survival (OS), local (peritoneal) disease-free survival (LDFS) and disease-free survival (DFS)]. RESULTS: KRAS mutations occurred in 172 patients (47.5%) out of the 362 analyzed. Two different prognostic groups of KRAS mutation subtypes were identified: KRASMUT1 (G12R, G13A, G13C, G13V, Q61H, K117N, A146V), median OS > 120 months and KRASMUT2 (G12A, G12C, G12D, G12S, G12V, G13D, A59E, A59V, A146T), OS: 31.2 months. KRASMUT2 mutations mainly occurred in the P-loop region (P < 0.001) with decreased guanosine triphosphate (GTP) hydrolysis activity (P < 0.001) and were more frequently related to size (P < 0.001) and polarity change (P < 0.001) of the substituted amino acid (AA). When KRASMUT1 and KRASMUT2 were combined with other known prognostic factors (peritoneal cancer index, completeness of cytoreduction score, grading, signet ring cell, N status) in multivariate analysis, KRASMUT1 showed a similar survival rate to KRASWT patients, whereas KRASMUT2 was independently associated with poorer prognosis (hazard ratios: OS 2.1, P < 0.001; DFS 1.9, P < 0.001; LDFS 2.5, P < 0.0001). CONCLUSIONS: In patients with CRC PM, different KRAS mutation subgroups can be determined according to specific codon substitution, with some mutations (KRASMUT1) that could have a similar prognosis to wild-type patients. These findings should be further investigated in larger series.

Treatment efficacy with electrochemotherapy: A multi-institutional prospective observational study on 376 patients with superficial tumors.

BACKGROUND: Cutaneous metastases represent a therapeutic challenge. An increasing body of experience suggests that electrochemotherapy (ECT) provides effective tumor control, although its evidence basis should be strengthened. METHODS: This prospective, multicenter, observational study enrolled patients with superficial metastases, who underwent ECT at 10 centers between 2008 and 2013. Outcomes included adherence to European Standard Operating Procedures of ECT (ESOPE), tumor response, local progression-free survival (LPFS), toxicity and patient-reported outcomes (PROs, EORTC QLQ-C30 plus an 8-item questionnaire). RESULTS: We enrolled 376 eligible patients. Tumor histotype distribution was as follows: melanoma, 56%; squamous cell carcinoma, 11%; Kaposi sarcoma, 11%; breast carcinoma, 8%; basal cell carcinoma, 6%; soft tissue sarcomas, 3%; others, 5%. We registered 1304 target tumors (median size 1 cm). Treatment adhered to ESOPE in 88% of patients as to the route of drug administration, and in 70% as to electrode application. The procedure was mainly performed under sedation (64.6%) and by using intravenous chemotherapy (93.4%). Tumor response rate at 60 days was 88% (complete, 50%). Small tumor size predicted complete response achievement (OR 2.24, p = 0.003), higher LPFS (HR 0.68, p = 0.004) and improved PROs (Global Health Status, p < 0.001; wound bleeding, p < 0.001; healing, p = 0.002; and aesthetics, p < 0.001). Skin toxicity (grade ≥3, 7.8%) was lower in patients with tumors <2 cm (p≤0.001). One-year LPFS was 73.7% (95%CI 68.4-78.3). CONCLUSIONS: ECT represents a valuable skin-directed therapy across a range of malignancies. The most frequently applied treatment modality is intravenous chemotherapy under sedation. Small tumor size predicts durable tumor control, fewer side-effects and better PROs.

[Neoadjuvant radiochemotherapy of rectal carcinoma: retrospective analysis of a personal experience]. / Radiochemioterapia neoadiuvante nel carcinoma del retto analisi retrospettiva di un'esperienza personale.

Even if surgical resection continues to be the mainstay of treatment in rectal cancer, preoperative chemoradiation may downstage locally advanced rectal cancer, in some cases with no residual tumors. Compared with surgery alone, preoperative radiotherapy and chemotherapy improves outcomes in patients with locally advanced rectal cancer. In the present review we summarize the results of preoperative chemoradiation therapy in a group of 15 patients who underwent surgical resection with total mesorectal excision (TME) for advanced mid and low rectal cancer from February 2002 to February 2004.

[Multimodal treatment of gastric MALT lymphoma: our experience]. / Trattamento multimodale del linfoma malt gastrico nostra esperienza.

Primary gastric lymphoma (PGL) is rare, but its incidence is increasing. It represents 52% of all extranodal GI tract lymphomas. The majority of PGLs are B cell non-Hodgkin's lymphomas or a high grade, diffuse, large cell lymphoma. The development of gastric mucosa associated lymphoid tissue is dependent on Helicobacter pylori infection. From January 2000 to February 2004, 10 patients were observed in the Unit of Surgical Oncology at Morgagni-Pierantoni Hospital in Forlì (6 F, 4 M), mean age was 68.3 (range, 45-86). Diagnosis was made in all patients by endoscopy and biopsies of gastric mucosa, US endoscopy and TC-PET. According to the Ann-Arbor classification modified by Musshoff, 6 patients were stage IE(1), 1 IE(2), 1 IIIE. 2 IV. Four and two patients underwent distal or total gastrectomy. respectively. Chemotherapy was performed in three patients, RT in one patient. Complete remission was observed in patients submitted to surgery and chemotherapy alone. No mortality and morbidity were observed. The treatment of LGP is not standardized yet. The role of surgery in the treatment of primary gastric lymphoma has been recently re-evaluated. Traditionally surgical treatment was aggressive, more recently radical gastrectomy is disputed and considered unnecessary. Conservative surgery and combined treatment is considered more appropriate for localized gastric lymphoma.

[Intraperitoneal chemotherapy with oxaliplatin after complete cytoreduction for peritoneal carcinomatosis from colorectal carcinoma: preliminary experience]. / Chemioipertermia intraperitoneale con oxaliplatino dopo citoriduzione completa per carcinosi peritoneale da carcinoma colorettale: esperienza preliminare.

Colorectal cancer with peritoneal carcinomatosis is usually considered incurable. Intraperitoneal carcinomatosis accounts for 25-35% of recurrences of colorectal cancer. Studies demonstrate that peritoneal carcinomatosis is not necessarily a terminal condition with no options for treatment or cure. Encouraging results were obtained in many studies by cytoreductive surgery followed by hyperthermic intraoperative intraperitoneal chemotherapy (HIIC). Oxaliplatin is a new agent whose clinical use with intraperitoneal administration has been pioneered by Elias et al. Eight patients with peritoneal carcinomatosis (PC) of colo-rectal origin underwent complete cytoreductive surgery from March 2004 to January 2005. Six of them were submitted to HIIC with semi-closed technique; in one patient mitomycin C (2 mg/m2/l) was used for intraperitoneal perfusion at 41.5-42 degrees for 60 minutes; in five patients IPCH was carried out for 30 minutes at 41.5-42 degrees with intraperitoneal oxaliplatin (460 mg/m2). Patients received intravenous leucovorin (10 mg/m2) and 5-fluorouracil (400 mg/m2) just before HIIC to maximize the effect of oxaliplatin. Preliminary results are reported.