РЕЗУЛЬТАТЫ ДОБАВЛЕНИЯ ПАНИТУМУМАБА К КОНВЕРСИОННОЙ ТЕРАПИИ КОЛОРЕКТАЛЬНОГО РАКА С МЕТАСТАЗАМИ В ПЕЧЕНЬ

Panitumumab has been shown to increase progression free and overall survival in patients with metastatic colorectal cancer.Our purpose was to evaluate whether panitumumab is effective and safe in patients with potentially resectable colorectal liver metastases (CRLM).Methods. Consecutive analysis of data from 11 patients (KRAS wild) receiving oxaliplatin-based chemotherapy and panitumumab as converse preoperative treatment for potentially resectable CRLM. At the moment of presentation R0-liver resection was not possible due to technical reasons (small remnant volume, large liver vessels involvement etc.). We studied objective response rate, surgical characteristics, skin toxicity profile, and perioperative course. Also expression of EGFR-ligands (transforming growth factor-α and amphiregulin) and   expression of E-cadherin were studied.Results. After median 6 courses of treatment, metastatic liver tumors were reduced considerably (PR) in 8 pts (73 %). Radical liver resection (R0) with 3 median number of removed segments was done in 6 (55 %) patients. Two pts underwent successfully the two-stage surgery (1 – portal vein embolization and 1 – portal vein ligation with partial left resection). Two patients progressed on chemotherapy (18 %). There was no correlation between skin toxicity and response. Mean blood loss was 250 ml. Preoperative administration of panitumumab was associated with higher risk of postoperative infection complication (57.1 %).Conclusions. To the best of our knowledge this is the first report about using panitumumab as conversion therapy before liver resection. The panitumumab and oxaliplatine-based regimen may increase the resection rate of liver metastases and influence on adhesive and proliferative activity of cancer cells. It is necessary to focus on postoperative infection complications.Доказано, что панитумумаб увеличивает выживаемость без прогрессирования и общую выживаемость у пациентов с метастазами колоректального рака (КРР) в печень.Целью нашего исследования стала оценка безопасности и эффективности добавления панитумумаба к лечению пациентов с потенциально резектабельными метастазами.Методы. В когортное проспективное исследование были включены 11 пациентов (дикий тип KRAS) с метастазами КРР в печень, расцененные исходно как «потенциально резектабельные» и получившие в качестве конверсионной предоперационной терапии панитумумаб в сочетании с химиотерапией на основе оксалиплатина в отделении хирургии печени, поджелудочной железы и желчных путей ФГБУ «РНЦХ им. акад. Б.В. Петровского» РАМН. К исследуемым параметрам относились частота и процент объективного ответа по критериям RECIST 1.1, оценка частоты выполнения резекции в объеме R0, интраоперационные и послеоперационные показатели, такие как кровопотеря во время операции, продолжительность операции, длительность пребывания в стационаре, осложнения, 30-дневная и 90-дневная летальность. Также изучалась экспрессия лигандов рецептора эпидермального фактора роста (EGFR) – трансформирующего фактора роста и амфирегулина, а также E-кадгерина.Результаты. После в среднем 6 курсов лечения частичный объективный ответ был зарегистрирован в 73 % случаев. Радикальную резекцию печени с удалением в среднем 3 сегментов удалось выполнить в один этап у 6 (55 %) пациентов. Два пациента успешно завершили двухэтапное лечение (1 – эмболизация воротной вены и 1 – перевязка правой воротной вены с сегментарной левосторонней резекцией). У 2 пациентов была зафиксирована прогрессия на фоне лечения. Корреляция между степенью выраженности кожной токсичности и объективным ответом отсутствовала. Медиана кровопотери составила 250 мл. Предоперационная терапия панитумумабом сопровождалась повышенным риском послеоперационных инфекционных осложнений (57,1 %).Выводы. По нашим данным, это первое исследование, в котором изучалось добавление панитумумаба к конверсионной терапии метастатического КРР до резекции печени. Режим лечения с использованием панитумумаба и оксалиплатина может увеличить частоту успешных резекций печени и влиять на адгезивные и пролиферативные свойства опухолевых клеток. Необходимо уделять внимание возможности развития послеоперационных инфекционных осложнений.

Impact of Preoperative Chemotherapy Features on Patient Outcomes after Hepatectomy for Initially Unresectable Colorectal Cancer Liver Metastases: A LiverMetSurvey Analysis

Background: Prognostic factors have been extensively reported after resection of colorectal liver metastases (CLM); however, specific analyses of the impact of preoperative systemic anticancer therapy (PO-SACT) features on outcomes is lacking. Methods: For this real-world evidence study, we used prospectively collected data within the international surgical LiverMetSurvey database from all patients with initially-irresectable CLM. The main outcome was Overall Survival (OS) after surgery. Disease-free (DFS) and hepatic-specific relapse-free survival (HS-RFS) were secondary outcomes. PO-SACT features included duration (cumulative number of cycles), choice of the cytotoxic backbone (oxaliplatin- or irinotecan-based), fluoropyrimidine (infusional or oral) and addition or not of targeted monoclonal antibodies (anti-EGFR or anti-VEGF). Results: A total of 2793 patients in the database had received PO-SACT for initially irresectable diseases. Short (<7 or <13 cycles in 1st or 2nd line) PO-SACT duration was independently associated with longer OS (HR: 0.85 p = 0.046), DFS (HR: 0.81; p = 0.016) and HS-RFS (HR: 0.80; p = 0.05). All other PO-SACT features yielded basically comparable results. Conclusions: In this international cohort, provided that PO-SACT allowed conversion to resectability in initially irresectable CLM, surgery performed as soon as technically feasible resulted in the best outcomes. When resection was achieved, our findings indicate that the choice of PO-SACT regimen had a marginal if any, impact on outcomes.info:eu-repo/semantics/publishedVersio

RESULTS OF PANITUMUMAB ADDITION TO CONVERSION THERAPY FOR COLORECTAL CANCER LIVER METASTASES

Panitumumab has been shown to increase progression free and overall survival in patients with metastatic colorectal cancer.Our purpose was to evaluate whether panitumumab is effective and safe in patients with potentially resectable colorectal liver metastases (CRLM).Methods. Consecutive analysis of data from 11 patients (KRAS wild) receiving oxaliplatin-based chemotherapy and panitumumab as converse preoperative treatment for potentially resectable CRLM. At the moment of presentation R0-liver resection was not possible due to technical reasons (small remnant volume, large liver vessels involvement etc.). We studied objective response rate, surgical characteristics, skin toxicity profile, and perioperative course. Also expression of EGFR-ligands (transforming growth factor-α and amphiregulin) and   expression of E-cadherin were studied.Results. After median 6 courses of treatment, metastatic liver tumors were reduced considerably (PR) in 8 pts (73 %). Radical liver resection (R0) with 3 median number of removed segments was done in 6 (55 %) patients. Two pts underwent successfully the two-stage surgery (1 – portal vein embolization and 1 – portal vein ligation with partial left resection). Two patients progressed on chemotherapy (18 %). There was no correlation between skin toxicity and response. Mean blood loss was 250 ml. Preoperative administration of panitumumab was associated with higher risk of postoperative infection complication (57.1 %).Conclusions. To the best of our knowledge this is the first report about using panitumumab as conversion therapy before liver resection. The panitumumab and oxaliplatine-based regimen may increase the resection rate of liver metastases and influence on adhesive and proliferative activity of cancer cells. It is necessary to focus on postoperative infection complications

Surgical management of patients with colorectal cancer and simultaneous liver and lung metastases

The management of patients with colorectal cancer and simultaneously diagnosed liver and lung metastases (SLLM) remains controversial

Liver-First Approach for Synchronous Colorectal Metastases: Analysis of 7360 Patients from the LiverMetSurvey Registry

Background: The liver-first approach in patients with synchronous colorectal liver metastases (CRLM) has gained wide consensus but its role is still to be clarified. We aimed to elucidate the outcome of the liver-first approach and to identify patients who benefit at most from this approach. Methods: Patients with synchronous CRLM included in the LiverMetSurvey registry between 2000 and 2017 were considered. Three strategies were analyzed, i.e. liver-first approach, colorectal resection followed by liver resection (primary-first), and simultaneous resection, and three groups of patients were analyzed, i.e. solitary metastasis, multiple unilobar CRLM, and multiple bilobar CRLM. In each group, patients from the three strategy groups were matched by propensity score analysis. Results: Overall, 7360 patients were analyzed: 4415 primary-first, 552 liver-first, and 2393 simultaneous resections. Compared with the other groups, the liver-first group had more rectal tumors (58.0% vs. 31.2%) and higher hepatic tumor burden (more than three CRLMs: 34.8% vs. 24.0%; size &gt; 50&nbsp;mm: 35.6% vs. 22.8%; p&nbsp;&lt;&nbsp;0.001). In patients with solitary and multiple unilobar CRLM, survival was similar regardless of treatment strategy, whereas in patients with multiple bilobar metastases, the liver-first approach was an independent positive prognostic factor, both in unmatched patients (3-year survival 65.9% vs. primary-first 60.4%: hazard ratio [HR] 1.321, p&nbsp;=&nbsp;0.031; vs. simultaneous resections 54.4%: HR 1.624, p&nbsp;&lt;&nbsp;0.001) and after propensity score matching (vs. primary-first: HR 1.667, p&nbsp;=&nbsp;0.017; vs. simultaneous resections: HR 2.278, p&nbsp;=&nbsp;0.003). Conclusion: In patients with synchronous CRLM, the surgical strategy should be decided according to the hepatic tumor burden. In the presence of multiple bilobar CRLM, the liver-first approach is associated with longer survival than the alternative approaches and should be evaluated as standard