Metachronous Peritoneal Carcinomatosis Research Articles

The safety and effectiveness of prophylactic hyperthermic intraperitoneal chemotherapy in patients with pathological T3-4 locally advanced colon cancer

The safety and effectiveness of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) in pathological T3-4 locally advanced (pT3N+M0 and pT4NxM0) colon cancer (CC) patients with radical resection need further study. Clinical and pathological information of pT3-4 locally advanced CC patients who received radical surgery in our hospital from January 2018 to December 2020 were analyzed. The prognosis of patients was estimated using Cox proportional hazards regression analysis and Kaplan-Meier method. Among 927 patients, 10.4% (96/927) received prophylactic HIPEC based on 5-FU, 4.6% (43/927) received prophylactic HIPEC based on lobaplatin, 85.0% (788/927) received conventional therapy. The incidence of metachronous peritoneal carcinomatosis (mPC) was 9.4%. Complications occurred in 32 patients (4.1%) in the conventional therapy group, 6 patients (6.3%) in the prophylactic HIPEC group based on 5-FU and 3 patients (7.0%) in the prophylactic HIPEC group based on lobaplatin within 30 days after surgery (5-FU vs. conventional therapy group, p=0.464; Lobaplatin vs. conventional therapy group, p=0.591). Multivariate Cox regression analysis revealed that prophylactic HIPEC based on either 5-FU or lobaplatin regimen could not effectively improve mPC-free survival (5-FU: p=0.020, HR=1.927, 95% CI, 1.111-3.343; Lobaplatin: p=0.167, HR=0.247, 95% CI, 0.034-1.796), overall survival (5-FU: p=0.361, HR=1.360, 95% CI, 0.703-2.634; Lobaplatin: p=0.780, HR=0.816, 95% CI, 0.195-3.416) and disease-free survival (5-FU: p=0.525, HR=1.149, 95% CI, 0.749-1.760; Lobaplatin: p=0.117, HR=0.488, 95% CI, 0.199-1.198). Early prophylactic HIPEC based on 5-FU or lobaplatin subsequent to radical resection for patients with pT3-4 locally advanced CC is safe, but not effective in reducing the risk for mPC.

Reply to Comment on "Risk factors for metachronous peritoneal carcinomatosis after radical resection for patients with nonmetastatic pT3-4 colon cancer".

Reply to Comment on "Risk factors for metachronous peritoneal carcinomatosis after radical resection for patients with nonmetastatic pT3-4 colon cancer".

Risk factors for metachronous peritoneal carcinomatosis after radical resection for patients with nonmetastatic pT3-4 colon cancer.

Patients with nonmetastatic pT3-4 colon cancers are prone to develop metachronous peritoneal carcinomatosis (mPC). Risk factors for mPC and the influence of mutant kirsten rat sarcoma viral oncogene (KRAS)/neuroblastoma rat sarcoma (NRAS)/v-raf murine sarcoma viral oncogene homolog B1 (BRAF) and DNA mismatch repair (MMR) status on mPC remain to be described in these patients. All enrolled patients were identified from the prospectively collected colorectal cancer database of a tertiary referral hospital between 2013 and 2018. Multivariate analysis was used to identify risk factors associated with mPC. Of the 1689 patients with nonmetastatic pT3-4 colon carcinoma, 8.4% (142/1689) progressed to mPC. Endoscopic obstruction (HR = 3.044, p < 0.001), elevated CA125 (HR = 1.795, p = 0.009), pT (T4a vs. T3, HR = 2.745, p < 0.001; T4b vs. T3, HR = 3.167, p = 0.001), pN (N1 vs. N0, HR = 2.592, p < 0.001; N2 vs. N0, HR = 4.049, p < 0.001), less than 12 lymph nodes harvested (HR = 2.588, p < 0.001), mucinous or signet ring cell carcinoma (HR = 1.648, p = 0.038), perineural invasion (HR = 1.984, p < 0.001), and adjuvant chemotherapy (HR = 1.522, p = 0.039) were strongly related to mPC but that mutant KRAS/NRAS/BRAF and MMR status was not associated with mPC. This study identified the high-risk factors for mPC in patients with nonmetastatic pT3-4 colon carcinoma, and these factors should be considered in selective preventive therapy and close follow-up for patients subsequently deemed to have high risk for mPC.

Development of the PERI-Gastric (PEritoneal Recurrence Index) and PERI-Gram (Peritoneal Recurrence Index NomoGRAM) for predicting the risk of metachronous peritoneal carcinomatosis after gastrectomy with curative intent for gastric cancer.

A model that quantifies the risk of peritoneal recurrence would be a useful tool for improving decision-making in patients undergoing curative-aim gastrectomy for gastric cancer (GC). Five Italian centers participated in this study. Two risk scores were created according to the two most widely used pathologic classifications of GC (the Lauren classification and the presence of signet-ring-cell features). The risk scores (the PERI-Gastric 1 and 2) were based on the results of multivariable logistic regressions and presented as nomograms (the PERI-Gram 1 and 2). Discrimination was assessed with the area under the curve (AUC) of receiver operating curves. Calibration graphs were constructed by plotting the actual versus the predicted rate of peritoneal recurrence. Internal validation was performed with a bootstrap resampling method (1000 iterations). The models were developed based on a population of 645 patients (selected from 1580 patients treated from 1998 to 2018). In the PERI-Gastric 1, significant variables were linitis plastica, stump GC, pT3-4, pN2-3 and the Lauren diffuse histotype, while in the PERI-Gastric 2, significant variables were linitis plastica, stump GC, pT3-4, pN2-3 and the presence of signet-ring cells. The AUC was 0,828 (0.778-0.877) for the PERI-Gastric 1 and 0,805 (0.755-0.855) for the PERI-Gastric 2. After bootstrap resampling, the PERI-Gastric 1 had a mean AUC of 0.775 (0.721-0.830) and a 95%CI estimate for the calibration slope of 0.852-1.505 and the PERI-Gastric 2 a mean AUC of 0.749 (0.693-0.805) and a 95%CI estimate for the slope of 0.777-1.351. The models are available at www.perigastric.org . We developed the PERI-Gastric and the PERI-Gram as instruments to determine the risk of peritoneal recurrence after curative-aim gastrectomy. These models could direct the administration of prophylactic intraperitoneal treatments.

Effectiveness of Carbon Ion Radiation in Locally Advanced Pancreatic Cancer.

PurposeEffective treatment strategies for unresectable locally advanced pancreatic cancer (LAPC) patients are eagerly warranted. Recently, convincing oncological outcomes were demonstrated by carbon ion radiotherapy. Nevertheless, there is a lack of evidence for this modern radiation technique due to the limited number of carbon ion facilities worldwide. Here, we analyze feasibility and efficacy of carbon ion radiotherapy in the management of LAPC at Heidelberg Ion Beam Therapy Center (HIT).MethodsBetween 2015 and 2020, 21 LAPC patients were irradiated with carbon ions with a total dose of 48 Gy (RBE) in single doses of 4 Gy (RBE). Three patients (14%) were treated with concomitant chemotherapy with gemcitabine 300 mg/m2 body surface weekly. Toxicity rates were extracted from the charts. Overall survival, progression free survival, local control, and locoregional control were evaluated using Kaplan–Meier estimates.ResultsOne patient developed ascites CTCAE grade III during radiotherapy, which was related to a later histologically confirmed metachronous peritoneal carcinomatosis. No further higher-graded toxicity could be observed. The most common symptoms were nausea and abdominal pain. After a median estimated follow-up time of 19.1 months, the median progression free survival was 3.7 months, and the median overall survival was 11.9 months. The estimated 1-year local control and locoregional control rates were 89 and 84%, respectively.ConclusionCarbon ion radiotherapy of LAPC patients is safely feasible. Local tumor control rates were high. Nevertheless, compared to historical data, an overall survival improvement could not be observed. This could be explained by the poor prognosis of the selected underlying patients that mostly did not respond to prior chemotherapy as well as the early and frequent emergence of distant metastases that demonstrate the necessity of additional chemotherapy in further studies.

A Prediction Model for Metachronous Peritoneal Carcinomatosis in Patients with Stage T4 Colon Cancer after Curative Resection.

Simple SummaryMetachronous peritoneal carcinomatosis (mPC) has a significantly worse overall survival than other metastases in colorectal cancer. Exploring the peritoneal cavity is the only effective way to detect early-stage mPC lesions for curative treatment. The operation cannot be justified in all patients but is possible in patients with higher mPC risk. pT1–3 have a significantly lower risk of developing mPC than pT4. Therefore, we focused on analyzing patients with pT4 colon cancer without distant metastasis, developed a prediction model and used data-driven analysis to select patients with a high risk of developing mPC.(1) Background: The aim of this study was to develop a prediction model for assessing individual mPC risk in patients with pT4 colon cancer. Methods: A total of 2003 patients with pT4 colon cancer undergoing R0 resection were categorized into the training or testing set. Based on the training set, 2044 Cox prediction models were developed. Next, models with the maximal C-index and minimal prediction error were selected. The final model was then validated based on the testing set using a time-dependent area under the curve and Brier score, and a scoring system was developed. Patients were stratified into the high- or low-risk group by their risk score, with the cut-off points determined by a classification and regression tree (CART). (2) Results: The five candidate predictors were tumor location, preoperative carcinoembryonic antigen value, histologic type, T stage and nodal stage. Based on the CART, patients were categorized into the low-risk or high-risk groups. The model has high predictive accuracy (prediction error ≤5%) and good discrimination ability (area under the curve >0.7). (3) Conclusions: The prediction model quantifies individual risk and is feasible for selecting patients with pT4 colon cancer who are at high risk of developing mPC.

Risk factors of metachronous peritoneal carcinomatosis after potentially curative gastric cancer resection in the CRITICS trial.

4053 Background: Peritoneal carcinomatosis (PC) is accountable for over 50% of metastatic spread in gastric cancer (GC). Little is known about factors contributing to the risk of metachronous PC as a single site of metastases after preoperative chemotherapy and potentially curative resection. An accurate prediction model of risk factors identifying high risk populations may pave the way for new treatment strategies, such as intraperitoneal chemotherapy. In this analysis, risk factors for the development of isolated metachronous PC after preoperative chemotherapy and surgical resection were investigated. Methods: In the CRITICS trial, 788 patients with resectable GC were randomized for preoperative chemotherapy and gastrectomy followed by either chemotherapy or chemoradiotherapy. Patients who underwent a potentially curative resection without peritoneal metastases at time of surgery were included in this analysis. Univariate and multivariate analyses were performed using a competing risk model. Results: In total, 617 patients met the inclusion criteria. Overall, 97 of 617 (16%) patients developed metachronous PC. The peritoneum was the first site of recurrence in 64 of 617 (10%) patients. Diffuse or mixed type GC, ypT4 stage and ypN3 stage or a lymph node ratio (LNR) with &gt;20% tumor positivity were independent predictors of isolated PC in both univariate and multivariate analyses with hazard ratios (HR) of 2.90, 2.63 and 2.31, respectively (Table). ypT4 and ypN3 stage or a LNR &gt;20% were also independent predictors of distant recurrence or death with HR of 1.46 and 2.34, respectively. Patients in whom all predictors were present had the highest 2 year cumulative incidences of both isolated PC development and other events of 39.6% and 48.8%, respectively. Conclusions: Diffuse or mixed tumor type, ypT4 and ypN3 or a LNR &gt;20% were identified as independent risk factors for metachronous PC as a single site of metastases in a large cohort of patients treated with preoperative chemotherapy followed by surgical resection. The combination of these factors might identify a subgroup that could benefit from preventive treatment strategies.[Table: see text]

Novel prognostic score for outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal cancer with metachronous peritoneal carcinomatosis.

This study aimed to determine pre- and peri-operative parameters with significant predictive value for post-operative outcomes in patients with recurrent colorectal cancer presenting as peritoneal carcinomatosis undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), and to develop a novel prognostic scoring system for prediction of survival outcomes. A single-institution review of prospectively collected data from all patients who underwent CRS-HIPEC between October 2005 and October 2017 was conducted. Univariate and multivariate analyses were used to identify significant parameters for prediction of post-CRS-HIPEC disease-free survival and overall survival (OS). A total of 278 patients underwent CRS-HIPEC, of whom 72 were for peritoneal carcinomatosis from recurrent colorectal cancer. Disease-free interval (DFI; P = 0.006), peritoneal cancer index (PCI; P = 0.001) and left upper quadrant disease (P = 0.023) were significant independent predictors of 3-year OS. DFI (0.007), PCI (P < 0.001) and intraoperative blood loss (BL; P = 0.001) were significant independent predictors of 5-year OS. PCI and BL were significant independent predictors of both 3-year (P = 0.026, PCI; P = 0.009, BL) and 5-year (P = 0.002, PCI; P = 0.011, BL) disease-free survival. Predictive models were developed for risk stratification of OS. PCI, DFI, left upper quadrant disease and BL have significant predictive value for post-CRS-HIPEC outcomes. Risk stratification models allow for more prudent patient selection and ultimately more accurate prognostication of post-operative outcomes.

Prophylactic HIPEC in pT4 Colon Tumors: Proactive Approach or Overtreatment?

BackgroundThe peritoneum is the second most common site for metastasis in patients with colorectal cancer. Various factors have been studied to identify patients at risk of developing peritoneal carcinomatosis (PC), including T4 tumors. The objectives were to assess the incidence of synchronous and metachronous PC, explore potential risk factors for developing PC as the only site of metastasis, and identify which patients might be candidates for prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC).MethodsWe conducted a retrospective analysis of 125 patients with pT4 colon cancer who underwent surgery in a single center between January 2010 and December 2014.ResultsOf the 947 colon cancer patients who underwent surgery, 125 (13.2%) were diagnosed with pT4a or b colon carcinoma. The median follow-up was 3.7 years. The overall rate of PC was 34.3%, being synchronous in 12% and metachronous in 22.3% of cases. The 8% and 6% of synchronous and metachronous cases of PC respectively were isolated (single site) metastasis. The incidence of PC was 6.1% at 1 year and 14.5% at 3 years after surgery. pT4 was not found to be an independent risk factor for the development of PC (p = 0.231). Nonetheless, the rate of metachronous PC as a single site of metastasis was higher in patients with pT4 tumors and peritoneal nodules around the primary tumor and/or tumor perforation (p = 0.027) and/or who underwent emergency surgery (p = 0.043) than other patients.ConclusionsConsidering pT4 tumor stage as the only risk factor for the development of PC in deciding whether to administer prophylactic HIPEC would lead to unjustified overtreatment.

Peritoneal carcinomatosis in non-small-cell lung cancer: retrospective multicentric analysis and literature review.

We investigated outcomes in patients with advanced non-small-cell lung cancer (NSCLC) and peritoneal involvement. NSCLC patients with peritoneal carcinomatosis (PC) were included. We evaluated mOS1 (overall survival [OS] from NSCLC diagnosis) and mOS2 (OS from diagnosis of PC). In total, 60 NSCLC patients were diagnosed with PC, 12 (20%) patients had a diagnosis of NSCLC and synchronous PC with a median OS of 9months. Smokers had a shorter mOS1 and mOS2 compared with never-smokers; EGFR-mutated patients on tyrosine kinase inhibitors had longer mOS1 and mOS2 than EGFR wild-type patients. Metachronous PC is correlated to a short survival, irrespective of treatment line. Never-smokers and EGFR-mutated patients had improved mOS1 and mOS2 when compared with smokers and EGFR wild-type population.

Peritoneal carcinomatosis after risk-reducing surgery in BRCA1/2 mutation carriers.

Risk-reducing salpingo-oophorectomy (RRSO) is recommended for BRCA1/2 mutation carriers because of their increased risk of ovarian carcinoma. Despite RRSO, metachronous peritoneal carcinomatosis occasionally is diagnosed. The literature was searched for BRCA1/2 mutation carriers with peritoneal carcinomatosis after risk-reducing surgery. The authors were asked for additional data. Clinical and histopathological data were descriptively analyzed. Cases were compared with a single-institution control cohort. Of 36 cases, 86.1% concerned BRCA1 mutation carriers. The median age of the patients was 52 years (range, 30-71 years) at the time of risk-reducing surgery and 60 years (range, 37-75 years) at the time of diagnosis of peritoneal carcinomatosis. The median interval between the 2 events was 54.5 months (range, 11-292 months). Peritoneal carcinomatosis was mostly high-grade serous carcinoma. Histopathological details of the RRSO specimens were retrieved in 8 cases; 5 (62.5%) were found to have serous tubal intraepithelial carcinoma and 1 had epithelial atypia. Cases were older (P = .025) at the time of risk-reducing surgery and harbored more serous tubal intraepithelial carcinomas (P<.001) compared with women from the control cohort. Metachronous peritoneal carcinomatosis after risk-reducing surgery occurs predominantly in BRCA1 mutation carriers, usually within 5 years. Data have suggested that surgery at a younger age lowers the rates of peritoneal carcinomatosis. These data can be used in the gynecologic counseling of BRCA1/2 mutation carriers. RRSO should include complete salpingectomy. Detailed histopathological examination of specimens removed during RRSO is essential. Cancer 2018;124:952-9. © 2018 American Cancer Society.

Overall and disease-free survival in patients treated with CRS + HIPEC with cisplatin and paclitaxel for gastric cancer with peritoneal carcinomatosis

Our experience regarding cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) was reviewed in terms of overall survival (OS) and disease-free survival (DFS) in patients with synchronous peritoneal carcinomatosis (SPC) and metachronous peritoneal carcinomatosis (MPC) from gastric cancer (GC). An analysis of prospectively collected data about patients who underwent CRS and HIPEC from July 2011 to July 2016 was carried out. Patients and tumor characteristics were taken into consideration together with pre and post-operative data. The outcomes concerned OS and DFS in both groups. A total of 17 cases were reported. All patients of SPC group underwent neoadjuvant chemotherapy, while all patients of MPC group underwent adjuvant chemotherapy subsequently to surgery of the primary tumor. The mean follow up period was 9 months (SD±9.5). Thirteen patients (76.5%) had SPC and four (23.5%) had MPC. The mean total Peritoneal Cancer Index (PCI) was 8.5 (SD±8.4). The mean PCI was 3.75 (SD±4.9) for SPC group and 16 (SD±9.5) for MPC (P=0.003). HIPEC regimen was cisplatin plus paclitaxel for fourteen patients (82.4%) and cisplatin plus mitomycin-C (MMC) for three patients (17.6%). OS was 16 months and 6 months respectively in patients with SPC and MPC (P=0.189). DFS was 11 months and 2 months respectively in the two groups (P=0.156). Patients with SPC patients and PCI ≥12 were significantly different in terms of DFS from SPC with PCI <12 (P=0.001). Overall, twelve patients had postoperative major complications (CTCAE>2), in particular eight (61%) in SPC group while four (100%) in MPC group. Our study showed significantly better DFS for patients aged >60 years (P=0.016). HIPEC and CRS with cisplatin and paclitaxel in patients with PC from GC showed promising results in improving the DFS and the OS, particularly for patients with PCI <12 and for those aged >60. Although a high incidence of complications was revealed, especially in MPC group.

Reduction of carcinomatosis risk using icodextrin as a carrier solution of intraperitoneal oxaliplatin chemotherapy

There is no standard treatment in patients with high risk metachronous peritoneal carcinomatosis (PC) in colonic cancer, as perforated tumour or synchronous ovarian metastasis. Icodextrin 4% (ICDX), presently used to prevent postoperative abdominal adhesions, could inhibit the coactivation of the tumour cells and the microenvironment cells, associated with the development of PC. The aim of this study was to inhibit the formation of the PC in a murine model mimicking surgical situation using ICDX and intraperitoneal (IP) prophylactic chemotherapy.We created a model of growing PC in mice using cells of murine colonic cancer CT26. Cells and treatments were injected simultaneously. Five groups were created: CT26 (control group), CT26 + ICDX (ICDX group), CT26 + chemotherapy (oxaliplatin and 5FU) (chemo group), CT26 + chemotherapy + ICDX (ICDX chemo group), ICDX (toxicity group). At day 15, PC was evaluated with rodents PCI.In the chemo group, PCI was significantly lower than in the control group (3.2 versus 8.4, p = 0.02). ICDX had a synergetic effect on PC with chemotherapy; indeed PCI in ICDX chemo group was lower than in chemo group (1.4 versus 3.2, p = 0.04). There was no morbidity linked to ICDX in toxicity group.Safety of ICDX needs to be verified, particularly on colonic anastomosis before ICDX associated to IP chemotherapy could be used as a preventive treatment of PC in high risk patients. This prophylactic treatment is easy to use and would be administrated at the end of a curative surgery for a colonic cancer.

Hipec in the management of metachronous peritoneal carcinomatosis: A single-center retrospective analysis

Hipec in the management of metachronous peritoneal carcinomatosis: A single-center retrospective analysis

External validation of models predicting the individual risk of metachronous peritoneal carcinomatosis from colon and rectal cancer.

To externally validate previously published predictive models of the risk of developing metachronous peritoneal carcinomatosis (PC) after resection of nonmetastatic colon or rectal cancer and to update the predictive model for colon cancer by adding new prognostic predictors. Data from all patients with Stage I-III colorectal cancer identified from a population-based database in Stockholm between 2008 and 2010 were used. We assessed the concordance between the predicted and observed probabilities of PC and utilized proportional-hazard regression to update the predictive model for colon cancer. When applied to the new validation dataset (n=2011), the colon and rectal cancer risk-score models predicted metachronous PC with a concordance index of 79% and 67%, respectively. After adding the subclasses of pT3 and pT4 stage and mucinous tumour to the colon cancer model, the concordance index increased to 82%. In validation of external and recent cohorts, the predictive accuracy was strong in colon cancer and moderate in rectal cancer patients. The model can be used to identify high-risk patients for planned second-look laparoscopy/laparotomy for possible subsequent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Systemic treatment of patients with metachronous peritoneal carcinomatosis of colorectal origin.

Combining chemotherapy and targeted therapies has resulted in an enhanced survival in metastatic colorectal cancer (mCRC) patients. However, the result of this palliative treatment in patients with metachronous peritoneal carcinomatosis (PC) remains unknown. The current population-based study aims to investigate the use and effect of palliative systemic treatment in patients with metachronous PC of colorectal origin. Data on metachronous PC were collected between 2010 and 2011 for all patients who were diagnosed with M0 colorectal cancer between 2003 and 2008 in the Dutch Eindhoven Cancer Registry. Patient demographics and detailed data on chemotherapeutic treatment were collected and compared. Ninety-two patients with metachronous PC received chemotherapy in a palliative setting compared to 94 patients without treatment. In 36 patients, Bevacizumab was added to the treatment (39%). Overall survival was 3.4, 13, and 20.3 months in the no treatment, systemic treatment and systemic treatment + Bevacizumab respectively (P < 0.001). Male gender was a positive predictor and right sided primary tumor location a negative predictor of receiving bevacizumab. Approximately 40% of patients with metachronous PC received bevacizumab in addition to chemotherapy. Treatment with systemic chemotherapy in combination with bevacizumab may increase survival in a patients with metachronous colorectal PC.

Epidemiology, Management, and Survival of Peritoneal Carcinomatosis from Colorectal Cancer: A Population-Based Study.

Modern chemotherapy aims to improve long-term survival for selected patients with peritoneal carcinomatosis. Publications suggest promising results, but the spread of these new aggressive treatment strategies in the general population is not well known. The aim of this study was to draw a picture of epidemiology, management, and survival in synchronous and metachronous peritoneal carcinomatosis from colorectal cancer. The cumulative risk of metachronous peritoneal carcinomatosis was estimated in patients resected for cure. Net survival rates were calculated for synchronous and metachronous peritoneal carcinomatosis. The study was conducted with the use of the Burgundy Digestive Cancer Registry. Overall, 9174 primary colorectal cancers registered between 1976 and 2011 by the population-based digestive cancer registry were considered. In total, 7% of patients were diagnosed with synchronous peritoneal carcinomatosis. The 5-year cumulative risk of metachronous peritoneal carcinomatosis was 6%, and the stage of the colorectal cancer at diagnosis was the major risk factor. Other independent risk factors were mucinous adenocarcinoma, ulceroinfiltrating tumors, and diagnosis after obstruction or perforation. The proportion of patients resected for cure was 11% and 9% for synchronous and metachronous peritoneal carcinomatosis, and 3-year overall net survival was 8% and 5%. The corresponding rates after resection for cure were 21% and 17%. There was a dramatic increase in the proportion of patients receiving systemic chemotherapy: from 11% before 1997 to 48% in 2011 for synchronous peritoneal carcinomatosis and from 3% to 38% for metachronous peritoneal carcinomatosis. This is a retrospective observational population-based study. Peritoneal carcinomatosis complicating colorectal cancer is a major reason for treatment failure. This study identified patients at a high risk of developing peritoneal carcinomatosis who may benefit from specific surveillance. New therapeutic modalities are also needed to improve the prognosis.

Incidence, time course and independent risk factors for metachronous peritoneal carcinomatosis of gastric origin--a longitudinal experience from a prospectively collected database of 1108 patients.

BackgroundComprehensive evidence on the incidence, time course and independent risk factors of metachronous peritoneal carcinomatosis (metaPC) in gastric cancer patients treated with curative intent in the context of available systemic combination chemotherapies is lacking.MethodsData from a prospectively collected single-institutional Center Cancer Registry with 1108 consecutive patients with gastric adenocarcinoma (GC), clinical, histological and survival data were analyzed for independent risk factors and prognosis with focus on the development of metaPC. Findings were then stratified to the time periods of treatment with surgery alone, 5-Fluorouracil-only and contemporary combined systemic perioperative chemotherapy strategies, respectively.ResultsDespite R0 D2 gastrectomy (n = 560), 49.6% (±5.4%) of the patients were diagnosed with tumour recurrence and 15.5% (±1.8%) developed metaPC after a median time of 17.7 (15.1-20.3) months after surgery resulting in a tumour related mortality of 100% with a median survival of 3.0 months (2.1 – 4.0). Independent risk factors for the development of metaPC were serosa positive T-category, nodal positive-status, signet cell and undifferentiated gradings (G3/G4). Contemporary systemic combination chemotherapy did not improve the incidence and prognosis of metaPC (p = 0.54).ConclusionsDespite significant improvements in the overall survival for the complete cohort with gastric cancer over time, those patients with metaPC did not experience the same benefits. The lack of change in the incidence, and persistent poor prognosis of metaPC after curative surgery expose the need for further prevention and/or improved treatment options for this devastating condition.

Individualized prediction of risk of metachronous peritoneal carcinomatosis from colorectal cancer

The purpose of the study was to develop a tool for predicting the individual risk of metachronous peritoneal carcinomatosis after surgery for non-metastatic colorectal cancer. Independent predictors for metachronous colorectal carcinomatosis have previously been identified using a population-based database. Predictive models for colon and rectal cancer were developed from these data. The predictive models were based on multivariable Cox proportional hazard regression and were internally validated with bootstrapping. Performance was assessed by the concordance index and calibration plots. In all, 8044 patients who underwent abdominal resection of colorectal cancer Stage I-III were included. The colon and rectal cancer risk score models predicted metachronous peritoneal carcinomatosis with a concordance index of 80% and 78%, respectively. Factors in the models included age, pathological pT stage, pN stage, number of examined lymph nodes (0-11, 12+), type of surgery (emergency/elective), completeness of cancer resection (R0/R1/R2), adjuvant chemotherapy (yes/no), preoperative radiotherapy and tumour location. The proposed predictive models showed high internal validity and enabled individualized prediction of peritoneal recurrence of colorectal cancer. The models may help in the planning of treatment and follow-up of patients. However, external validation is warranted to assess generalizability of the predicted absolute risks.

Hyperthermic intraperitoneal chemoperfusion in combined treatment of locally advanced and disseminated gastric cancer: Results of a single-centre retrospective study

Background: Patients with locally advanced gastric cancer (GC) and/or peritoneal metastases have a poor prognosis despite systemic chemotherapy or palliative surgery. The aim of this retrospective comparative non-randomised study was to evaluate aggressive cytoreduction in combination with hyperthermic intraperitoneal chemoperfusion (HIPEC) as a novel treatment strategy for patients with intraperitoneal disseminated and locally advanced GC.Patients and methods: Forty-nine GC patients with serosal invasion (n = 19), limited peritoneal metastases (n = 20), or disseminated peritoneal metastases and tense ascites (n = 10) underwent combination therapy with HIPEC. Three matched control groups undergoing standard therapies were retrospectively identified.Results: Combination therapy for serosa-invasive GC reduced the level of metachronous peritoneal carcinomatosis and increased median survival from 12 months to 22.5 months (p = 0.001). The median and 1-year survival rates for intraperitoneal disseminated GC patients undergoing therapy with the use of HIPEC were 12 months and 68.8% compared with 8 months and 25%, respectively (p = 0.004) for control subgroup patients (palliative chemotherapy). The symptomatic use of HIPEC allows effective elimination of recurrent ascites in GC patients.Conclusion: HIPEC is a well-tolerated and effective method of adjuvant therapy for gastric cancer with high risk of intraperitoneal progression. Cytoreduction followed by HIPEC improves survival in patients with limited peritoneal carcinomatosis of gastric origin.