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Percutaneous lung ablation of pulmonary recurrence may improve survival in selected patients undergoing cytoreductive surgery for colorectal cancer with peritoneal carcinomatosis
Abstract
Purpose:
To analyze the outcomes of patients developing pulmonary metastases (PM) following cytoreductive surgery (CRS) and perioperative intra-peritoneal chemotherapy (IPC) for colorectal cancer (CRC) with peritoneal carcinomatosis.
Patients and methods:
A retrospective analysis of patients undergoing CRS/IPC for CRC from 1996 to 2016 was performed. Lung-specific disease-free and patient overall survival was analyzed. Patients undergoing percutaneous lung ablative therapy (PLAT) for PM were compared to patients receiving systemic chemotherapy alone.
Results:
273 patients underwent CRS/IPC for CRC. Of these, 61 (22%) developed PM. Median time to development of PM was 8 months (range 0-52 months) and 41 patients (67%) had metachronous lesions. Twenty-one PM patients underwent PLAT, either by radio-frequency or micro-wave ablation, for an average of 3 lesions (range 1-12) and 13 (62%) had bilobar disease. The most common post-interventional complication was the development of pneumothorax (71%). Overall survival following development of PM was 18 months and higher in patients undergoing PLAT compared to those treated with systemic chemotherapy (26 vs. 14 months, p = 0.03). In eight cases (38%) local tumor recurrence developed post-PLAT. A peritoneal carcinomatosis index >10 (HR 3.48, 95% CI 1.69-7.19), presence of liver metastases (HR 2.49, 95% CI 1.24-5.03) and PLAT (HR 0.43, 95% CI 0.20-0.93) were identified as significant predictors of overall survival following diagnosis of PM.
Conclusion:
PM develop in approximately a fourth of patients undergoing CRS/IPC for CRC. Of these, about 1/3 may be eligible for PLAT. PLAT is a valuable treatment option providing good local control and potentially prolongation of overall survival.
... 9,10 Although a few studies have begun to investigate the impact of CRS-HIPEC with combined resection of EPD on OS and recurrence-free survival (RFS), the role of CRS-HIPEC in the setting of EPD remains poorly understood. [11][12][13][14] Therefore, we sought to assess the prognostic impact of EPD on patients undergoing CRS-HIPEC for AC or CRC in an effort to improve patient selection for CRS-HIPEC. ...
... One study showed acceptable outcomes of CRS-HIPEC for CRC with PM and pulmonary metastases, especially when combined with percutaneous ablation of the lung metastases. 11 Interestingly, our study found that isolated lung or RP LN metastases were the most common sites of EPD among patients undergoing CRS-HIPEC, which contrasts from Baratti et al., where patients' EPD was predominantly in the liver. 24 This study is one of the first to report outcomes in patients with RP LN metastases and one of few to report outcomes in patients with pulmonary metastases. ...
Introduction
The role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with extraperitoneal disease (EPD) is controversial.
Methods
Among patients with peritoneal metastases from appendiceal cancer (AC) and colorectal cancer (CRC) who underwent CRS-HIPEC, those with EPD (liver, lung, or retroperitoneal lymph nodes [RP LN]) were retrospectively compared to those without EPD. Overall (OS) and recurrence-free survival (RFS) analyses were performed before/after propensity score matching (PSM).
Results
Among 1341 patients with AC (64%) or CRC (36%) who underwent CRS ± HIPEC, 134 (10%) had EPD whereas 1207 (90%) did not. EPD was located in the lungs (47%), RP LN (28%), liver (18%), or multiple (6%). Patients with EPD experienced worse median OS (34 versus 63 mo; P = 0.002) and RFS (12 versus 19 mo; P < 0.001). On a multivariable analysis, EPD was associated with worse RFS (P = 0.003), but not OS (P = 0.071). After PSM, the association of EPD with OS (P = 0.204) and RFS (P = 0.056) was no longer significant. In the multivariable analysis of the PSM cohort, EPD was not associated with OS (P = 0.157) or RFS (P = 0.110).
Conclusions
The findings of this large retrospective multi-institutional study suggest that EPD alone, while a negative prognostic indicator, should not be considered an absolute contraindication to CRS ± HIPEC for otherwise well-selected patients with peritoneal surface malignancies. Further research is needed to delineate whether location of EPD influences OS and RFS following CRS-HIPEC.
... Thermal ablation has minimal effects on pulmonary function or QoL, can be repeated, and may be considered more acceptable to patients because of the associated short stay in hospital and fast recovery [16]. Traiki and colleagues suggested that RPM in patients with colorectal cancer could be treated by percutaneous ra- diofrequency/microwave ablation to provide good local control and potentially prolongation of overall survival; however, the incidence of pneumothorax was significantly higher (71%) than that of this group [17]. ...
Purpose:
The aim of the study was to determine how many times iodine-125 (125I) seed brachytherapy (ISB) for recurrent pulmonary metastases (RPM) can be done, and the clinical efficacy and complications of repeated ISB in RPM treatment.
Material and methods:
Between September 2013 and August 2018, 18 patients with RPM, after conventional chemotherapy, radiotherapy, and trans-arterial chemoembolization, received CT-guided repeated ISB. Patients were followed up, and local control, survival, and post-operative complications were analyzed retrospectively. The Kaplan-Meier method was used for survival analyses.
Results:
Eighty-two metastases in 18 patients were treated with ISB, with 71 implantations (mean number of implantations per patient, 4; range, 3-8). The total number of implanted 125I seeds was 1,220 (mean number per patient, 68; minimum, 40; maximum, 110). The mean value of D90 for ISB was 138 Gy. Local control was 91.46%, 90.24%, and 89.02% at 1, 3, and 6 months after ISB, respectively. After repeated ISB, good local control was achieved, and all patients were discharged from hospital within 3 days. One month after, six metastases of large diameter were treated with ISB; computed tomography revealed level 1 radioactive injury to the lungs, but special treatment was not administered. Post-operative renal, hepatic, and vascular functions were normal.
Conclusions:
ISB for RPM is safe and efficacious. RPM treatment seems not to be limited by number of times ISB could be repeated; at least up to 8 times for different sites of lung.
Purpose
To retrospectively evaluate the safety and efficacy of percutaneous computed tomography (CT)-guided microwave ablation (MWA) in colorectal cancer (CRC) lung metastases, and to analyze prognostic factors.
Materials and methods
Data were collected from 31 patients with CRC lung metastases from May 2013 to September 2017. They had removed the CRC, no extrapulmonary metastases, no more than three metastases in the lung, the maximum diameter of the lesions was ≤3 cm, and all the lung metastases could be completely ablated. The ablation procedures were performed using a KY-2000 microwave multifunctional therapeutic apparatus. Efficacy is assessed two to four weeks after ablation, and follow-up are performed every three months for two years. The primary outcome was overall survival (OS). The secondary outcomes were progression-free survival (PFS), and complications. Cox regression analysis was used for the evaluation of the statistical significance of factors affecting the end result of MWA therapy. The Kaplan–Meier method was used for estimation of survival rates.
Results
A total of 45 metastatic lung lesions from CRC in 31 patients were treated with CT-guided MWA procedures. The median OS was 76 months. The one, two, three, and five-year survival rates were 93.5%, 80.6%, 61.3%, and 51.6%, respectively. Multivariate analysis showed that the primary tumor from the rectum (P = 0.009) and liver metastases at the diagnosis of lung metastases (P = 0.043) were risk factors affecting OS, while PFS was a protective factor. The median PFS was 13 months. The maximum diameter of lung metastases lesions (P = 0.004) was a risk factor. The interval between pulmonary metastases and MWA (P=0.031) was the protective factor. Pneumothorax was observed in 13 out of 36 procedures. Four patients developed pneumothorax requiring drainage tube insertion. No patient deaths occurred within 30 days of ablation. Three out of 31 patients (9.67%) were found to have local recurrence of the original lung metastatic ablation foci.
Conclusion
MWA therapy may be safely and effectively used as a therapeutic tool for the treatment of selected CRC pulmonary metastases, and the prognosis is better in patients without liver metastases at the diagnosis of lung metastases.
Background:
Pulmonary metastasectomy has been widely adopted in the treatment of metastatic disease. In recent years image guided ablation has seen increased use in the treatment of thoracic malignancies. The objective of this study was to evaluate oncological outcomes following percutaneous ablation (PA) of pulmonary metastasis.
Methods:
A comprehensive search of the PubMed, MEDLINE and EMBASE databases from January 2000 to August 2021 was performed to identify studies evaluating patient survival following ablation of lung metastasis. Pooled outcomes have been presented with a random effects model to assess primary outcomes of overall survival, progression free survival and 1-year local control. Secondary outcomes included procedural mortality, major complications, and the incidence of pneumothorax.
Results:
A total of 24 studies were identified. The pooled median overall survival was 5.13 [95% confidence interval (CI): 4.37-6.84] years, and the 1-, 3-, 5-year progression free survival rates were 53%, 26% and 20% respectively. The 1-year local control rate was 91% (95%CI: 86-95%). Periprocedural mortality was rare (0%; 95%CI: 0-1%), as were major complications excluding pneumothorax (1%; 95%CI: 1-2%). Pneumothorax developed in 44% of ablation sessions, although only half of these required chest tube placement. Most patients were able to be discharged day one post-procedurally.
Conclusion:
PA demonstrates high overall, progression free and local tumour survival in patients with lung metastasis. Complications and mortality are also rare. Consideration of its use should be made in a tumour board meeting in conjunction with surgical and radiotherapy perspectives for targeted local control of metastases.
La survenue de métastases péritonéales de cancer colorectal (MPCCR) constitue un facteur péjoratif dans l’évolution du cancer colorectal, plus encore que pour les autres sites métastatiques. Leur traitement repose sur la chirurgie de cytoréduction complète (CRS). Lors de la résection de la tumeur primitive, une exploration péritonéale complète doit être systématiquement réalisée. En cas de découverte peropératoire de MPCCR, la stratégie chirurgicale doit être discutée en fonction de l’expertise locale et de l’étendue des MPCCR. Une CRS d’emblée peut éventuellement être réalisée en cas de MPCCR limitées à la zone péritumorale, sous réserve d’une exploration exhaustive réalisée par laparotomie. Dans les autres cas, le patient devrait être adressé dans un centre expert, et la CRS différée après une chimiothérapie préopératoire. La présence de métastases extrapéritonéales associées aux MPCCR est un facteur pronostique majeur. En cas de métastases hépatiques associées, la réalisation d’une chirurgie combinée est possible si à la fois la maladie péritonéale et la maladie hépatique sont peu étendues ; ce traitement apporte un bénéfice de survie par rapport au traitement systémique, malgré un risque de morbidité postopératoire plus élevé qu’en cas de CRS seule. En cas de métastases pulmonaires associées, un traitement local par thermoablation percutanée peut être envisagé, notamment chez les patients avec une maladie péritonéale limitée et sans métastases hépatiques. Après traitement chirurgical de MPCCR, une majorité de patients (plus de 80 %) présenteront une récidive qui sera exclusivement péritonéale dans un tiers des cas. Une CRS itérative est envisageable chez des patients bien sélectionnés (maladie péritonéale peu étendue, intervalle libre > 12 mois, CRS complète possible), avec des résultats de survie inférieurs à la CRS de première intention, mais meilleurs qu’en cas de chimiothérapie systémique seule.
Introduction:
Over the last 20 years, complete cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) dramatically increased the survival of patients with colorectal peritoneal metastases (CRPM). However, despite better knowledge of the disease, around 70% of patients relapse after CRS with HIPEC. This study was designed to analyse the pattern of recurrence and the outcomes of different treatment modalities.
Methods:
Patients relapsing after CRS plus HIPEC for CRPM were selected from a prospective database. The impact of iterative curative-intent treatments was analysed using Kaplan-Meier estimates and multivariate Cox regression models.
Results:
Between April 1993 and December 2014, 190 of 274 (69%) patients previously treated by CRS plus HIPEC developed relapse, as an isolated peritoneal recurrence (31%), isolated distant recurrence (35%), or multisite recurrence (34%). The curative-intent treatment rate was 48% for isolated peritoneal recurrences, 49% for isolated distant recurrences and 22% for multisite recurrences (p = 0.002). From the diagnosis of relapse, 3- and 5-year overall survival were 77% and 46% after curative-intent treatment and 14% and 4.7% after non-curative treatment, with median survival of 59.7 and 18.3 months (log-rank p < 0.0001), respectively. Regression analysis identified the initial extent of CRPM (hazard ratio [HR]: 2.25; p < 0.0001), iterative curative-intent treatment (HR: 0.22; p < 0.0001) and disease-free interval (HR: 1.77; p = 0.01) as independent predictors of prolonged survival.
Conclusions:
Iterative curative-intent treatment can be performed in up to 40% of patients with relapse after CRS and HIPEC for CRPM, and is associated with prolonged survival in selected patients.
Objectives
To report overall survival and local control for patients identified in the RSSearch® Patient Registry with metastatic cancer to the lung treated with SBRT. Methods
Seven hundred two patients were identified with lung metastases in the RSSearch® Registry. Of these patients, 577 patients had SBRT dose and fractionation information available. Patients were excluded if they received prior surgery, radiation, or radiofrequency ablation to the SBRT treated area. Between April 2004-July 2015, 447 patients treated with SBRT at 30 academic and community-based centers were evaluable for overall survival (OS). Three hundred four patients with 327 lesions were evaluable for local control (LC). All doses were converted to Monte Carlo equivalents and subsequent BED Gy10 for dose response analysis. ResultsMedian age was 69 years (range, 18–93 years). Median Karnofsky performance status (KPS) was 90 (range 25/75% 80–100). 49.2% of patients had prior systemic therapy. Median metastasis volume was 10.58 cc (range 25/75% 3.7–25.54 cc). Site of primary tumor included colorectal (25.7%), lung (16.6%), head and neck (11.4%), breast (9.2%), kidney (8.1%), skin (6.5%) and other (22.1%). Median dose was 50 Gy (range 25/75% 48–54) delivered in 3 fractions (range 25/75% 3–5) with a median BED of 100Gy10 (range 25/75% 81–136).Median OS for the entire group was 26 months, with actuarial 1-, 3-, and 5-year OS of 74.1%, 33.3, and 21.8%, respectively. Patients with head and neck and breast cancers had longer median OS of 37 and 32 months respectively, compared to colorectal (30 months) and lung (26 months) which corresponded to 3-year actuarial OS of 51.8 and 47.9% for head and neck and breast respectively, compared to 35.8% for colorectal and 31.2% for lung.The median LC for all patients was 53 months, with actuarial 1-, 3-, and 5-year LC rates of 80.4, 58.9, and 46.3%, respectively. There was no difference in LC by primary histologic type (p = 0.49). Improved LC was observed for lung metastases that received SBRT doses of BED ≥100Gy10 with 3-year LC rate of 77.1% compared to 45% for lung metastases treated with BED < 100Gy10 (p = 0.01). Smaller tumor volumes (<11 cc) had improved LC compared to tumor volumes > 11 cc. (p = 0.005) Two-year LC rates for tumor volumes < 11 cc, 11–27 cc and > 27 cc were 72.9, 64.2 and 45.6%, respectively. This correlated with improved OS with 2-year OS rates of 62.4, 60.9 and 46.2% for tumor volumes < 11 cc, 11–27 cc and > 27 cc, respectively (p = 0.0023). In a subset of patients who received BED ≥100Gy10, 2-year LC rates for tumor volumes < 11 cc, 11–27 cc and > 27 cc were 82.8, 58.9 and 68.6%, respectively (p = 0.0244), and 2-year OS rates were 66.0, 58.8 and 28.5%, respectively (p = 0.0081). Conclusion
Excellent OS and LC is achievable with SBRT utilizing BED ≥100Gy10 for lung metastases according to the RSSearch® Registry data. Patients with small lung metastases (volumes < 11 cc) had better LC and OS when using SBRT doses of BED ≥100Gy10. Further studies to evaluate a difference, if any, between various tumor types will require a larger number of patients.
Background:
Lung is the second most common site of colorectal cancer metastasis. Treatment is based mainly on systemic therapy which has largely evolved lately, but outcome remains relatively poor. The place of locoregional therapies as curative strategies is still debated.
Method:
A systematic literature review was performed by the authors for systemic therapy, surgery, radiofrequency ablation (RFA), and stereotactic body radiation therapy (SBRT). The highest level of evidence for each strategy was presented. Major findings were addressed in a summarized and clinically relevant manner.
Results:
All reported studies were descriptive non comparative reports except for one retrospective study comparing surgery to SBRT. The highest level of evidence for each therapeutic strategy are presented as follows: three large meta-analyses for surgery as well as seven and three prospective trials for RFA and SBRT, respectively.
Discussion:
Surgery has the highest level of evidence for cure followed by RFA and SBRT. However, careful patient selection and complete resection of all metastasis are the main principles behind the efficacy of local therapies in the curative setting. Despite encouraging results, randomized trials are still needed.
Background
This study aimed to clarify the prognostic significance of tumour markers on long-term survival in colorectal peritoneal carcinomatosis (CRPC) following cytoreductive surgery and intraperitoneal chemotherapy.
Patients and Methods
Preoperative serum tumour markers of 164 patients with CRPC were analyzed. Peritoneal cancer index (PCI) was measured and relationship to survival calculated.
Results
Carcinoembryonic antigen (CEA) >6.5 mg/l and cancer antigen 125 (CA125) >16 U/ml remained independent predictors of survival after adjusting for PCI [adjusted hazard ratio (aHR)=2.46, 95% confidence interval (CI)=1.3-4.5, p<0.01 and aHR=2.23, 95% CI=1.21-4.09, p<0.01, respectively]. Patients with high CEA and low CA125 or vice versa had an approximately triple risk of death (HR=3.34, 95% CI=1.21 9.25, p=0.02 and HR=2.76, 95% CI=1.01 7.77, p=0.04, respectively). High CEA with high CA125 produced an additive effect, reflecting a six-fold increase in death (HR=6.57, 95% CI=2.62 13.69, p<0.001, median survival: not reached vs. 22 months).
Conclusion
Serum CEA and CA125 in patients with CRPC treated with cytoreductive surgery and intraperitoneal chemotherapy convey a negative prognostic effect independently of PCI.
Background:
Cytoreductive peritoneal surgery (CRS) associated with hyperthermic peritoneal chemotherapy (HIPEC) has long been considered the standard treatment for colorectal peritoneal metastases (CPM). However, although efficacy of surgery has been demonstrated, evidence supporting HIPEC's role is less certain.
Method:
Overall survival (OS), progression-free survival (PFS) and morbidity were analysed retrospectively for fifty consecutively included patients treated for colorectal CPM with complete CRS and systemic chemotherapy only.
Results:
Median peritoneal cancer index (PCI) was 8 (range 1-24). 23 patients had liver or lung metastases (LLM). 22 patients had synchronous CPM. 27 complications occurred (12 Grade 1/2, 14 Grade 3, 1 Grade 4a, 0 Grade 5). Median follow-up was 62.5 months (95 %CI 45.4-81.3), median survival 32.4 months (21.5-41.7). Three- and 5-year OS were 45.5% (0.31-0.59) and 29.64% (0.17-0.44) respectively. Presence of LLMs associated with peritoneal carcinomatosis was significantly associated with poorer prognosis, with survival at 5 years of 13.95% (95 %CI 2.9-33.6) vs. 43.87% (22.2-63.7) when no metastases were present (P= 0.018). Median PFS was 9.5 months (95 %CI 6.2-11.1).
Conclusion:
With an equivalent PCI range and despite one of the highest rates of LLM in the literature, our survival data of CRS + systemic chemotherapy only compare well with results reported after additional HIPEC. Tolerance was better with acceptable morbidity without any mortality. Extra-hepatic metastasis (LLM) is a strong factor of poor prognosis. Awaiting the results of the randomized PRODIGE trial, these results indicate that CRS + systemic chemotherapy only is a robust hypothesis to treat colorectal CPM.
Background:
Colorectal cancer peritoneal metastasis (CPM) confers an exceptionally poor prognosis, and traditional treatment involving systemic chemotherapy (SC) is largely ineffective. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly advocated for selected patients with CPM; however, opinions are divided because of the perceived lack of evidence, high morbidity, mortality, and associated costs for this approach. As there is no clear consensus, the aim of this study was to compare outcomes following CRS+HIPEC vs SC alone for CPM using meta-analytical methodology, focusing on survival outcomes. Secondary outcomes assessed included morbidity, mortality, quality of life (QOL), and health economics (HE).
Methods:
An electronic literature search was conducted to identify studies comparing survival following CRS+HIPEC vs SC for CPM. The odds ratio (OR) was calculated using the Mantel-Haenszel method with corresponding 95% confidence intervals (CI) and P-values. Heterogeneity was examined using the Q-statistic and quantified with I(2). The fixed-effect model (FEM) was used in the absence of significant heterogeneity. For included studies, 2- and 5-year survival was compared for CRS+HIPEC vs SC alone.
Results:
Four studies (three case-control, one RCT) provided comparative survival data for patients undergoing CRS+HIPEC (n=187) vs SC (n=155) for CPM. Pooled analysis demonstrated superior 2-year (OR 2.78; 95% CI 1.72-4.51; P=0.001) and 5-year (OR 4.07; 95% CI 2.17-7.64; P=0.001) survival with CRS+HIPEC compared with SC. Mortality ranged from 0 to 8%. No data were available for the assessment of QOL or HE.
Conclusions:
Although limited by between-study heterogeneity, the data support the assertion that in carefully selected patients, multimodal treatment of CPM with CRS+HIPEC has a highly positive prognostic impact on medium- and long-term survival compared with SC alone. There is a paucity of comparative data available on morbidity, QOL, and HE.
Systemic chemotherapy has enabled prolongation of survival in patients with stage IV colorectal cancer. This has subsequently increased the relative significance of local therapy for patients with oligometastases because they can be cured by removal of oligometastatic lesions. One of the most frequently reported tumor histologies for oligometastases is colorectal cancer. Resection is the standard therapy in most settings of oligometastases. Recently, studies have shown that stereotactic body radiotherapy (SBRT) may become a treatment option that provides high local control with minimal morbidity. Two-year local control rates following SBRT for hepatic and pulmonary oligometastases are almost over 80% and are even higher for patients treated with high-dose regimens. The indications of SBRT for other metastatic sites or conditions include isolated lymph nodes, spinal and adrenal metastasis, and post-surgical pelvic recurrence. Many retrospective studies have indicated that SBRT for various lesions results in good outcomes with low morbidity, both in the curative and palliative setting. However, few reports with a high level of evidence have indicated the efficacy of SBRT compared to standard therapy. Hereafter, the optimal indication of SBRT needs to be prospectively investigated to obtain convincing evidence.
Purpose:
Recurrent disease following complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a relevant clinical scenario. We aimed to determine risk factors for recurrence.
Methods:
Prospectively collected data of patients enrolled in the Peritoneal Surface Malignancy Program at the University of Tübingen between 2005 and 2011 were retrospectively analyzed. All patients were treated by standardized CRS and HIPEC. Recurrence was defined either radiographically by CT, PET-CT scan, or reoperation.
Results:
Fifty-two patients received complete CRS (CC-0/CC-1) and HIPEC. Median time to recurrence was 229 days (103-1,028). Overall recurrence rate within follow-up was 48 %. Of patients with recurrent disease, 44 % experienced extraperitoneal systemic tumor spread. In multivariate analysis, grading of ≥ 3 was shown as an independent risk factor for recurrent disease, while a trend was observed for maximal tumor load in the upper abdominal region. Clinical parameters did not show an impact on recurrence.
Conclusions:
Primary tumor grading seems to be an independent risk factor for recurrence following complete CRS and HIPEC in colorectal cancer-derived peritoneal surface malignancies.
Peritoneal carcinomatosis (PC) of colorectal cancer (CRC) is common and is the second most common cause of death. Clinical studies regarding chemotherapy for CRC with PC have been classically rather limited in scope. We evaluated the efficacy of modified oxaliplatin, leucovorin, and fluorouracil (m-FOLFOX4) regimen for PC of CRC origin.
CRC patients with PC were treated with cycles of oxaliplatin at 85 mg/m(2) on day 1, leucovorin 20 mg/m(2) followed by 5-fluorouracil (5-FU) via a 400 mg/m(2) bolus and a 22 hours continuous infusion of 600 mg/m(2) 5-FU on days 1-2 at 2-week intervals.
Forty patients participated in this study. Median age was 55 years. Thirty-two patients (80.0%) received previous operation, and 60.0% of PC occurred synchronously. Thirty-five patients (87.5%) were assessable and exhibited measurable lesions. Two patients (5.7%) demonstrated complete response and five patients (14.3%) showed partial response. The median time to progression was 4.4 months (95% confidence interval, 2.5 to 6.3 months), the median overall survival time was 21.5 months (95% confidence interval, 17.2 to 25.7 months). There was no treatment related death. Presence of liver metastasis (p=0.022), performance status (p=0.039), and carcinoembryonic antigen level (p=0.016) were related to the time to progression. Patients with low carcinoembryonic antigen level (37.2 months vs. 15.6 months, p=0.001) or good performance status (22.5 months vs. 6.8 months, p=0.040) showed better overall survival.
The m-FOLFOX4 regimen was determined to be effective for CRC patients with PC.
Resection of hepatic metastases is indicated in selected stage IV colorectal cancer (CRC) patients. A minority will eventually develop pulmonary metastases and may undergo lung surgery with curative intent. The aims of the present study were to assess clinical outcome and identify parameters predicting survival after pulmonary metastasectomy in patients who underwent prior resection of hepatic CRC metastases.
We performed a retrospective analysis of 27 consecutive patients (median age 62 years; range: 33-75 years) who underwent resection of pulmonary metastases after previous hepatic metastasectomy from CRC in two institutions from 1996 to 2009. All patients underwent complete resection (R0) for both colorectal and hepatic metastases.
Median follow-up was 32 months (range: 3-69 months) after resection of lung metastases and 65 months (range: 19-146 months) after resection of primary CRC. Three- and 5-year overall survival rates after lung surgery were 56 and 39%, respectively, and median survival was 46 months (95% CI 35-57). Median disease-free survival after pulmonary metastasectomy was 13 months (95% CI 5-21). At the time of last follow-up, seven patients (26%) had no evidence of recurrent disease and 6 of these 7 patients presented initially with a single lung metastasis.
Resection of lung metastases from CRC patients may result in prolonged survival, even after previous hepatic metastasectomy. Yet, prolonged disease-free survival remains the exception, and seems to occur only in patients with a single lung lesion.
Symptoms and complications of metastatic colorectal cancer (mCRC) differ by metastatic sites. There is a paucity of prospective survival data for patients with peritoneal carcinomatosis colorectal cancer (pcCRC). We characterized outcomes of patients with pcCRC enrolled onto two prospective randomized trials of chemotherapy and contrasted that with other manifestations of mCRC (non-pcCRC).
A total of 2,095 patients enrolled onto two prospective randomized trials were evaluated for overall survival (OS) and progression-free survival (PFS). A Cox proportional hazard model was used to assess the adjusted associations.
The characteristics of the pcCRC group (n = 364) were similar to those of the non-pcCRC patients in median age (63 v 61 years, P = .23), sex (57% males v 61%, P = .23), and performance status (Eastern Cooperative Oncology Group performance status 0 or 1 94% v 96%, P = .06), but differed in frequency of liver (63% v 82%, P < .001) and lung metastases (27% v 34%, P = .01). Median OS (12.7 v 17.6 months, hazard ratio [HR] = 1.3; 95% CI, 1.2 to 1.5; P < .001) and PFS (5.8 v 7.2 months, HR = 1.2; 95% CI, 1.1 to 1.3; P = .001) were shorter for pcCRC versus non-pcCRC. The unfavorable prognostic influence of pcCRC remained after adjusting for age, PS, liver metastases, and other factors (OS: HR = 1.3, P < .001; PFS: HR = 1.1, P = .02). Infusional fluorouracil, leucovorin, and oxaliplatin was superior to irinotecan, leucovorin, and fluorouracil as a first-line treatment among pcCRC (HR for OS = 0.62, P = .005) and non-pcCRC patients (HR = 0.66, P < .001).
pcCRC is associated with a significantly shorter OS and PFS as compared with other manifestations of mCRC. Future trials for mCRC should consider stratifying on the basis of pcCRC status.
To retrospectively evaluate long-term survival, local tumor progression, and complication rates for all percutaneous computed tomographic (CT)-guided lung tumor radiofrequency (RF) ablations performed at a tertiary care cancer hospital in patients who refused or who were not candidates for surgery.
This HIPAA-compliant study was approved by the institutional review board; informed consent was waived. Between 1998 and 2005, 153 consecutive patients (mean age, 68.5 years; range, 17-94 years) with 189 primary or metastatic medically inoperable lung cancers underwent percutaneous fluoroscopic CT-guided RF ablation. Clinical outcomes were compiled on the basis of review of medical records, imaging follow-up reports, and any biopsy-proved residual or recurrent disease (when available). Kaplan-Meier method was used to estimate overall survival and disease-free survival (progression) as a function of time since RF ablation. Comparisons between survival functions were performed by using the log-rank statistic; P < .05 was considered to indicate a significant difference.
The overall 1-, 2-, 3-, 4-, and 5-year survival rates, respectively, for stage I non-small cell lung cancer were 78%, 57%, 36%, 27%, and 27%; rates for colorectal pulmonary metastasis were 87%, 78%, 57%, 57%, and 57%. The 1-, 2-, 3-, 4-, and 5-year local tumor progression-free rates, respectively, were 83%, 64%, 57%, 47%, and 47% for tumors 3 cm or smaller and 45%, 25%, 25%, 25%, and 25% for tumors larger than 3 cm. The difference between the survival curves associated with large (>3 cm) and small (< or =3 cm) tumors was significant (P < .002). The overall pneumothorax rate was 28.4% (52 of 183 ablation sessions), with a 9.8% (18 of 183 ablation sessions) chest tube insertion rate. The overall 30-day mortality rate was 3.9% (six of 153 patients), with a 2.6% (four of 153 patients) procedure-specific 30-day mortality rate.
Lung RF ablation appears to be safe and linked with promising long-term survival and local tumor progression outcomes, especially given the patient population treated.
This study was undertaken to evaluate long-term results of radiofrequency (RF) ablation in patients with colorectal lung metastases and to stratify patients benefitting from lung RF ablation. Lung RF ablation was performed in 78 patients with 198 colorectal lung metastases. Safety, local tumor progression, and survival were evaluated retrospectively. The mean follow-up period after the 140 lung RF ablation sessions was 24.6+/-7.6 months. Pneumothorax and pleural effusion requiring chest tube placement occurred respectively in 18 (12.9%, 18/140) and 2 (1.4%, 2/140) sessions. The respective 1-, 3- and 5-year local tumor progression rates were 10.1% (95% CI, 2.9-17.3%), 20.6% (95% CI, 8.9-22.2%) and 20.6% (95% CI, 8.9-22.2%). The 1-, 3- and 5-year survival rates were 83.9% (95% CI, 75.2-92.7%), 56.1% (95% CI, 41.7-70.5%) and 34.9% (95% CI, 18.0-51.9%), with median survival time of 38.0 months. Univariate analysis revealed maximum tumor diameter of 3 cm or less, single-lung metastasis, lack of extrapulmonary metastasis and normal carcinoembryonic antigen (CEA) level as better prognostic factors. The latter two were significant independent prognostic factors. The 1-, 3- and 5-year survival rates were 97.7% (95% CI, 93.3-100%), 82.5% (95% CI, 68.2-96.8%) and 57.0% (95% CI, 34.7-79.2%) in 54 patients with no extrapulmonary metastases and 96.9% (95% CI, 90.8-100%), 86.1% (95% CI, 71.1-100%) and 62.5% (95% CI, 36.3-88.6%) in 33 patients with negative CEA levels. Lung RF ablation is a safe and useful therapeutic option. These identified prognostic factors will help to stratify patients who benefit from lung RF ablation.
To evaluate the efficacy and tolerability of high-dose stereotactic body radiation therapy (SBRT) for the treatment of patients with one to three lung metastases.
Patients with one to three lung metastases with cumulative maximum tumor diameter smaller than 7 cm were enrolled and treated on a multi-institutional phase I/II clinical trial in which they received SBRT delivered in 3 fractions. In phase I, the total dose was safely escalated from 48 to 60 Gy. The phase II dose was 60 Gy. The primary end point was local control. Lesions with at least 6 months of radiographic follow-up were considered assessable for local control. Secondary end points included toxicity and survival.
Thirty-eight patients with 63 lesions were enrolled and treated at three participating institutions. Seventy-one percent had received at least one prior systemic regimen for metastatic disease and 34% had received at least two prior regimens (range, zero to five). Two patients had local recurrence after prior surgical resection. There was no grade 4 toxicity. The incidence of any grade 3 toxicity was 8% (three of 38). Symptomatic pneumonitis occurred in one patient (2.6%). Fifty lesions were assessable for local control. Median follow-up for assessable lesions was 15.4 months (range, 6 to 48 months). The median gross tumor volume was 4.2 mL (range, 0.2 to 52.3 mL). Actuarial local control at one and two years after SBRT was 100% and 96%, respectively. Local progression occurred in one patient, 13 months after SBRT. Median survival was 19 months.
This multi-institutional phase I/II trial demonstrates that high-dose SBRT is safe and effective for the treatment of patients with one to three lung metastases.
Marked differences in population based survival across Europe were found for colorectal cancers diagnosed in 1985-1989.
To understand the reasons for these differences in survival in a new analysis of colorectal cancers diagnosed between 1988 and 1991.
A total of 2720 patients with adenocarcinoma of the large bowel from 11 European cancer registries (CRs).
We obtained information on stage at diagnosis, diagnostic determinants, and surgical treatment (not routinely collected by CRs) and analysed the data in relation to three year observed survival, calculating relative risks (RRs) of death and adjusting for age, sex, site, stage, and determinants of stage.
Three year observed survival rates ranged from 25% (Cracow) to 59% (Modena), and were low in the Thames area (UK) (38%). Survival rates between registries for "resected" patients varied less than those for all patients. When age, sex, and site were considered, RRs ranged from 0.7 (95% confidence intervals (CI) 0.6-0.9) (Modena) to 2.3 (95% CI 1.9-2.9) (Cracow). After further adjustment by stage, between registry RR variation was between 0.8 (95% CI 0.6-0.9) and 1.8 (95% CI 1.5-2.2). Inter-registry RR differences were slightly reduced when the determinants of stage (number of nodes examined and liver imaging) were included in the model. The reduction was marked for the UK registries.
The wide differences across Europe in colorectal cancer survival depend to a large extent on differences in stage at diagnosis. There are wide variations in diagnostic and surgical practices. There was a twofold range in the risk of death from colorectal cancer even after adjustment for surgery and disease stage.
Preliminary results have shown that percutaneous radiofrequency ablation (RFA) may play a useful role in patients with inoperable lung tumors. This series evaluated the prognostic features for survival in nonsurgical candidates who underwent percutaneous RFA of pulmonary metastases from colorectal carcinoma.
Fifty-five patients not suitable for surgery underwent percutaneous RFA for colorectal pulmonary metastases. All clinical and treatment-related data were collected prospectively. The primary end point of the study was overall survival, defined from the time of RFA intervention. Univariate and multivariate analyses were performed to identify statistically significant prognostic parameters for overall survival.
The overall median survival was 33 months (range, 4-40 months), with actuarial 1-, 2-, and 3-year survival of 85%, 64%, and 46%, respectively. Univariate analysis demonstrated that largest size of lung metastasis (P < .001), location of lung metastases (P = .032), and repeat percutaneous RFA for pulmonary recurrence (P = .024) were statistically significant for overall survival. Multivariate analysis demonstrated that largest size of lung metastasis >3 cm was independently associated with a reduced overall survival (P = .003).
Percutaneous lung RFA may play a useful role in nonsurgical candidates with colorectal pulmonary metastases. However, the survival benefit of this interventional procedure for patients with a pulmonary metastasis >3 cm was limited.
Objectives
To evaluate the prognostic value of carcinoembryonic antigen (CEA) density and other clinicopathological factors for percutaneous ablation of pulmonary metastases from colorectal cancer. MethodsCEA density was calculated as: “absolute serum CEA pre-ablation/volume of all lung metastases [mm3]”. Median CEA density was the cut-off for high and low groups. Cox-regression was used to determine prognostic factors for survival. ResultsA total of 85 patients (102 ablation sessions) were followed for a median of 27 months. High CEA density was significantly associated with worse overall survival compared to low CEA density (adjusted HR: 2.12; 95 % CI: 1.22–3.70, p=0.002; median survival: 25.7 vs. 44.3 months). The interval between primary resection of the colorectal carcinoma and first ablation was also a prognostic factor, a duration >24 months being associated with better survival compared to a shorter interval (0–24 months) (adjusted HR: 0.55; 95 % CI: 0.31–0.98, p=0.04). Moreover, a disease-free interval >24 months was significantly associated with low CEA density compared to a shorter interval (0–24 months) (adjusted OR: 0.29; 95 % CI: 0.11–0.77, p=0.01). Conclusions
Serum CEA density and interval between primary resection of a colorectal carcinoma and pulmonary ablation are independent prognostic factors for overall survival. In two patients with identical CEA serum levels, the patient with the lower/smaller pulmonary tumour load would have a worse prognosis than the one with the higher/larger pulmonary metastases. Key Points• CEA density is an independent prognostic factor for colorectal pulmonary metastases.• A lower CEA density is associated with better overall survival.• CEA may play a functional role in tumour progression.• High CEA density is associated with smaller tumours.• Interval between pulmonary ablation and primary colorectal carcinoma is a prognostic factor.
Objective:
To improve patient selection for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) by evaluating various preoperatively assessable clinicopathological parameters as markers for survival after CRS and HIPEC.
Summary background data:
Peritoneal metastases (PMs) originating from colorectal cancer are treated with CRS and HIPEC. Despite increasing survival, high morbidity and mortality warrant selection of patients with optimal benefit from this treatment. Many studies report a number of variables to be associated with survival after CRS and HIPEC, but no definitive analysis has been made to validate various markers.
Methods:
In concordance with PRISMA guidelines, we performed a literature search encompassing 4110 articles to select 50 articles that reported the influence of 1 or more clinicopathological variables on overall survival after CRS and HIPEC. In absence of RCTs, 25 cohort studies could be used to perform a meta-analysis on 10 prognostic variables.
Results:
We determined that concurrent liver metastasis, lymph node metastasis, Eastern Cooperative Oncology Group score, tumor differentiation, and signet ring cell histology are all negative prognostic variables on overall survival after CRS and HIPEC. Conversely, sex and location of primary could not be validated as prognostic markers. More research is required to make definitive conclusions about neoadjuvant chemotherapy, onset of PMs, and mucinous histology.
Conclusions:
Current clinical practice, which selects patients based on extraperitoneal metastasis, lymph node stage, performance status, and tumor histology, is validated by our pooled analysis. Our data merit further research into neoadjuvant chemotherapy in the setting of CRS and HIPEC for PMs.
Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data were collected by the National Cancer Institute (Surveillance, Epidemiology, and End Results [SEER] Program), the Centers for Disease Control and Prevention (National Program of Cancer Registries), and the North American Association of Central Cancer Registries. Mortality data were collected by the National Center for Health Statistics. In 2016, 1,685,210 new cancer cases and 595,690 cancer deaths are projected to occur in the United States. Overall cancer incidence trends (13 oldest SEER registries) are stable in women, but declining by 3.1% per year in men (from 2009-2012), much of which is because of recent rapid declines in prostate cancer diagnoses. The cancer death rate has dropped by 23% since 1991, translating to more than 1.7 million deaths averted through 2012. Despite this progress, death rates are increasing for cancers of the liver, pancreas, and uterine corpus, and cancer is now the leading cause of death in 21 states, primarily due to exceptionally large reductions in death from heart disease. Among children and adolescents (aged birth-19 years), brain cancer has surpassed leukemia as the leading cause of cancer death because of the dramatic therapeutic advances against leukemia. Accelerating progress against cancer requires both increased national investment in cancer research and the application of existing cancer control knowledge across all segments of the population. CA Cancer J Clin 2016. © 2016 American Cancer Society.
Peritoneal carcinomatosis (PC) results from the secondary spread of many intraabdominal tumour types, such as colorectal malignancy (colorectal cancer, CRC), disseminated peritoneal adenomucinosis (DPAM), appendiceal cancer, ovarian carcinoma, sarcoma or from the occurrence of primary peritoneal disease such as peritoneal mesothelioma. The combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has seen improvements in survival in selected cases of these cancers.
Between 1996 and 2014, a prospective database of 675 patients was created for the peritonectomy unit at our hospital. In total, 827 peritonectomy procedures (including redo CRS) were performed for the major subgroups of PC: DPAM 220; appendiceal cancer (peritoneal mucinous adenocarcinoma (PMCA)) 191; CRC 234; diffuse malignant peritoneal mesothelioma (DMPM) 73 and others 109. There were 152 redo-peritonectomy procedures within the total mentioned earlier (CRC 26; DPAM 58; DMPM 18; appendix 40; other 10).
The 5-year survivals for DPAM and PMCA were 80% and 42% respectively. The 5-year survivals for appendiceal cancer with peritoneal cancer index (PCI) <10, 10-20 and >20 were 60, 57 and 37% respectively (P = 0.09). The 2- and 5-year survivals for CRC were 56 and 24% respectively. The 5-year survivals for PCI 0-5, 6-10, 11-15 and >15 were 59, 15, 7 and 0% respectively (P = 0.000). The 5-year survival for DMPM with PCI < 10, 10-20 and >20 were 100, 55 and 39% respectively (P = 0.01).
CRS in combination with HIPEC provides a chance of long-term survival in selected cases of PC when compared with systemic therapy alone.
© 2015 Royal Australasian College of Surgeons.
We evaluated the long-term outcomes of 157 patients receiving radiofrequency ablation (RFA) to colorectal cancer (CRC) lung metastases.
A total of 434 lesions were ablated in 199 procedures over 14 years. Thirty-two out of the 157 patients underwent multiple procedures. Our primary end-points were overall survival, disease free survival, procedure-related mortality and morbidity and various prognostic entities for survival. The survival in three subgroups were analysed: those that had undergone CRC resection and peritonectomy, CRC resection and liver resection and resection of their primary CRC alone.
105 patients (67%) underwent pre-RFA liver resections, 14 patients (9%) underwent pre-RFA peritonectomies and 58 patients underwent only resection of their primary tumour. There were no procedurally related deaths. The mean duration of follow up was 28 months. A chest drain was required in 18.6% of all procedures. The overall median survival was 33.3 months. Survival at 1, 3 and 5 years was 89, 44 and 19.9% respectively. RFA post liver resection, post peritonectomy and post primary CRC resection alone saw median survivals of 38 months, 26 months and 27 months respectively. Tumour free survival at 12 months, 3 years and 5 years was 60.5%, 14.4% and 7% respectively. Lesion size, lesion number and pre-RFA CEA levels were not prognostic factors for overall survival or disease free survival.
RFA is now an accepted alternative treatment modality for CRC lung metastases in selected groups of patients. RFA has a reasonable morbidity profile and a demonstrated benefit for survival in these patients.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Colorectal cancer is the third most common cancer and the third leading cause of cancer death in men and women in the United States. This article provides an overview of colorectal cancer statistics, including the most current data on incidence, survival, and mortality rates and trends. Incidence data were provided by the National Cancer Institute's Surveillance, Epidemiology, and End Results program and the North American Association of Central Cancer Registries. Mortality data were provided by the National Center for Health Statistics. In 2014, an estimated 71,830 men and 65,000 women will be diagnosed with colorectal cancer and 26,270 men and 24,040 women will die of the disease. Greater than one-third of all deaths (29% in men and 43% in women) will occur in individuals aged 80 years and older. There is substantial variation in tumor location by age. For example, 26% of colorectal cancers in women aged younger than 50 years occur in the proximal colon, compared with 56% of cases in women aged 80 years and older. Incidence and death rates are highest in blacks and lowest in Asians/Pacific Islanders; among males during 2006 through 2010, death rates in blacks (29.4 per 100,000 population) were more than double those in Asians/Pacific Islanders (13.1) and 50% higher than those in non-Hispanic whites (19.2). Overall, incidence rates decreased by approximately 3% per year during the past decade (2001-2010). Notably, the largest drops occurred in adults aged 65 and older. For instance, rates for tumors located in the distal colon decreased by more than 5% per year. In contrast, rates increased during this time period among adults younger than 50 years. Colorectal cancer death rates declined by approximately 2% per year during the 1990s and by approximately 3% per year during the past decade. Progress in reducing colorectal cancer death rates can be accelerated by improving access to and use of screening and standard treatment in all populations.
Background and objectives:
CytoReductive Surgery (CRS) combined with Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) has an established role in the treatment of peritoneally metastasized colorectal cancer. The aim of the study was to describe the recurrence patterns and to evaluate treatment options and related survival.
Methods:
Patients treated with CRS + HIPEC in two tertiary referral centers between April 2005 and March 2013 were analyzed retrospectively. The prognostic value of several parameters was calculated using Cox Regression.
Results:
One hundred thirty two of 287 patients (46%) with peritoneal carcinomatosis treated with complete CRS and HIPEC were diagnosed with recurrent disease, after a median disease-free interval of 11.4 months. Recurrence were locoregional (43%), distant metastases (26%) or both (31%). Thirty-two of the 132 patients with recurrences (24%) were treated surgically with curative intent, which extended the median survival from 12 months to 43 months, compared to palliative treatment (best supportive care or chemotherapy; P < 0.001). Initial nodal status (P = 0.01) and the number of affected regions at initial CRS (P = 0.02) were significantly correlated to survival after disease recurrence.
Conclusion:
Disease recurrence after CRS and HIPEC is common; in selected patients, an aggressive surgical approach may be beneficial and extend survival.
OBJECTIVE:
To investigate the occurrence of synchronous colorectal cancer metastases (SCCM) confined to the lungs, risk factors for these metastases and their impact on survival.
METHODS:
In a nationwide cohort study of 26,200patients data were prospectively entered into the Danish Colorectal Cancer Group's (DCCG's) database between May 2001 and December 2011. The recorded data were merged with data from the Danish Pathology Registry and the National Patient Registry. Multivariable logistic- and extended Cox regression analyses were used to adjust for confounding variables.
RESULTS:
In total, 1970 patients (7.5%) had pulmonary SCCM of whom 736 (37%) had metastases exclusively in the lungs. Advanced age, recent years of diagnosis and a rectal index cancer were significantly associated with pulmonary SCCM. Adjustment for excess use of thoracic CT scans in rectal cancer patients did not alter this association (adjusted OR=1.81 (95% CI: 1.46-2.25, P<0.001)). Patients subjected to pulmonary metastasectomy, resection of primary tumour and chemotherapy had a superior overall survival compared with non-treated patients, especially when these therapeutic modalities were combined.
CONCLUSIONS:
The occurrence of pulmonary SCCM was higher than previously reported and had a severe impact on survival. Our analyses suggest that pulmonary metastasectomy, resection of the primary tumour and chemotherapy may be a sound strategy in patients with confined pulmonary SCCM, but the risk of selection bias and consequent exaggeration of the treatment effect should be kept in mind. This study may serve as a reliable un-biased reference for future evaluation on detection strategies and potential therapeutic interventions.
Surgical resection offers the greatest likelihood of cure for appropriately selected patients with pulmonary colorectal carcinoma metastases. We hereby report our experience over the last 19 years at the Austin Hospital, Thoracic Surgery Unit.
This is a retrospective study of a consecutive series of patients with pulmonary colorectal cancer metastases. From 1994 to 2012, 66 patients underwent 83 pulmonary metastasectomies for colorectal cancer at the Austin Hospital.
Seventy per cent of patients were operated on for single pulmonary metastases. The most common procedure performed was a video-assisted thoracoscopic surgery wedge resection. Median follow-up duration was 25 months. Three-, five-, seven- and ten-year survival was 53.4, 39.6, 34.6 and 23.1%, respectively.
Pulmonary metastasectomy for metastatic colorectal carcinoma continues to offer the greatest survival advantage for appropriately selected patients.
Background:
Long-term survival can be obtained with local treatment of lung metastases from colorectal cancer. However, it is unclear as to what the optimal local therapy is: surgery, radiofrequency ablation (RFA) or stereotactic radiotherapy (SBRT).
Methods:
A systematic review included 27 studies matching with the a priori selection criteria, the most important being ≥50 patients and a follow-up period of ≥24months. No SBRT studies were eligible. The review was therefore conducted on 4 RFA and 23 surgical series.
Results:
Four of the surgical studies were prospective, all others were retrospective. No randomized trial was found. The reporting of data differed between the studies, which led to difficulties in the analyses. Treatment-related mortality rates for RFA and surgery were 0% and 1.4-2.4%, respectively, whereas morbidity rates were reported inconsistently but seemed the lowest for surgery.
Conclusion:
Due to the lack of phase III trials, no firm conclusions can be drawn, although most evidence supports surgery as the most effective treatment option. High-quality trials comparing currently used treatment modalities such as SBRT, RFA and surgery are needed to inform treatment decisions.
Objectives: The International Registry of Lung Metastases was established in 1991 to assess the long-term results of pulmonary metastasectomy. Methods: The Registry has accrued 5206 cases of lung metastasectomy, from 18 departments of thoracic surgery in Europe (n = 13), the United States (n = 4) and Canada (n = 1). Of these patients, 4572 (88%) underwent complete surgical resection. The primary tumor was epithelial in 2260 cases, sarcoma in 2173, germ cell in 363, and melanoma in 328. The disease-free interval was 0 to 11 months in 2199 cases, 12 to 35 months in 1857, and more than 36 months in 1620. Single metastases accounted for 2383 cases and multiple lesions for 2726. Mean follow-up was 46 months. Analysis was performed by Kaplan-Meier estimates of survival, relative risks of death, and multivariate Cox model. Results: The actuarial survival after complete metastasectomy was 36% at 5 years, 26% at 10 years, and 22% at 15 years (median 35 months); the corresponding values for incomplete resection were 13% at 5 years and 7% at 10 years (median 15 months). Among complete resections, the 5-year survival was 33% for patients with a disease-free interval of 0 to 11 months and 45% for those with a disease-free interval of more than 36 months; 43% for single lesions and 27% for four or more lesions. Multivariate analysis showed a better prognosis for patients with germ cell tumors, disease-free intervals of 36 months or more, and single metastases. Conclusions: These results confirm that lung metastasectomy is a safe and potentially curative procedure. Resectability, disease-free interval, and number of metastases enabled us to design a simple system of classification valid for different tumor types. (J Thorac Cardiovasc Surg 1997;113:37-49)
Purpose:
To analyze the factors associated with favorable survival in patients with inoperable colorectal lung metastases treated with percutaneous image-guided radiofrequency ablation.
Methods:
Between 2002 and 2011, a total of 398 metastases were ablated in 122 patients (87 male, median age 68 years, range 29-90 years) at 256 procedures. Percutaneous CT-guided cool-tip radiofrequency ablation was performed under sedation/general anesthesia. Maximum tumor size, number of tumors ablated, number of procedures, concurrent/prior liver ablation, previous liver or lung resection, systemic chemotherapy, disease-free interval from primary resection to lung metastasis, and survival from first ablation were recorded prospectively. Kaplan-Meier analysis was performed, and factors were compared by log rank test.
Results:
The initial number of metastases ablated was 2.3 (range 1-8); the total number was 3.3 (range 1-15). The maximum tumor diameter was 1.7 (range 0.5-4) cm, and the number of procedures was 2 (range 1-10). The major complication rate was 3.9 %. Overall median and 3-year survival rate were 41 months and 57 %. Survival was better in patients with smaller tumors-a median of 51 months, with 3-year survival of 64 % for tumors 2 cm or smaller versus 31 months and 44 % for tumors 2.1-4 cm (p = 0.08). The number of metastases ablated and whether the tumors were unilateral or bilateral did not affect survival. The presence of treated liver metastases, systemic chemotherapy, or prior lung resection did not affect survival.
Conclusion:
Three-year survival of 57 % in patients with inoperable colorectal lung metastases is better than would be expected with chemotherapy alone. Patients with inoperable but small-volume colorectal lung metastases should be referred for ablation.
Unlabelled:
We evaluated the local tumor control and the survival benefit achieved with radiofrequency ablation (RFA) for nonoperable lung metastases in 45 patients with colorectal cancer. Median survival from the time of RFA was 46 months. One-, 2- and 3-year local tumor progression (LTP)-free survival rates were 92%, 77%, and 77%, respectively. RFA offers very good local control in patients with pulmonary metastases from colorectal cancer.
Background:
Radiofrequency ablation has emerged as a potential, lung function-preserving treatment of colorectal lung metastases.
Patients and methods:
Forty-five patients with colorectal pulmonary metastases underwent computed tomography-guided RFA from December 2004 to June 2010. A baseline posttreatment scan was obtained 4-6 weeks after RFA and follow-up imaging studies every 3 months thereafter were obtained and compared to evaluate the tumor progression at site of ablation or elsewhere. The primary end points were LTP-free survival and overall survival from RFA procedure. The Kaplan-Meier method was used to analyze the end points. A Cox proportional hazard model with robust inference was used to estimate the associations between baseline factors and survival end points.
Results:
Sixty-nine metastases were ablated in 45 patients. Tumor size ranged from 0.4 to 3.5 cm. The median number of metastases ablated per patient was 1 (range, 1-3). Median follow-up after RFA was 18 months. Median survival from the time of RFA was 46 months (95% confidence interval [CI], 27.8-47.3). One-, 2- and 3-year overall survival rates from the time of RFA were 95% (95% CI, 82%-99%), 72% (95% CI, 52%-85%), and 50% (95% CI, 26%-71%), respectively. Nine of 69 lesions (13%) progressed and 4 were retreated with no progression after second RFA. Median time to progression was not reached. LTP-free survival from RFA was 92% (95% CI, 82%-97%) at 1 year, 77% (95% CI, 58%-88%) at 2 years, and 77% (95% CI, 58%-88%) at 3 years.
Conclusion:
Radiofrequency ablation of lung metastases is an effective minimally invasive, parenchymal-sparing technique that has very good local control rates in patients with pulmonary metastases from colorectal cancer, with LTP-free survival of 77% at 3 years.
Although systemic therapies have shown to result in survival benefit in patients with metastatic colorectal cancer (mCRC), outcomes in patients with peritoneal carcinomatosis (PC) are poor. No data are available on outcomes of current chemotherapy schedules plus targeted agents in mCRC patients with PC.
Previously untreated mCRC patients treated with chemotherapy in the CAIRO study and with chemotherapy and targeted therapy in the CAIRO2 study were included and retrospectively analysed according to presence or absence of PC at randomisation. Patient demographics, primary tumour characteristics, progression-free survival (PFS), overall survival (OS), and occurrence of toxicity were evaluated.
Thirty-four patients with PC were identified in the CAIRO study and 47 patients in the CAIRO2 study. Median OS was decreased for patients with PC compared with patients without PC (CAIRO: 10.4 versus 17.3 months, respectively (p ≤ 0.001); CAIRO2: 15.2 versus 20.7 months, respectively (p < 0.001)). Median number of treatment cycles did not differ between patients with or without PC in both studies. Occurrence of major toxicity was more frequent in patients with PC treated with sequential chemotherapy in the CAIRO study as compared to patients without PC. This was not reflected in reasons to discontinue treatment. In the CAIRO2 study, no differences in major toxicity were observed.
Our data demonstrate decreased efficacy of current standard chemotherapy with and without targeted agents in mCRC patients with PC. This suggests that the poor outcome cannot be explained by undertreatment or increased susceptibility to toxicity, but rather by relative resistance to treatment.
Cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) treatment of colorectal peritoneal carcinomatosis (PC) is gaining acceptance, but controversy remains. The primary aims were to analyse the outcome and prognostic variables of colorectal PC patients treated with CRS and IPC, and to report on the outcome of additional surgical treatments of subsequent recurrences.
Patients referred for treatment of colorectal PC between 1996 and 2010 were included in a cohort. The following data was collected: clinicopathological parameters, survival, recurrences, perioperative chemotherapy and type of IPC (hyperthermic intraperitoneal chemotherapy, HIPEC; or sequential postoperative intraperitoneal chemotherapy, SPIC). Multivariable analyses were conducted on potential prognostic factors for overall survival (OS).
In the 151-patient cohort, the median OS was 34 months (range: 2-77) for CRS and HIPEC with five-year survival predicted at 40% (five-year disease-free survival 32%). For CRS and SPIC, the OS was 25 months (range: 2-188) with five-year survival at 18%. Open-and-close patients survived 6 months (range: 0-14) with no five-year survival (HIPEC vs. SPIC p = 0.047, SPIC vs. open-and-close p < 0.001). Adjuvant systemic chemotherapy was a noteworthy independent prognostic factor in the multivariable analysis. OS for patients undergoing additional surgical treatment of recurrences was 25 months vs. 10 months with best supportive care or palliative chemotherapy (p = 0.01).
Substantial long-term survival is possible in patients with colorectal PC. HIPEC was associated with better OS than SPIC and adjuvant systemic chemotherapy may improve the outcome in patients. Good OS is achievable in selected patients undergoing additional surgical treatment of isolated liver or peritoneal recurrences after prior complete CRS.
Background:
Perioperative intraperitoneal chemotherapy (PIC) is delivered by intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC). The relative survival benefits of each or both regimens are explored in this large series of patients undergoing cytoreduction at a single institution.
Methods:
Patients with a complete (CCR0) or optimal (CCR1) cytoreduction who received intraperitoneal chemotherapy for appendiceal and colorectal peritoneal carcinomatosis were included for analysis. PIC regimens were delivered according to the treatment protocol. Standardized statistical analyses were performed.
Results:
Of 262 patients, 98 patients (37%) had colorectal peritoneal carcinomatosis, 108 patients (41%) had low-grade pseudomyxoma peritonei and 56 patients (21%) had appendiceal peritoneal carcinomatosis. For pseudomyxoma peritonei, recurrence-free survival (RFS) did not vary with PIC regimen, 5-year survival was 86% in the HIPEC and EPIC group and 64% in the HIPEC or EPIC group (P = 0.070). For appendiceal peritoneal carcinomatosis, RFS and overall survival (OS) did not vary with PIC regimen. For colorectal peritoneal carcinomatosis, the median RFS was 33 months in the HIPEC and EPIC group, 19 months in the HIPEC alone group and 20 months in the EPIC alone group (P = 0.046). OS did not vary with PIC regimen.
Conclusion:
From our experience, without compromising the perioperative morbidity and mortality, PIC consisting of HIPEC and EPIC appears to be associated with potential survival benefits of improved OS in pseudomyxoma peritonei and RFS in colorectal peritoneal carcinomatosis.
The treatment of peritoneal carcinomatosis is based on cytoreduction followed by hyperthermic intraperitoneal chemotherapy and combined with adjuvant chemotherapy. In 2003, a randomized trial was finished comparing systemic chemotherapy alone with cytoreduction followed by hyperthermic intraperitoneal chemotherapy and systemic chemotherapy. This trial showed a positive result favoring the studied treatment. This trial has now been updated to a minimal follow-up of 6 years to show long-term results.
For all patients still alive, the follow-up was updated until 2007. In the original study, four patients were excluded-two because of no eligible histology/pathology and two because of major protocol violations. After randomization, four patients in the HIPEC arm and six in the control arm were not treated using the intended therapy, one patient because of withdrawal, one because of a life-threatening other malignant disease and the others because of progressive disease before initiation of the treatment. During the follow-up, one patient was crossed over from the control arm and underwent cytoreduction and HIPEC for recurrent disease, after the assigned treatment was completed. The data from these patients were censored at the moment of the cross-over. Progression-free and disease-specific survival were analyzed using the Kaplan Meyer test and compared using the log rank method. The long-term results were studied in more detail to evaluate efficacy and toxicity.
At the time of this update, the median follow-up was almost 8 years (range 72-115 months). In the standard arm, 4 patients were still alive, 2 with and 2 without disease; in the "HIPEC' arm, 5 patients were still alive, 2 with and 3 without disease. The median progression-free survival was 7.7 months in the control arm and 12.6 months in the HIPEC arm (P = 0.020). The median disease-specific survival was 12.6 months in the control arm and 22.2 months in the HIPEC arm (P = 0.028). The 5-year survival was 45% for those patients in whom a R1 resection was achieved.
With 90% of all events having taken place up to this time, this randomized trial shows that cytoreduction followed by HIPEC does significantly add survival time to patients affected by peritoneal carcinomatosis of colorectal origin. For a selected group, there is a possibility of long-term survival.
To evaluate our experience of radiofrequency ablation (RFA) of pulmonary metastases in patients with resected colorectal liver metastases who had concomitant or recurrent pulmonary metastases.
Clinical and treatment variables of patients undergoing RFA were collected, and their association with survival was examined. Survival analysis was performed by the Kaplan-Meier method.
RFA was performed as concomitant sequential treatment of extrahepatic pulmonary metastases after hepatectomy in 19 patients (30%) and as salvage treatment for pulmonary recurrences after hepatectomy in 45 patients (70%). Patients undergoing sequential treatment had a median survival of 31 (95% confidence interval [CI] 21.8-40.6) months compared to 59 (95% CI 35.0-82.0) months in the salvage treatment group (P = 0.142). The disease-free survival (DFS) was 9 (95% CI 1.0-18.8) months in the sequential treatment group and 16 (95% CI 8.1-23.1) months in the salvage treatment group (P = 0.023). Liver metastases occurring within 12 months of the primary tumor negatively influenced overall survival (OS) and DFS in the sequential treatment group (P = 0.003 and P = 0.091). Poorly differentiated tumor (P = 0.001) was associated with a poorer OS, and prehepatectomy carcinoembryonic antigen > 200 ng/ml (P = 0.017) and bilateral pulmonary metastases (P = 0.030) were associated with a shorter DFS in the salvage treatment group.
The DFS and OS of patients undergoing sequential RFA of extrahepatic pulmonary metastases after hepatectomy appeared shorter when compared to patients who underwent RFA as salvage treatment for pulmonary recurrences after hepatectomy. It nonetheless remains better than the historical results of chemotherapy alone and thus supports the use of RFA as an ablative technology to achieve tumor control.
The aims of the South Australian Clinical Registry for Metastatic Colorectal Cancer are to record case outcomes according to site of recurrence and mode of clinical practice and to utilize the accumulated information for quality assurance activities.
All patients who had a diagnosis of synchronous or metachronous metastatic colorectal cancer (CRC) after 1 February 2006 were eligible to be included in the registry. Data on patient details, disease characteristics, investigations, histopathology and treatment were collected. Disease-specific survival data were assessed using Kaplan-Meier product moment estimates and the log-rank test of equality was used for comparisons.
1544 patients have been entered as of 22 March 2010. In addition, 54.7% of primary CRCs were in the rectosigmoid area, 92.9% of them adenocarcinomas. Also, 52.6% of patients received chemotherapy and 15% had radiotherapy. Two hundred five patients underwent liver resection, nine had radiofrequency ablation and seven had selective internal radiotherapy. The overall 3-year survival from time of diagnosis of metastatic CRC was 29.5%. There was no significant survival difference between patients with synchronous and metachronous metastatic CRC. Patients with lung- or liver-only metastases have significantly improved survival if they underwent surgical resection.
The treatment of patients with metastatic CRC continues to progress with modern medical and surgical developments. Important insights into the current patterns of care and clinical outcomes for metastatic CRC are provided by these data. In addition, this registry provides a feasible and useful database for the evaluation of current treatments established as best evidence in this population.
In March 2010, a randomized trial called Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) was launched and is open to recruitment. The evidence for pulmonary metastasectomy reviewed in this supplement includes no randomized trials. Claims for a survival benefit for patients undergoing this surgery rely on case series. Furthermore, there is little documentation of any symptoms attributable to pulmonary metastases that are alleviated or obviated by metastasectomy. The PulMiCC study aims are to examine whether or not surgical resection of pulmonary metastases from colorectal cancer lengthens survival and to record systematically the harms and benefits of such surgery and quality of life.
Radiofrequency ablation (RFA) is an alternative to local treatment for pulmonary metastases in patients who are nonsurgical candidates. Based on previously documented efficacy of this treatment, the authors retrospectively studied the prognostic factors for long-term survival.
One hundred patients with unresectable colorectal pulmonary metastases underwent percutaneous RFA. Clinical and treatment variables were collected and evaluated using univariate and multivariate analyses with overall survival as the primary endpoint.
At a median follow-up period of 23 (range, 1 to 96) months from the time of RFA treatment, 49 patients have died. The median overall survival after RFA treatment was 36 months and 5-year overall survival rates of 30%. Univariate analyses demonstrated that histopathological grade (p < .001), time to RFA treatment (p = .017), response to treatment (p < .001), repeat RFA treatments (p = .001), presence of extrapulmonary metastases (p < .001), presence of mediastinal lymphadenopathy (p = .007), and adjunct systemic chemotherapy (p < .001) were associated with overall survival. Multivariate analyses demonstrated that response to RFA treatment (p < .001), repeat RFA treatment (p = .002), presence of extrapulmonary metastases (p = .008), and use of adjunct systemic chemotherapy (p = .05) were independent predictors for survival.
Radiofrequency ablation for colorectal pulmonary metastases represents a step forward towards a nonsurgical option of combining systemic and local treatment for metastatic disease and is a safe treatment with a low risk profile.
Surgery is a safe and effective treatment for patients with lung metastases from colorectal carcinoma. Combining chemotherapy and surgery seems to prolong survival time after metastasectomy. Our purpose was to review the effectiveness of surgery with time and evolving managements.
The records of 127 patients were retrospectively analyzed. The characteristics of primary cancer, lung metastases, resections, and associated therapy were studied according to their incidence on survival.
There were 74 male and 53 female patients (mean age, 65 years); 223 operations were performed and 314 metastases were resected. Completeness of surgery (n = 117) was the main factor for prolonged survival (5- and 10-year survival, 41% and 27%, versus 0%). There was no factor of significantly better prognosis, but a tendency to higher survival rates was observed in cases of single metastasis, in patients undergoing several lung operations, and in patients in whom liver metastases were previously removed. Three of 7 patients with mediastinal lymph node involvement survived more than 5 years; 58 patients were operated on before January 2000, and 59 between January 2000 and December 2007. Five-year survival rates were 35.1% versus 63.5%, respectively (p = 0.0096), probably related to better selection with modern workup, more frequent use of chemotherapy, and repeated pulmonary resections.
Different treatment protocols were reported in the literature and in our series with time, resulting in better survival rates and a more aggressive surgical tendency. The beneficial role of such combined therapy justifies further research, including prospective trials.
Because local therapies directed toward a specific tumor mass are known to be effective for treating early-stage cancers, it should be no surprise that there has been considerable historical experience using local therapies for metastatic disease. In more recent years, increasing interest in the use of local therapy for metastases likely has arisen from improvements in systemic therapy. In the absence of effective systemic therapies, such local treatments were often considered futile given both the difficulty in eliminating all sites of identifiable metastatic disease as well as realities regarding the rapid natural history of uncontrolled tumor dissemination. However, with a higher likelihood of patients surviving longer after effective systemic therapy, even if not cured, the goal of the eradication of residual metastases via potent local therapies can be rationalized. However, this rationalization should be evidence-based so as to avoid harming patients for no established benefit. Although surgical metastectomy remains the most common and first-line standard among local therapies, nonsurgical alternatives, including thermal ablation and stereotactic body radiotherapy, have become increasingly popular because they are generally less invasive than surgery and have demonstrated considerable promise in eradicating macroscopic tumor. Rather than eliminating the need for local therapies, improvements in systemic therapies appear to be increasing the prudent utilization of modern local therapies in patients presenting with more advanced cancer.
Aggressive therapeutic regimens have been advocated for the treatment of peritoneal carcinomatosis from colorectal cancer. It is essential to understand the clinical and histological features that govern the natural history of this condition if the efficacies of novel therapeutic approaches are to be assessed adequately.
A database of 3019 colorectal cancers was used to identify patients with synchronous peritoneal carcinomatosis, patients who developed metachronous peritoneal carcinomatosis, and those without carcinomatosis. Clinical, histological and survival data for the groups were collated and subjected to statistical analysis.
Some 349 patients (13 per cent) with peritoneal carcinomatosis were identified; 214 had synchronous disease and 135 had metachronous carcinomatosis. Some 125 patients (58 per cent) in the synchronous group were free of systemic metastases; 80 of these patients had localized disease. Liver metastases, tumour (T) stage, nodal stage, and venous and perineural invasion were independent predictors of metachronous carcinomatosis. The median survival of patients with synchronous disease was 7 months; survival was adversely affected by the extent of peritoneal carcinomatosis and the T stage of the primary cancer.
Peritoneal carcinomatosis is a common mode of disease progression in patients with colorectal cancer. For the majority of patients the prognosis is poor, but a small number with localized disease may be suitable for further aggressive therapy.
This study aimed to assess the safety and efficacy of imaging-guided percutaneous radiofrequency ablation (RFA) for local control of lung metastases from colorectal cancer (CRC).
Twenty patients with lung metastases from CRC were treated with a RITA Starburst XL electrode and RITA 1500 generator using temperature control and impedance monitoring. Patients received intravenous sedation and analgesia, or local anaesthetic, and stayed in hospital for at least 24 h after treatment. RFA was assessed with computed tomography (CT) at 1 week and 1 month, and then every 3 months.
Forty-four CRC lung metastases in 19 patients were treated successfully at 25 treatment sessions. Five of 19 patients were retreated for new lesions. There were 13 pneumothoraces following the 25 treatments, and six patients required drainage. The median length of follow-up was 730 (range 148-924) days. Six months after treatment CT demonstrated that three lesions had progressed, 25 metastases were stable or smaller, and 11 were no longer visible. At 12 months five metastases had progressed, 11 were smaller or stable, and nine were not visible.
Percutaneous imaging-guided RFA was associated with modest morbidity. RFA can achieve local control of CRC lung metastases: nine of 25 metastases were not visible on CT at 12 months after treatment.
Combined local and distant dissemination for colorectal cancer occurs especially in younger patients. New strategies combining maximal cytoreductive surgery with intraperitoneal and systemic chemotherapy have been used in an attempt to prolong survival with an acceptable morbidity and mortality.
Twenty-seven patients with histologically proven peritoneal carcinomatosis from colorectal cancer had distant metastases in addition to peritoneal carcinomatosis. The goal for treatment in all patients was complete local and distant cytoreduction. Aggressive intraperitoneal and systemic chemotherapy was used. The endpoint for all the analysis was survival from the time of definitive treatment at our Institution. RESULTs: In addition to peritoneal carcinomatosis, 16 patients had liver metastases, six patients had lung metastases, four had liver and lung metastases and one had supraclavicular lymph-node metastases. Median survival time (MST) for the entire group was 15.2 months. Patients that received a complete cytoreductive surgery had a MST of 20.6 months and patients with incomplete cytoreduction had a MST of 9.0 months (p= 0.0471). Post-operative morbidity and mortality was 14.8 and 0%, respectively.
A group of carefully selected patients with peritoneal carcinomatosis and distant metastases from colorectal cancer may benefit from cytoreductive surgery and intraperitoneal chemotherapy.
After treatment of peritoneal carcinomatosis of colorectal cancer origin by cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC), recurrences develop in approximately 80% of patients. This study evaluates the outcome of such recurrences after initial treatment by cytoreduction and HIPEC.
Between November 1995 and May 2003, 106 patients underwent cytoreduction and HIPEC. The progression-free interval, the location of the recurrence, and its treatment were recorded. Factors potentially related to survival after recurrences were studied.
Sixty-nine patients had a recurrence within the study period. For patients who had undergone a gross incomplete initial cytoreduction, the median duration of survival after recurrence was 3.7 months (standard error of the mean [SE], .3). If a complete cytoreduction had been accomplished initially, the median duration of survival after the recurrence was 11.1 months (SE, .9). A shorter interval between HIPEC and recurrence was associated with shorter survival after treatment of recurrence (hazard ratio, .94; SE, .02). After effective initial treatment, a second surgical debulking for recurrent disease resulted in a median survival duration of 10.3 months (SE, 1.9), and after treatment with chemotherapy it was 8.5 months (SE, 1.6). The survival was 11.2 months (SE, .5) for patients who received radiotherapy for recurrent disease. Patients who did not receive further treatment survived 1.9 months (SE, .3).
Treatment of recurrence after cytoreduction and HIPEC is often feasible and seems worthwhile in selected patients. Selection should be based mainly on the completeness of initial cytoreduction and the interval between HIPEC and recurrence.
Colorectal peritoneal carcinomatosis (PC) is a frequent and very lethal event. However, cure may be possible with maximal cytoreductive surgery associated with early postoperative intraperitoneal chemotherapy (EPIC).
Between 1996 and 2000, we conducted a two-center prospective randomized trial comparing EPIC plus systemic chemotherapy with systemic chemotherapy alone, both after complete cytoreductive surgery of colorectal PC. Only 35 patients could be included among the 90 who were theoretically required, mainly because of patient dissatisfaction with the inclusion criteria. For this reason, the trial was stopped prematurely.
Analysis of these 35 patients showed that complete resection of PC resulted in a 2-year survival rate of 60%-far above the classic 10% survival rate among patients with colorectal PC treated with systemic chemotherapy and symptomatic surgery. In this small series, EPIC did not demonstrate any advantage for survival.
This supports the use of complete cytoreductive surgery in selected patients and calls for a prospective randomized trial comparing adjuvant systemic chemotherapy with intraperitoneal chemohyperthermia after complete resection.
Although quality assessment is gaining increasing attention, there is still no consensus on how to define and grade postoperative complications. This shortcoming hampers comparison of outcome data among different centers and therapies and over time.
A classification of complications published by one of the authors in 1992 was critically re-evaluated and modified to increase its accuracy and its acceptability in the surgical community. Modifications mainly focused on the manner of reporting life-threatening and permanently disabling complications. The new grading system still mostly relies on the therapy used to treat the complication. The classification was tested in a cohort of 6336 patients who underwent elective general surgery at our institution. The reproducibility and personal judgment of the classification were evaluated through an international survey with 2 questionnaires sent to 10 surgical centers worldwide.
The new ranking system significantly correlated with complexity of surgery (P < 0.0001) as well as with the length of the hospital stay (P < 0.0001). A total of 144 surgeons from 10 different centers around the world and at different levels of training returned the survey. Ninety percent of the case presentations were correctly graded. The classification was considered to be simple (92% of the respondents), reproducible (91%), logical (92%), useful (90%), and comprehensive (89%). The answers of both questionnaires were not dependent on the origin of the reply and the level of training of the surgeons.
The new complication classification appears reliable and may represent a compelling tool for quality assessment in surgery in all parts of the world.
To review the literature with regard to the incidence and prognostic significance of peritoneal seeding during surgery for primary colorectal cancer (CRC), the incidence of intraperitoneal recurrence of CRC, and the current treatment strategies of established PC of colorectal origin, with special focus on cytoreductive surgery and intraperitoneal chemotherapy (IPEC).
Although hematogenous dissemination forms the greatest threat to patients with CRC, peritoneal carcinomatosis (PC), presumably arising from intraperitoneal seeding of cancer cells, is a relatively frequent event in patients with recurrent CRC.
The PubMed and Medline literature databases were searched for pertinent publications regarding the incidence and prognostic significance of exfoliated tumor cells in the peritoneal cavity during curative surgery for primary CRC, the incidence of intraperitoneal recurrence of CRC, and the therapeutic results of systemic chemotherapy or cytoreductive surgery followed by IPEC.
The incidence of peritoneal seeding during potentially curative surgery for primary CRC, as reported in 12 patient series, varied widely, from 3% to 28%, which may be explained by differences in methods to detect tumor cells. PC is encountered in approximately 7% of patients at primary surgery, in approximately 4% to 19% of patients during follow-up after curative surgery, in up to 44% of patients with recurrent CRC who require relaparotomy, and in 40% to 80% of patients who succumb to CRC. The reported median survival after systemic 5-fluorouracil-based chemotherapy for PC varies from 5.2 to 12.6 months. Median survival after aggressive cytoreductive surgery followed by (hyperthermic) IPEC in selected patients, as reported in 16 patient series, tends to be better and varies from 12 to 32 months at the cost of morbidity and mortality rates of 14% to 55% and 0% to 19%, respectively. One randomized controlled trial has been published confirming the superiority of aggressive surgical cytoreduction and intraperitoneal chemotherapy over strictly palliative treatment.
Peritoneal seeding of cancer cells possibly leading to PC is a rather common phenomenon in patients with CRC. Cytoreductive surgery and adjuvant (hyperthermic) IPEC have been shown to be efficacious in selected patients and should therefore be considered in patients with resectable PC of colorectal origin.
This study critically evaluated the local and overall treatment failure rates after percutaneous radiofrequency ablation (RFA) of pulmonary metastases from colorectal carcinoma.
Fifty-five nonsurgical candidates underwent RFA of colorectal pulmonary metastases. The primary end points of this study were local progression-free survival (PFS) and overall PFS. Univariate and multivariate analyses were performed to identify significant prognostic parameters for local and overall PFS.
The local recurrence rate was 38%. For local PFS, univariate analysis demonstrated that the largest size of lung metastasis, the location of lung metastases, the post-RFA carcinoembryonic antigen level at 1 month, and the post-RFA carcinoembryonic antigen level at 3 months were significant prognostic indicators. In multivariate analysis, a largest size of lung metastasis of >3 cm and a post-RFA carcinoembryonic antigen level of >5 ng/mL at 1 month were independently associated with a reduced local PFS. The overall recurrence rate was 66%. For overall PFS, univariate analysis demonstrated that sex and the largest size of lung metastasis were significant prognostic indicators. In multivariate analysis, a largest size of lung metastasis of >3 cm was independently associated with a reduced overall PFS.
RFA of colorectal pulmonary metastases may have a useful role in local disease control for nonsurgical candidates, but its efficacy in patients with a lung metastasis of >3 cm is limited.
Results after lung radiofrequency (RF) ablation were retrospectively evaluated to determine whether lung RF ablation is an effective therapeutic option for the treatment of unresectable lung metastases from colorectal cancer.
Seventy-one patients with 155 unresectable colorectal lung metastases underwent computed tomography (CT)-guided percutaneous RF ablation at four institutions. The maximum tumor size was 3 cm or less in 61 patients and 3.1-6.0 cm in 10 patients (range, 0.5-6.0 cm; mean, 2.4 cm +/- 1.3). A single tumor was treated in 35 patients and multiple tumors in 36 patients. Extrapulmonary metastases were found in 30 patients. Follow-up with serial CT and positron emission tomography scans was performed from 4 to 42 months after RF ablation (mean, 19 months). Primary end point in this study was patient survival, and secondary end points were evaluation of safety of lung RF ablation and intrapulmonary recurrence.
Pneumothorax developed in 26 (37%) patients, and a chest tube was placed in 14 (20%) of them. Empyema developed in one (1%) patient. Thirty-three (47%) patients developed intrapulmonary recurrence and 19 (58%, 19/33) of them received repeat lung RF ablation. The estimated 3-year survival rate was 46% for all patients. Extrapulmonary metastasis, tumor size, and the carcinoembryonic antigen level were significant prognostic factors in the univariate analysis. The first two factors were significantly independent prognostic factors in the multivariate analysis. Thirty-six patients with small lung metastases (< or =3 cm) and no extrapulmonary metastases had a 3-year survival rate of 78%.
Lung RF ablation is a safe and effective treatment in selected patients with unresectable lung metastases from colorectal cancer.