Liver Irradiation Research Articles

The influence of plan modulation on the interplay effect in VMAT liver SBRT treatments

Volumetric modulated arc therapy (VMAT) uses multileaf collimator (MLC) leaves, gantry speed, and dose rate to modulate beam fluence, producing the highly conformal doses required for liver radiotherapy. When targets that move with respiration are treated with a dynamic fluence, there exists the possibility for interplay between the target and leaf motions. This study employs a novel motion simulation technique to determine if VMAT liver SBRT plans with an increase in MLC leaf modulation are more susceptible to dosimetric differences in the GTV due to interplay effects. For ten liver SBRT patients, two VMAT plans with different amounts of MLC leaf modulation were created. Motion was simulated using a random starting point in the respiratory cycle for each fraction. To isolate the interplay effect, motion was also simulated using four specific starting points in the respiratory cycle. The dosimetric differences caused by different starting points were examined by subtracting resultant dose distributions from each other. When motion was simulated using random starting points for each fraction, or with specific starting points, there were significantly more dose differences in the GTV (maximum 100cGy) for more highly modulated plans, but the overall plan quality was not adversely affected. Plans with more MLC leaf modulation are more susceptible to interplay effects, but dose differences in the GTV are clinically negligible in magnitude.

Implementing Radiation Dose-Volume Liver Response in Biomechanical Deformable Image Registration

Understanding anatomic and functional changes in the liver resulting from radiation therapy is fundamental to the improvement of normal tissue complication probability models needed to advance personalized medicine.The ability to link pretreatment and posttreatment imaging is often compromised by significant dose-dependent volumetric changes within the liver that are currently not accounted for in deformable image registration (DIR) techniques. This study investigated using delivered dose, in combination with other patient factors, to biomechanically model longitudinal changes in liver anatomy for follow-up care and re-treatment planning. Population models describing the relationship between dose and hepatic volume response were produced using retrospective data from 33 patients treated with focal radiation therapy. A DIR technique was improved by implementing additional boundary conditions associated with the dose-volume response in series with a previously developed biomechanical DIR algorithm. Evaluation of this DIR technique was performed on computed tomography imaging from 7 patients by comparing the model-predicted volumetric change within the liver with the observed change, tracking vessel bifurcations within the liver through the deformation process, and then determining target registration error between the predicted and identified posttreatment bifurcation points. Evaluation of the proposed DIR technique showed that all lobes were volumetrically deformed to within the respective contour variability of each lobe.The average target registration error achieved was 7.3mm (2.8mm left-right and anterior-posterior and 5.1mm superior-inferior), with the superior-inferior component within the average limiting slice thickness (6.0mm).This represented a significant improvement (P<.01, Wilcoxon test) over the application of the previously published biomechanical DIR algorithm (10.9mm). This study demonstrates the feasibility of implementing dose-driven volumetric response in deformable registration, enabling improved accuracy of modeling liver anatomy changes, which could allow for improved dose accumulation, particularly for patients who require additional liver radiation therapy.

Validation of the liver mean dose in terms of the biological effective dose for the prevention of radiation-induced liver damage.

The purpose of this study was to determine the optimal mean liver biologically effective dose (BED) to prevent radiation-induced liver disease (RILD) in stereotactic body radiation therapy (SBRT). The actual mean doses appropriate for liver irradiation in modern radiotherapy techniques have not been adequately investigated, although SBRT is sometimes alternatively performed using fractionated regimens. SBRT treatment plans for liver tumors in 50 patients were analyzed. All distributions of the physical doses were transformed to BED2 using the linear-quadratic model. The relationship between physical doses and the BED2 for the liver were then analyzed, as was the relationship between the mean BED2 for the liver and the planning target volume (PTV). A significantly positive correlation was observed between the mean physical dose for the background liver and the mean BED2 for the whole liver (P<0.0001, r=0.9558). Using the LQ model, a mean BED2 of 73 and 16Gy for the whole liver corresponded to the hepatic tolerable mean physical dose of 21 and 6Gy for Child-Pugh A- and B-classified patients, respectively. Additionally, the PTV values were positively correlated with the BEDs for the whole liver (P<0.0001, r=0.8600), and the background liver (P<0.0001, r=0.7854). A mean BED2 of 73 and 16Gy for the whole liver appeared appropriate to prevent RILD in patients with Child-Pugh classes A and B, respectively. The mean BED2 for the liver correlated well with the PTV.

PO-0684: Opposite pharmacokinetics of sorafenib modulates by liver irradiation - concurrent versus sequential

PO-0684: Opposite pharmacokinetics of sorafenib modulates by liver irradiation - concurrent versus sequential

Phase I trial of radiation therapy and sorafenib in unresectable liver metastases

Background and purposeTo determine maximum tolerated dose (MTD) and toxicities of sorafenib combined with stereotactic radiotherapy (SBRT) or whole liver radiotherapy (WLRT) in patients with liver metastases. Material and methodsEligible patients had unresectable liver metastases. Sorafenib dose was escalated in 2 strata: I – SBRT: effective liver volume irradiated (Veff)<80% (30–60Gy in 6 fractions); II – WLRT: Veff>80% (21.6Gy in 6 fractions). Four weeks of sorafenib, with radiotherapy during weeks 2–3, was delivered at 3 escalating dose levels (200–400mg twice daily). Dose limiting toxicity was defined as any grade 3+ liver toxicity, or grade 4+ treatment-related toxicity. ResultsThirty-three patients were treated: 18 in stratum I (median dose 42Gy), 15 in stratum II. The MTD was not reached. Grade 3+ toxicity was seen in 33% of patients, at a median of 10days. Two deaths from non-classic liver toxicity occurred post WLRT in stratum II. The median overall survival was 22.3 and 5.7months for strata I and II respectively. ConclusionsSorafenib and 21.6Gy in 6 fraction WLRT resulted in unacceptably high rates of liver toxicity. Although sorafenib combined with SBRT was tolerable, the observed efficacy does not merit further clinical evaluation.

Baseline hemoglobin and liver function predict tolerability and overall survival of patients receiving radioembolization for chemotherapy-refractory metastatic colorectal cancer.

Patients with liver metastatic colorectal cancer (mCRC) often benefit from receiving 90Y-microsphere radioembolization (RE) administered via the hepatic arteries. Prior to delivery of liver-directed radiation, standard laboratory tests may assist in improving outcome by identifying correctable pre-radiation abnormalities. A database containing retrospective review of consecutively treated patients of mCRC from July 2002 to December 2011 at 11 US institutions was used. Data collected included background characteristics, prior chemotherapy, surgery/ablation, radiotherapy, vascular procedures, 90Y treatment, subsequent adverse events and survival. Kaplan-Meier estimates compared the survival of patients across lines of chemotherapy. The following values were obtained within 10 days prior to each RE treatment: haemoglobin (HGB), albumin, alkaline phosphatase (Alk phosph), aspartate aminotransferase (AST), alanine transaminase (ALT), total bilirubin and creatinine. Common Terminology Criteria Adverse Events (CTCAEs) 3.0 grade was assigned to each parameter and analysed for impact on survival by line of chemotherapy. Consensus Guidelines were used to categorize the parameter grades as either within or outside guidelines for treatment. A total of 606 patients (370 male; 236 female) were studied with a median follow-up was 8.5 mo. (IQR 4.3-15.6) after RE. Fewer than 11% of patients were treated outside recommended RE guidelines, with albumin being the most common, 10.5% grade 2 (<3-2.0 g/dL) at time of RE. All seven parameters showed statistically significant decreased median survivals with any grade >0 (P<0.001) across all lines of prior chemotherapy. Compared to grade 0, grade 2 albumin decreased overall survival 67%; for grade 2 total bilirubin a 63% drop occurred, and grade 1 HGB resulted in 66% lower median survival. Review of pre-RE laboratory parameters may aid in improving median survivals if correctable grade >0 values are addressed prior to radiation delivery. HGB <10 g/dL is a well-known negative factor in radiation response and is easily corrected. Improving other parameters is more challenging. These efforts are important in optimizing treatment response to liver radiotherapy.

Prognostic factors for transarterial chemoembolization combined with sustained oxaliplatin-based hepatic arterial infusion chemotherapy of colorectal cancer liver metastasis.

ObjectiveTo investigate the prognostic factors in chemorefractory colorectal cancer liver metastasis (CRCLM) patients treated by transarterial chemoembolization (TACE) and sustained hepatic arterial infusion chemotherapy (HAIC).MethodsBetween 2006 and 2015, 162 patients who underwent 763 TACE and HAIC in total were enrolled in this retrospective study, including 110 males and 52 females, with a median age of 60 (range, 26–83) years. Prognostic factors were assessed with Log-rank test, Cox univariate and multivariate analyses.ResultsThe median survival time (MST) and median progression-free survival (PFS) of the 162 patients from first TACE/HAIC were 15.6 months and 5.5 months respectively. Normal serum carbohydrate antigen 19-9 (CA19-9, <37 U/mL) (P<0.001) and carbohydrate antigen 72-4 (CA72-4, <6.7 U/mL) (P=0.026), combination with other local treatment (liver radiotherapy or liver radiofrequency ablation) (P=0.034) and response to TACE/HAIC (P<0.001) were significant factors related to survival after TACE/HAIC in univariate analysis. A multivariate analysis revealed that normal serum CA19-9 (P<0.001), response to TACE/HAIC (P<0.001) and combination with other local treatment (P=0.001) were independent factors among them.ConclusionsOur findings indicate that serum CA19-9 <37 U/mL and response to TACE/HAIC are significant prognostic indicators for this combined treatment, and treated with other local treatment could reach a considerable survival benefit for CRCLM. This could be useful for making decisions regarding the treatment of CRCLM.

Investigation of dosimetric variations of liver radiotherapy using deformable registration of planning CT and cone-beam CT.

Many patients with technically unresectable or medically inoperable hepatocellular carcinoma (HCC) had hepatic anatomy variations as a result of interfraction deformation during fractionated radiotherapy. We conducted this retrospective study to investigate interfractional normal liver dosimetric consequences via reconstructing weekly dose in HCC patients. Twenty‐three patients with HCC received conventional fractionated three‐dimensional conformal radiation therapy (3DCRT) were enrolled in this retrospective investigation. Among them, seven patients had been diagnosed of radiation‐induced liver disease (RILD) and the other 16 patients had good prognosis after treatment course. The cone‐beam CT (CBCT) scans were acquired once weekly for each patient throughout the treatment, deformable image registration (DIR) of planning CT (pCT) and CBCT was performed to acquire modified CBCT (mCBCT), and the structural contours were propagated by the DIR. The same plan was applied to mCBCT to perform dose calculation. Weekly dose distribution was displayed on the pCT dose space and compared using dose difference, target coverage, and dose volume histograms. Statistical analysis was performed to identify the significant dosimetric variations. Among the 23 patients, the three weekly normal liver D50 increased by 0.2 Gy, 4.2 Gy, and 4.7 Gy, respectively, for patients with RILD, and 1.0 Gy, 2.7 Gy, and 3.1 Gy, respectively, for patients without RILD. Mean dose to the normal liver (Dmean) increased by 0.5 Gy, 2.6 Gy, and 4.0 Gy, respectively, for patients with RILD, and 0.4 Gy, 3.1 Gy, and 3.4 Gy, respectively, for patients without RILD. Regarding patients with RILD, the average values of the third weekly D50 and Dmean were both over hepatic radiation tolerance, while the values of patients without RILD were below. The dosimetric consequence showed that the liver dose between patients with and without RILD were different relative to the planned dose, and the RILD patients suffered from liver dose over hepatic radiation tolerance. Evaluation of routinely acquired CBCT images during radiation therapy provides biological information on the organs at risk, and dose estimation based on mCBCT could potentially form the basis for personalized response adaptive therapy.

An MRI-based mid-ventilation approach for radiotherapy of the liver

MRI is increasingly being used in radiotherapy of the liver. The purpose of this study was to develop and validate a strategy to acquire MR images for treatment planning and image guidance in the presence of respiratory motion.By interleaving two navigator triggered MRI sequences, a fast but low-resolution image in mid-ventilation (midV) and a high-resolution image in exhale were acquired efficiently. Deformable registration was applied to map the exhale image to the midV anatomy. Cine-MRI scans were acquired for motion quantification.The method was validated with a motion phantom, 10 volunteers and 1 patient with a liver tumor. The time-weighted mean position of a local structure in a cine-scan was defined as the midV-position ground truth and used to determine the accuracy of the midV-triggering method. Deformable registration accuracy was validated using the SIFT algorithm.Acquisition time of the midV/exhale-scan was 3-5min. The accuracy of the midV-position was ⩽0.5±0.5mm for phantom motion and ⩽0.9±1.2mm for the volunteers. Mean residuals after deformable registration were ⩽0.2±1.8mm. The accuracy and reproducibility of the method are within inter- and intra-fraction liver position variability (Case et al., 2009) and could in the future be incorporated in a conventional liver radiotherapy or MR-linac workflow.

Opposite Impact of Breath Hold Level and Variation on Position Shifts in Liver Radiation Therapy With Deep-Inspiration Breath Hold Technique

Opposite Impact of Breath Hold Level and Variation on Position Shifts in Liver Radiation Therapy With Deep-Inspiration Breath Hold Technique

Radio protective effect of black mulberry extract on radiation-induced damage in bone marrow cells and liver in the rat

Ionizing radiation by producing free radicals induces tissue oxidative stress and has clastogenic and cytotoxic effects. The radio protective effect of black mulberry extract (BME) has been investigated on liver tissue and bone marrow cells in the rat. Intraperitoneal (ip) administration of 200mg/kg BME three days before and three days after 3Gy and 6Gygamma irradiation significantly reduced the frequencies of micro nucleated polychromatic erythrocytes (MnPCEs) and micro nucleated norm chromatic erythrocyte (MnNCEs) and increased PCE/PCE+NCE ratio in rat bone marrow compared to the non-treated irradiated groups. Moreover, this concentration of BME extract decreased the level of malondialdehyde (MDA) and superoxide dismutase (SOD), as well as enhanced the total thiol content and catalase activity in rat's liver compared to the non-treated irradiated groups. It seems that BME extract with antioxidant activity reduced the genotoxicity and cytotoxicity induced by gamma irradiation in bone marrow cells and liver in the rat.

Investigation of optimal beam margins for LINAC-based stereotactic extracranial radiotherapy (SBRT) with VMAT technique: A “pareto fronts” approach

Introduction In stereotactic body radiotherapy (SBRT), the objectives of ablative high-dose to the tumour and minimal dose to the surrounding normal tissues are inherently in conflict. Pareto fronts are a powerful mathematical strategy to formalize the trade-off between a given set of mutually contradicting objectives. Purpose To determine the optimal block margin and prescription isodose for both optimal target coverage and normal tissue sparing in SBRT treatments of liver metastases using VMAT technique. Materials and methods Three spherical-shaped targets (PTVs = 20, 55 and 101cc) were selected. A single fraction dose of 26 Gy was prescribed (PD). VMAT plans were generated with Ergo++ TPS using a 6 MV single arc. Pareto fronts based on (i) different MLC block margin around PTV (ranging from +4 mm to −2 mm) and (ii) different prescription isodose surface (IDS) ranging from 50% to 100% of PD were produced. For each block margin, the greatest IDS fulfilling the two criteria: 95% and 99% of PTV volume reached 100% and 90% of PD, respectively, was considered as providing the optimal clinical plan for PTV coverage. Liver Dmean were used against the PTV coverage (1-V100) to generate the fronts. Conformity (CI = V100/PTV), gradient (GI = V50/V100) and homogeneity (HI = D2%/PD) indexes were calculated to compare different plans Results About 300 plans were calculated to generate the fronts. The fronts for 1mm MLC margin provided the best plans in terms of minimal liver irradiation; optimal clinical plans were obtained for IDS equal to 77–82%. GI shows a U-shaped behaviour with respect to prescribed IDS, CI and HI indexes, with minimum values at 1mm for all metrics. The location of these minimal points was found independent of tumour dimensions. Minimal GI values were found at HI values approximately equal to 1.3. Conclusion Pareto fronts provides a rigorous strategy to choice clinical optimal plans in SBRT treatments. We show that a 1 mm MLC block margin provides the best results with regard healthy liver tissue irradiation and steepness of dose fallout.

Fiducial marker guided stereotactic liver radiotherapy: Is a time delay between marker implantation and planning CT needed?

To minimize the risk of marker migration in fiducial marker guided liver SBRT it is common to add a delay of a week between marker implantation and planning CT. This study found that such a delay is unnecessary and could be avoided to minimize the treatment preparation time.

Radiothérapie des tumeurs hépatiques

Recent technological developments led to develop the concept of focused liver radiation therapy. We must distinguish primary and secondary tumors as the indications are restricted and must be discussed as an alternative to surgical or medical treatments. For hepatocellular carcinoma 5 to 10cm (or more), a conformational radiation with or without intensity modulation is performed. Stereotactic body radiotherapy (SBRT) is being evaluated and is increasingly proposed as an alternative to radiofrequency ablative treatment for primary or secondary tumors (typically less than 5cm). Tumor (and liver) movements induced by respiratory motions must be taken into account. Strict dosimetric criteria must be met with particular attention to the dose–volume histograms to liver and the hollow organs, including cases of SBRT.

Radiotherapy in the multidisciplinary treatment of liver cancer: a survey on behalf of the Italian Association of Radiation Oncology

To report the results of the first Italian survey investigating the role of liver-directed radiotherapy in the multidisciplinary approach of primary and metastatic liver cancer. A 21-item, two-section questionnaire was sent to all Italian radiotherapy centers on June 2014. The two sections aimed at: (1) evaluating the presence of a multidisciplinary liver tumor board and describing the role of radiation oncologists within the latter, (2) analyzing Radiotherapy treatment details and differences between centers. A total of 37 centers completed the survey. A multidisciplinary liver tumor board was available in most centers (73%), with a radiation oncologist routinely attending the latter in the majority of cases (85%). Most of the respondents considered liver-directed Radiotherapy as the third line choice when other therapies were not indicated or technically suitable. 18 centers reported the use of liver-directed radiotherapy. The majority of centers started liver irradiation after 2010. The most adopted motion management strategy was abdominal compression. The most adopted GTV-CTV expansion was 0 and 5mm for metastases and hepatocellular carcinoma, respectively. Stereotactic body radiotherapy was the technique of choice; several treatment schedules were registered, being 45Gy in three fractions the most reported fractionation scheme. Dose was prescribed at the PTV margin in most cases. Liver-directed radiotherapy represents a new field of interest which is currently adopted by 10% of all Italian Centers. The technical equipment seems adequate. The variations observed in the treatment regimens reflect the lack of a well-established standard schedule.

SU‐D‐BRB‐01: A Comparison of Learning Methods for Knowledge Based Dose Prediction for Coplanar and Non‐Coplanar Liver Radiotherapy

Purpose:The predictive power of knowledge based planning (KBP) has considerable potential in the development of automated treatment planning. Here, we examine the predictive capabilities and accuracy of previously reported KBP methods, as well as an artificial neural networks (ANN) method. Furthermore, we compare the predictive accuracy of these methods on coplanar volumetric‐modulated arc therapy (VMAT) and non‐coplanar 4π radiotherapy.Methods:30 liver SBRT patients previously treated using coplanar VMAT were selected for this study. The patients were re‐planned using 4π radiotherapy, which involves 20 optimally selected non‐coplanar IMRT fields. ANNs were used to incorporate enhanced geometric information including liver and PTV size, prescription dose, patient girth, and proximity to beams. The performance of ANN was compared to three methods from statistical voxel dose learning (SVDL), wherein the doses of voxels sharing the same distance to the PTV are approximated by either taking the median of the distribution, non‐parametric fitting, or skew‐normal fitting. These three methods were shown to be capable of predicting DVH, but only median approximation can predict 3D dose. Prediction methods were tested using leave‐one‐out cross‐validation tests and evaluated using residual sum of squares (RSS) for DVH and 3D dose predictions.Results:DVH prediction using non‐parametric fitting had the lowest average RSS with 0.1176(4π) and 0.1633(VMAT), compared to 0.4879(4π) and 1.8744(VMAT) RSS for ANN. 3D dose prediction with median approximation had lower RSS with 12.02(4π) and 29.22(VMAT), compared to 27.95(4π) and 130.9(VMAT) for ANN.Conclusion:Paradoxically, although the ANNs included geometric features in addition to the distances to the PTV, it did not perform better in predicting DVH or 3D dose compared to simpler, faster methods based on the distances alone. The study further confirms that the prediction of 4π non‐coplanar plans were more accurate than VMAT.NIH R43CA183390 and R01CA188300

SU‐G‐JeP4‐06: Evaluation of Interfractional and Intrafractional Tumor Motion in Stereotactic Liver Radiotherapy, Based On Four‐Dimensional Cone‐Beam Computed Tomography Using Fiducial Markers

Purpose:The purpose of this study was to evaluate the interfractional and intrafractional motion of liver tumors in stereotactic body radiation therapy (SBRT), based on four‐dimensional cone‐beam computed tomography using fiducial markers. (4D‐CBCT).Methods:Seven patients with liver tumors were treated by SBRT with abdominal compression (AC) in five fractions with image guidance based on 4D‐CBCT. The 4D‐CBCT studies were performed to determine the individualized internal margin for the planning simulation. The interfractional and intrafractional changes of liver tumor motion for all patients was measured, based on the planning simulation 4D‐CBCT, pre‐SBRT 4D‐CBCT, and post‐SBRT 4D‐CBCT. The interfractional motion change was calculated from the difference in liver tumor amplitude on pre‐SBRT 4D‐CBCT relative to that of the planning simulation 4D‐CBCT for each fraction. The intrafractional motion change was calculated from the difference between the liver tumor amplitudes of the pre‐ and post‐SBRT 4D‐CBCT for each fraction. Significant interfractional and intrafractional changes in liver tumor motion were defined as a change ≥3 mm. Statistical analysis was performed using the Pearson correlation.Results:The values of the mean amplitude of liver tumor, as indicated by planning simulation 4D‐CBCT, were 1.6 ± 0.8 mm, 1.6 ± 0.9 mm, and 4.9 ± 2.2 mm in the left‐right (LR), anterior‐posterior (AP), and superior‐inferior (SI) directions, respectively. Pearson correlation coefficients between the liver tumor amplitudes, based on planning simulation 4D‐CBCT, and pre‐SBRT 4D‐CBCT during fraction treatment in the LR, AP, and SI directions were 0.6, 0.7, and 0.8, respectively. Interfractional and intrafractional motion changes of ≥3 mm occurred in 23% and 3% of treatment fractions, respectively.Conclusion:The interfractional and intrafractional changes of liver tumor motion were small in most patients who received liver SBRT with AC. In addition, planning simulation 4D‐CBCT was useful for representing liver tumor movement in patients undergoing SBRT.This work was supported by JSPS KAKENHI Grant Number 26861004.

Induction of Lipocalin2 in a Rat Model of Lung Irradiation.

Previously, we showed that lipocalin2 (LCN2) serum levels increased after liver irradiation and during acute-phase conditions. Here, we evaluate LCN2 expression and serum levels after single-dose lung irradiation with 25 Gy, percutaneously administered to the lung of randomly-paired male Wistar rats. Due to the concave anatomy of the lung recesses, the irradiation field included the upper part of the liver. No rat died due to irradiation. In control tissue, lung immunohistochemistry showed a high constitutive expression of LCN2+ granulocytes. LCN2 mRNA levels in lung tissue increased up to 24 h (9 ± 2.3-fold) after irradiation. However, serum LCN2 levels remained undetectable after lung irradiation. LCN2 expression in the upper part of the liver increased up to 4.2-fold after lung irradiation, but the lower liver showed an early decrease. Acute-phase cytokines (IL-1β and TNF-α) showed a significant increase on transcript level in both lung and upper liver, whilst the lower liver did not show any considerable increase. In conclusion, constitutive expression of LCN2 in local immune cells demonstrates its local role during stress conditions in the lung. The absence of LCN2 in the serum strengthens our previous findings that the liver is the key player in secreting LCN2 during stress conditions with liver involvement.

Prospective phase II trial of regional hyperthermia and whole liver irradiation for numerous chemorefractory liver metastases from colorectal cancer.

PurposeA prospective phase II trial was conducted to evaluate the effectiveness and toxicity of regional hyperthermia and whole liver irradiation (WLI) for numerous chemorefractory liver metastases from colorectal cancer.Materials and MethodsEnrolled patients had numerous chemorefractory hepatic metastases from colorectal cancer. Five sessions of hyperthermia and seven fractions of 3-gray WLI were planned. Health-related quality of life (HRQoL) was determined using the Korean version of the European Organization for Research and Treatment of Cancer quality of life questionnaire C-30 and the Functional Assessment of Cancer Therapy-Hepatobiliary version 4.0. Objective and pain response was evaluated.ResultsA total of 12 patients consented to the study and the 10 who received WLI and hyperthermia were analyzed. WLI was completed as planned in nine patients and hyperthermia in eight. Pain response was partial in four patients and stable in four. Partial objective response was achieved in three patients (30.0%) and stable disease was seen in four patients at the 1-month follow-up. One patient died 1 month after treatment because of respiratory failure related to pleural metastasis progression. Other grade III or higher toxicities were detected in three patients; however, all severe toxicities were related to disease progression rather than treatment. No significant difference in HRQoL was noted at the time of assessment for patients who were available for questionnaires.ConclusionCombined WLI and hyperthermia were well tolerated without severe treatment-related toxicity with a promising response from numerous chemorefractory hepatic metastases from colorectal cancer.

Multidisciplinary treatment and survival analysis for 497 cases of pancreatic cancer with liver metastases

To explore the multidisciplinary therapeutic mode, clinical effect and prognostic factors of pancreatic cancer with liver metastases (PCLM). We retrospectively selected 497 consecutive patients with PCLM who were pathologically diagnosed and treated at Tianjin Medical University Cancer Hospital, from January, 2000 to December, 2012. Clinical characteristics, treatment modality, survival condition and factors associated with prognosis of these cases were analyzed, and efficacy of multidisciplinary treatment model was evaluated. Of these patients, the male/female ratio was 1.85∶1, with a median age of 59. A total of 358 (72.0%) cases had synchronous liver metastases, and 173 (34.8%) cases complicated with extrahepatic metastases. The 0.5, 1, 3, 5 year survival rates of 497 patients were 44.1%, 19.7%, 3.2% and 2.2%, respectively, with a median survival (MS) of 5.4 months. Patients who were treated with 3 or more approaches (including surgery, chemotherapy, radiation therapy, interventional therapy, and physiotherapy) had a longer median survival time than patients treated with 2 or only 1 approach (MS: 8.6 vs 5.2 vs 4.6 months, P< 0.001). Multivariate analysis for clinical features and treatment modality showed that age, weight loss, ascites, karnofsky performance score (KPS), primary site resection, albumin, carbohydrate antigen (CA) 19-9, resection of liver metastases, radiation therapy and systemic chemotherapy were prognostic variables with statistical significance. PCLM is a refractory malignant tumor. Age >60, weight loss (≥10% within 3 months), ascites, KPS <80, albumin<35 g/L, and CA19-9 ≥500 U/ml were the most relevant predictors of poor survival. Multimodal treatment using curative resection of pancreatic cancer and/or liver metastases, systemic chemotherapy and radiation therapy may improve the prognosis and survival rate sufficiently.