Laparoscopic liver resection compared to open approach in patients with colorectal liver metastases improves further resectability: Oncological outcomes of a case-control matched-pairs analysis

Aims

Liver resection is considered the standard treatment of colorectal metastases (CRLM). However, to date, no long term oncological results and data regarding repeat hepatectomy after laparoscopic approach are known. The aim of this study is to analyze single center long-term surgical and oncological outcomes after liver resection for CRLM.

Methods

A total of 57 open resections (OR) were matched with 57 laparoscopic resections (LR) for CRLM. Matching was based mainly on number of metastases, tumor size, segmental position of lesions, type of hepatectomy and type of resection.

Results

Morbidity rate was significantly less in the LR group (p = 0.002); the length of hospital stay was 6.5 ± 5 days for the LR group and 9.2 ± 4 days for the OR group (p = 0.005). After a median follow up of 53.7 months for the OR group and 40.9 months for the LR group, the 5-y overall survival rate was 65% and 60% respectively (p = 0.36) and the 5-y disease free survival rate was 38% and 29% respectively (p = 0.24). More patients in the LR group received a third hepatectomy for CRLM relapse than in the OR group (80% vs. 14.3% respectively; p = 0.015).

Conclusions

Laparoscopic resection for CRLM offers advantages in terms of reduced blood loss, morbidity rate and hospital stay. It provides comparable long-term oncological outcomes but can improve further resectability in patients with recurrent disease.     

Outcome of R1 resection in patients undergoing pancreatico-duodenectomy for pancreatic cancer

Background

Pancreatico-duodenectomy (PD) is the only potentially curative treatment for pancreatic cancer, but most surgeons are reluctant to perform a palliative resection. The aim was to define the outcome for microscopically incomplete PD (R1).

Methods

Ninety-nine consecutive patients underwent laparotomy to perform PD. Sixty-seven patients were resected and 32 underwent palliative bypass (PSB) because of locally advanced disease.

Results

Of the 67 PD, 27 were classified as R0 and 40 as R1. Median survival for R0, R1 and PSB were 24, 18 and 9 months, respectively. Survival in the PSB group was 34% at 1 year and 0% at 2 years. 1-, 2- and 5-year survival in the R0 and R1 groups was 79% and 70%, 48.3% and 39.1%, 21.5% and 9.9%, respectively. Compared to PSB, both other groups were less likely to die over follow-up (p = 0.002). Survival was not significantly different between the R0 and R1 groups (p = 0.21). Perioperative morbidity and mortality were similar in the PD and PSB groups (29.9% and 3.0% vs 31.3 and 3.1%, respectively, p = 1.00).

Conclusions

Better survival in the resection group and similar perioperative risk would support the decision to perform PD even when there is the possibility of incomplete microscopic clearance.     

Perioperative use of the LiMON method of indocyanine green elimination measurement for the prediction and early detection of post-hepatectomy liver failure

Introduction

A non-invasive liver function monitoring system, the LiMON^®, has been developed that measures indocyanine green (ICG) elimination by pulse spectrophotometry. The aim was to assess the relationship between pre and post-operative ICG plasma disappearance rate (ICG PDR %/min) values and the onset of post-hepatectomy liver dysfunction.

Methods

37 patients scheduled for major liver resections were selected. None had chronic liver disease. IGC PDR was measured preoperatively and on days 1, five and 10 postoperatively. On the same day, serum liver function tests were measured.

Results

The median preoperative and post-operative day 1 ICG PDR for the patients who developed liver dysfunction was significantly lower compared to those who did not (p = 0.044, p = 0.014). Significant correlation was found between ICG PDR measurement taken on postoperative day 1 and bilirubin level on day 1 (p = 0.002), 5 (p =<0.001) and 10 (p = 0.001). The same was true for ICG PDR on post-operative day 1 and albumin level on day 5 and 10 (p = 0.003, p < 0.001).

Discussion

LiMON ICG PDR measured by pulse spectophotometry is a quick, non-invasive and reliable liver function test in patients undergoing liver resection that aids in the prediction and early detection of post-hepatectomy liver dysfunction.     

Liver resection for metastatic gastric cancer

Aims

Liver resection represents a curative treatment approach in patients suffering from liver metastases from gastric cancer. However, its value in the treatment of these patients remains controversial. This study was conducted to evaluate the safety and effectiveness of liver resection in these conditions and to identify criteria for the selection of suitable patients.

Methods

From January 1988 to December 2002, 24 patients underwent liver resection for metastatic gastric cancer. The outcome of these 24 patients was retrospectively reviewed using a prospective database. Patient, tumour and operative parameters were analyzed for their influence on long-term survival.

Results

One patient died and four patients (17%) developed complications during the postoperative course. The overall one-, three- and five-year survival was 38%, 16% and 10%, respectively. After curative resection (n = 17), the one-, three- and five-year survival rate was 53%, 22% and 15%, respectively, and patients with metachronous metastases restricted to the liver (n = 5) had a one-, three- and five-year survival of 80%, 40% and 40%, respectively. In the univariate analysis, extrahepatic manifestation showed in tendency (p = 0.069) and resection margins statistically significant (p = 0.005) influence on survival. The multivariate analysis revealed only resection margins as an independent prognostic factor for survival.

Conclusions

Long-term survival can be achieved by liver resection in well selected patients and may be considered in the multidisciplinary treatment approach of metastatic gastric cancer. Patients with metastatic disease restricted to the liver in whom a curative resection can be achieved seem to be most suitable for liver resection.     

Modern post-operative radiotherapy for stage III non-small cell lung cancer may improve local control and survival: A meta-analysis

Background

We hypothesized that modern postoperative radiotherapy (PORT) could decrease local recurrence (LR) and improve overall survival (OS) in patients with stage IIIA-N2 non-small-cell lung cancer (NSCLC).

Methods

To investigate the effect of modern PORT on LR and OS, we identified published phase III trials for PORT and stratified them according to use or non-use of linear accelerators. Non-individual patient data were used to model the potential benefit of modern PORT in stage IIIA-N2 NSCLC treated with induction chemotherapy and resection.

Results

Of the PORT phase III studies, eleven trials (2387 patients) were included for OS analysis and eight (1677 patients) for LR. PORT decreased LR, whether given with cobalt, cobalt and linear accelerators, or with linear accelerators only. An increase in OS was only seen when PORT was given with linear accelerators, along with the most significant effect on LR (relative risk for LR and OS 0.31 (p = 0.01) and 0.76 (p = 0.02) for PORT vs. controls, respectively).Four trials (357 patients) were suitable to assess LR rates in stage III NSCLC treated with surgery, in most cases after induction chemotherapy. LR as first relapse was 30% (105/357) after 5 years. In the modeling part, PORT with linear accelerators was estimated to reduce LR rates to 10% as first relapse and to increase the absolute 5-year OS by 13%.

Conclusions

This modeling study generates the hypothesis that modern PORT may increase both LR and OS in stage IIIA-N2 NSCLC even in patients being treated with induction chemotherapy and surgery.     

Laparoscopic versus open left lateral hepatic sectionectomy: A comparative study

Background

Laparoscopic liver surgery has been difficult to popularize. High volume liver centres have identified left lateral sectionectomy (LLS) as a procedure with potential for transformation into a primarily laparoscopic procedure where surgeons can safely gain proficiency.

Methods

Forty-four patients underwent either laparoscopic (LLLS) or open (OLLS) left lateral sectionectomy (of segments II/III) for focal lesions at Southampton General Hospital.

Results

OLLS and LLLS groups were matched for age, sex and tumour types resected. Median operative time in the LLLS group was 180 (40–340) min and 155 (110–330) min in the OLLS group (p = 0.885) with median intra-operative blood loss in the LLLS group 80 (25–800) ml versus a larger 470 (100–3000) ml; p = 0.002 for patients receiving OLLS. Post-operative stay was also shorter in the LLLS group (3.5 (1–6) days) compared to the OLLS group (7 (3–12) days; p < 0.001). Resection margin was not different in the two groups (11 (1.5–30) mm (LLLS) versus 12 (4–40) mm (OLLS); p = 1) and neither was the complication rate (13% for LLLS versus 25% for OLLS; p = 0.541). There were no conversions to open in the LLLS group and no deaths in either group at 90 days. Between the first and second 12 LLLS the median operative time fell from 240 (70–340) min to 120 (40–120) min; p = 0.005 as well as median post-operative hospital stay from 4.5 (2–6) days to 2 (1–4) days, p = 0.001.

Conclusion

LLLS is a viable alternative to OLLS with potential improvements in intra-operative blood loss and shorter hospital stay without adversely affecting successful resection or complication rates. Larger prospective studies are required to explore this new avenue in laparoscopic liver surgery.     

Management of advanced parotid cancer. A systematic review

Background

Primary adenocarcinomas of the parotid gland are rare and account for less than 5% of all head and neck malignant neoplasms. There is considerable variation in biological behaviour within this group; low-grade tumours exhibit slow growth rates with minimal or no local invasion. High-grade tumours, however, show a high incidence of local recurrence and distant metastasis.

Aim

The purpose of this paper is to analyse the important prognostic indicators for this cancer.

Methods

A systematic review was performed involving 19 published studies from 1987 to 2005 which included 4631 patients. T stage, grade of tumour, N stage and adjuvant radiotherapy on overall (5 year) survival were analysed as prognostic indicators.

Results

T stage (p = 0.041, hazard ratio 1.8 (confidence interval 1.2–2.9)), N stage (p = 0.05, hazard ratio 1.1 (0.2–1.8)), and high-grade (p = 0.001, hazard ratio 2.1 (1.5–2.7)) were associated with a significantly worse survival. The effect of adjuvant radiotherapy was to improve overall survival: p = 0.002, hazard ratio 2.9 (1.5–4.7). The mean 5 year survival for advanced high-grade parotid cancer was 35%.

Conclusion

High-grade advanced parotid cancers are associated with a poor survival. Adjuvant radiotherapy is indicated in these tumours and this improves survival.     

Predictors and prognostic significance of operative complications in patients with hepatocellular carcinoma who underwent hepatic resection

Aims

The morbidity rate of hepatic resection for hepatocellular carcinoma (HCC) remains high. To clarify predictors and the prognostic significance of operative complications in patients with HCC, we conducted a comparative retrospective analysis of 291 patients with HCC who underwent hepatic resection.

Methods

Operative complications included hyperbilirubinemia, ascites, hemorrhage, respiratory and cardiovascular diseases, bile leakage and abscess formation, renal failure, wound infection, and pleural effusion. Predictors of operative complications and their prognostic value for long-term survival were studied by univariate and multivariate analyses.

Results

Mortality and morbidity rates were 7.2% and 42.6%. The main operative complications were ascites (n = 30), intraabdominal abscess (n = 25), hyperbilirubinemia (n = 19), wound infection (n = 16), pleural effusion (n = 10) and intraabdominal hemorrhage (n = 9). By a multivariate logistic regression model, Child–Pugh class B and increased operative blood loss (≥1200 ml) were independent predictors of postoperative complications. Among 243 patients without operative death, the 5-year overall survival rate was significantly lower in patients with operative complications (34.3%) than in those without these complications (48.7%). By the multivariate Cox proportional hazards model, the presence of operative complications was an independent predictor of poor overall survival as well as presence of portal invasion.

Conclusions

Child–Pugh class B and operative blood loss ≥1200 ml were independent predictors of complications after hepatic resection for HCC. Long-term survival is poorer in patients with postoperative complications. Decreasing operative blood loss may result in fewer postoperative complications and better long-term survival of HCC patients.     

Prognostic factors influencing the survival of patients with colon cancer receiving adjuvant 5-FU treatment

Aim

Adjuvant chemotherapy is recommended for stage III colon cancer. The aim of this study was to identify important prognostic factors among patients with colon cancer receiving adjuvant 5-FU-based treatment.

Methods

Data sets of 855 colon cancer patients treated between 1992 and 1999 within a multicenter adjuvant trial comparing 5-FU modulation with folinic acid or interfereron-alpha were examined. Backward elimination in a proportional hazards model was used to identify prognostically relevant clinical and pathological factors.

Results

Tumor recurrence (p < 0.001), duration of adjuvant treatment (p < 0.001), tumor substage (p = 0.004), age (p = 0.005), grading (p = 0.016), treatment-related toxicity (p = 0.021), and treatment (p = 0.031) were identified in descending order of importance as prognostic factors for overall survival.

Conclusions

Adjuvant 5-FU-based treatment should be performed for at least 6 months with a stepwise adjustment of 5-FU doses until toxicity >WHO II. Substages should be reported separately and used for stratification in future trials due to their broad variation in outcome. In the future, this may result in adjuvant treatment of stage III colon cancer adjusted for the risk of substages.     

Circulating tumour cells during laparoscopic and open surgery for primary colonic cancer in portal and peripheral blood

Background

The objective of this study was to detect and quantify circulating tumour cells (CTC) in peripheral and portal blood of patients who had open or laparoscopic surgery for primary colonic cancer.

Methods

Patients in the laparoscopic-group were operated on in a medial to lateral approach (“vessels first”), in the open-group a lateral to medial approach was applied. The enumeration of CTC was performed with the CellSearch System. Intra-operative samples were taken paired-wise (from peripheral and portal circulation) directly after entering the abdominal cavity (T1), after mobilisation of the tumour baring segment (T2), and after tumour resection (T3). Ploidy of both the CTC and tissue of the primary tumour was determined for chromosome 1, 7, 8 and 17.

Results

Thirty-one patients were included; 18 patients had open surgery, 13 patients were operated on laparoscopically. The percentage of samples with CTC at T1 was 7% in peripheral blood and 54% in portal blood (p = 0.002). At T2, 4% and 31% respectively (p = 0.031). And at T3, 4% and 26% respectively (p = 0.125). The cumulative percentage of samples with CTC was significantly higher during open surgery as compared to the laparoscopic approach. Both the CTC and tissue of the primary tumour were diploid for chromosome 1, 7, 8 and 17.

Conclusion

The detection rate and quantity of CTC is significantly increased intra-operatively and is significantly higher in portal blood compared to peripheral blood. Significantly less CTC were detected during laparoscopic surgery probably as result of the medial to lateral approach.     

Adjuvant chemoradiation versus surgery alone for adenocarcinoma of the ampulla of Vater

Background and purpose

To examine the role of adjuvant chemoradiation (CRT) in patients with resected ampullary adenocarcinoma.

Materials and methods

The records of patients who underwent curative surgery for ampullary adenocarcinoma at a single institution between 1992 and 2007 were reviewed. Final analysis included 111 patients, 45% of which also received adjuvant CRT.

Results

Median overall survival (OS) was 36.2 months for all patients. Adverse prognostic factors for OS included T stage (T3/4 vs. T1/T2, p = 0.046), node status (positive vs. negative, p < 0.001), and histological grade (grade 3 vs. 1/2, p = 0.09). Patients receiving CRT were more likely to have advanced T-stage (p = 0.001), node positivity (p < 0.001), and poor histologic grade (p = 0.015). Patients who received CRT were also significantly younger (p = 0.001). On univariate analysis, adjuvant CRT failed to result in a significant difference in survival when compared to surgery alone (median OS: 33.4 vs. 36.2 months, p = 0.969). Patients with node-positive resections who underwent CRT had a non-significant improvement in survival (median OS: 21.6 vs. 13.0 months, p = 0.092). Thirty-three percent of patients developed distant metastasis. Common sites of distant metastasis included liver (23%) and peritoneum (7%).

Conclusions

Adjuvant chemoradiation following curative resection for ampullary adenocarcinoma did not lead to a statistically significant benefit in overall survival. A significant proportion of patients still developed distant metastatic disease suggesting a need for more effective systemic adjuvant therapy.     

Endometrial cancer and venous thromboembolism in women under age 50 who take tamoxifen for prevention of breast cancer: a systematic review

Background

Breast cancer prevention with tamoxifen in high-risk women is limited due to concerns of endometrial cancer and thromboembolism. We report the risk of endometrial cancer, deep vein thrombosis and pulmonary embolism in women <50 years given tamoxifen for breast cancer prevention.

Methods

We searched the Cochrane Central Register of Controlled Trials and National Library of Medicine for published data from January 1970 to December 2010. We contacted principal investigators of clinical trials, and searched Grey literature and conference proceedings for unpublished data. We reviewed three breast cancer prevention trials comparing tamoxifen (20 mg per day) with placebo for five years in high-risk women <50 years. The absolute risk and relative risk (RR) for each outcome were estimated.

Results

The RR for endometrial cancer in women <50 years given tamoxifen is 1.19 (95% CI, 0.53–2.65; p = 0.6) as compared to the placebo. The RR for deep vein thrombosis with tamoxifen is 2.30 (95% CI, 1.23–4.31; p = 0.009) in the active phase of treatment. The risk decreases to 1.00 (95% CI, 0.38–2.67; p = 0.9) in the follow-up phase. The RR for pulmonary embolism with tamoxifen is 1.16 (95% CI, 0.55–2.43; p = 0.6).

Interpretation

The risk of endometrial cancer, deep vein thrombosis and pulmonary embolism is low in women <50 years who take tamoxifen for breast cancer prevention. The risk decreases from the active to follow-up phase of treatment. Education and counseling are the cornerstones of breast cancer chemoprevention.     

Does anti-EGFR therapy improve outcome in advanced colorectal cancer? A systematic review and meta-analysis

Background

Randomised controlled trials (RCTs) of anti-EGFR monoclonal antibodies (MAb) in patients with advanced colorectal cancer (aCRC) have reported conflicting results.

Methods

A systematic review of RCTs comparing standard treatments ± anti-EGFR MAbs was conducted. Hazard ratios (HR) for progression-free (PFS) and overall survival (OS) were derived for patients with wild-type (WT) and mutant KRAS. Prespecified analyses were conducted for line of treatment, MAb used, chemotherapy regimen, and choice of fluouropyrimidine. Trials using bevacizumab on both arms were included in a sensitivity analysis.

Results

Fourteen eligible RCTs were identified, with results by KRAS status available for ten RCTs. For third line treatment, the effect of anti-EGFR MAbs depended on KRAS status (interaction p < 0.00001), with a PFS benefit for patients with WT KRAS only (HR = 0.43, 95% CI 0.35–0.52, p < 0.00001). For first and second line treatment, the effect also appeared to depend on KRAS status (interaction p = 0.0003), again with the PFS benefit only for patients with WT KRAS (HR = 0.83, 95% CI 0.76–0.90, p < 0.0001). Differences between trial results (heterogeneity p = 0.02, I² = 62%) were best explained by the fluouropyrimidine used, with PFS benefits confined to trials combining MAbs alongside 5FU-based chemotherapy (HR = 0.77, 95% CI 0.70–0.85, p < 0.00001). There was no evidence of a PFS benefit when MAbs were given with bevacizumab.

Conclusions

For aCRC patients with WT KRAS, there are clear benefits of anti-EGFR MAbs in the third line and in the first and second line, when used alongside infusional 5FU-based regimens. However, there is no benefit for patients with KRAS mutations.     

Resection with total caudate lobectomy confers survival benefit in hilar cholangiocarcinoma of Bismuth type III and IV

Purpose

To identify prognostic predictors for overall survival of patients with hilar cholangiocarcinoma of Bismuth type III and IV (HCBT34), and to determine survival benefit and safety of total caudate lobectomy (TCL) in a Chinese centre.

Methods

From January 2001 to December 2010, 171 patients with the diagnosis of HCBT34, who underwent a potentially curative resection, were included in this study. Cox proportional hazards regression models were used to determine the association between possible prognostic variables and survival time. Curative resectability rate, morbidity and mortality were investigated also.

Results

Resection with TCL was significantly associated with more opportunity to achieve curative resection (p < 0.01), did not accompany with more morbidity (p = 0.39) and mortality (p = 0.67). Cox regression analysis demonstrated positive resection margins [Relative Risk (RR) 3.6, 95% CI 3.5–3.7], not well differentiation (RR 2.9, 95% CI 2.7–3.1), higher preoperative serum peak CA19-9 level (RR 1.6, 95% CI 1.5–1.7) and regional lymph nodes involvement (RR 1.5, 95% CI 1.4–1.6) as independent adverse prognostic variables.

Conclusions

Resection with TCL offers a long-term survival opportunity for HCBT34, with high curative resectability rates and an acceptable safety profile.     

Comparison of weekly versus every 3 weeks paclitaxel in the treatment of advanced solid tumors: a meta-analysis

Background

Paclitaxel is commonly given as a 3-h infusion every 3 weeks for a variety of malignancies. Several randomized clinical trials comparing weekly paclitaxel with Q3-week (Q3W) have produced mixed results in terms of efficacy and toxicity creating controversy about the ideal dose and schedule.

Methods

A literature search using PubMed, Cochrane Library, and Proceedings of the American Society of Clinical oncology from 1995 to 2011 was performed. We included all published and registered RTCs for advanced solid tumors which compared weekly paclitaxel with Q3W. Primary dependent variables – grade 3, 4 neutropenia rates and grade 3 sensory neuropathy rates – were analyzed for all cancer types. Secondary dependent variables – hazard ratios for survival and response rates – were analyzed for each cancer type. Moderators of cancer types, ethnicity, and paclitaxel dose ratio were analyzed for primary dependent variables.

Results

Ten trials were included. The summary effects of the meta-analysis revealed less grade 3, 4 neutropenia (odds ratio: 0.49, p = 0.0023) and a trend towards less grade 3 sensory neuropathy (odds ratio: 0.54, p = 0.092) with weekly paclitaxel compared with Q3W. Moderator analysis by meta-regression revealed that paclitaxel dose ratios have a significantly positive correlation with rates of G3/4 neutropenia and sensory neuropathy. In the five NSCLC (non small cell lung cancer) trials, the summary effect revealed a better response rate with weekly paclitaxel (odds ratio: 1.24, p = 0.042).

Conclusion

Weekly paclitaxel has a favorable toxicity profile compared to the current standard of Q3W paclitaxel.     

Central retroperitoneal recurrences from colorectal cancer: Are lymph node and locoregional recurrences the same disease?

Background

Central retroperitoneal recurrences (CRRs) from colorectal carcinoma carry a poor prognosis. A CRR is sometimes defined as a locoregional recurrence (LR) and sometimes as a lymph node recurrence (NR). This study was conducted to determine the nature of CRR and evaluate prognostic factors after complete CRR resection.

Methods

Between January 1988 and December 2008, 31 patients underwent a complete resection of CRR. CRRs were divided into NR (n = 23) and LR (n = 8), whether pathological examination disclosed lymph node involvement or not.

Results

No differences were found between LR and NR regarding TNM stage, primary tumour location, time interval from primary tumour resection to CRR, number of metastatic sites, number of metastatic lesions and therapeutic management. The median preoperative CEA level was higher in the NR group (p = 0.003). After a median follow-up of 47 months NRs were associated with better overall survival (OS) (p = 0.03). Three-year OS and disease-free survival (DFS) in the LR and NR groups were 27% and 0% versus 81% and 26%, respectively. Twenty-seven (87%) patients developed a re-recurrence within a median interval of 15 months. The number of metastatic sites or lesions, the size of the CRR, the type of chemotherapy, radiotherapy, the interval between the primary resection and CRR and the TNM stage had no impact on OS.

Conclusion

LR in patients with CRR had a poorer prognosis than NR. A multimodality approach with complete resection may yield long-term survival for NR.     

Surgical management of liver metastases from uveal melanoma: 16 years' experience at the Institut Curie

Background

Uveal melanoma is characterised by a high prevalence of liver metastases and a poor prognosis.

Aim

To review the evolving surgical management of this challenging condition at a single institution over a 16-year period.

Patients and Methods

Between January 1991 and June 2007, among 3873 patients with uveal melanoma, 798 patients had liver metastases. We undertook a detailed retrospective review of their clinical records and surgical procedures. The data was evaluated with both uni- and multivariate statistical analysis for predictive survival indicators.

Results

255 patients underwent surgical resection. The median interval between ocular tumour diagnosis and liver surgery was 68 months (range 19–81). Liver surgery was either microscopically complete (R0; n = 76), microscopically incomplete (R1; n = 22) or macroscopically incomplete (R2; n = 157). The median overall postoperative survival was 14 months, but increased to 27 months when R0 resection was possible.With multivariate analysis, four variables were found to independently correlate with prolonged survival: an interval from primary tumour diagnosis to liver metastases >24 months, comprehensiveness of surgical resection (R0), number of metastases resected (≤4) and absence of miliary disease.

Conclusions

Surgical resection, when possible, is able to almost double the survival and appears at present the optimal way of improving the prognosis in metastatic uveal melanoma. Advances in medical treatments will be required to further improve survival.     

Profiling clinical cancer research across the Atlantic: a review of research and its characteristics presented at ASCO and ESMO Congresses during the last decade

Introduction

The comparison of clinical cancer research characteristics across the Atlantic and their evolution over time have not been studied to date.

Methods

We collected oral presentations on breast, lung and colorectal cancer at ASCO (n = 506) and ESMO (n = 239) Congresses in years 2000–2010.

Results

EU-originated research constituted 52% of all ASCO presentations while US-research 26.7% of ESMO Congress presentations. Industry sponsorship was reported in 24.8% of ASCO vs. 31.8% of ESMO Congress trials. ASCO-presented trials were larger with longer follow-up periods but were blinded less often. ESMO-presented trials used Event-Free Survival (EFS, 38.1%) and Surrogate (18.4%) primary endpoints and reported positive primary endpoints (65%) more often than ASCO-presented trials. Interim analysis resulted in discontinuation of a trial more often at ASCO Congress (8.3% vs. 3.2%). ASCO Congress-presented research was more often published (69.2% vs. 59.8% at ESMO) at higher impact factor journals. Strong trends over the decade were seen for more frequent industry sponsorship, blinded design, larger sample size, early interim discontinuation, use of EFS endpoints and biomarker evaluation.

Conclusions

Cancer clinical research is a complex scientific activity with common global but also distinct characteristics at the two sides of the Atlantic.     

Dose escalation with proton or photon radiation treatment for pancreatic cancer

Purpose

The purpose was to determine the optimal radiation therapy modality (three-dimensional conformal photon-radiation therapy [3DCRT], intensity-modulated photon-radiation therapy [IMRT], or passive-scattering proton therapy [PT]) for safe dose escalation (72 Gy) in pancreatic tumors in different positions relative to organs at risk (OAR) anatomy.

Methods and materials

A 3-cm pancreatic tumor was virtually translated every 5 mm over 5 cm laterally. We generated two plans for each of the three techniques (3DCRT, IMRT, and PT), one that adhered to target coverage objectives and another to meet OAR sparing constraints with best coverage. We evaluated distances between gross tumor volumes and isodoses and compared dose-volume histograms.

Results

IMRT was more conformal in higher gradient dose regions circumferentially, but tumor positions with anteriorly located small bowel benefited more from PT. 3DCRT plans resulted in inadequate target coverage. The V_15Gy (mean ± SD) were as follows for the IMRT and PT plans, respectively: stomach, 48% ± 4% vs 5% ± 3% (p < 0.0001); and small bowel, 61% ± 8% vs 9% ± 4% (p < 0.0001).

Conclusions

Our study showed that the optimal radiation therapy modality for safe dose escalation depends on pancreatic tumor position in relation to OAR anatomy.     

Sparing the penile bulb in the radical irradiation of clinically localised prostate carcinoma: A comparison between MRI and CT prostatic apex definition in 3DCRT, Linac-IMRT and Helical Tomotherapy

Background and purpose

To assess the impact of using MRI and Helical Tomotherapy (HT) compared to 3DCRT and dynamic IMRT on the dose to the penile bulb (PB).

Materials and methods

Eight patients diagnosed with prostate cancer entered a treatment protocol including CT and MRI simulation. The prostate apex was defined on both MRI and CT. Treatment plans (HT, Linac-IMRT, 3DCRT and conventional technique), were elaborated on both MRI and CT images. A dose of 71.4 Gy (2.55 Gy/fraction) was prescribed; it was requested that PTVs be covered by 95% isodose line. The mean dose and V50 of PB were evaluated.

Results

PTV-MRI plans reduced PB mean dose and V50 compared to PTV-CT plans. This improvement, deriving also from the treatment modality, was 89% for 3DCRT, 99% for Linac-IMRT and 97% for HT (p < 0.01), considering V50. Conventional plans resulted in a significantly higher mean PB dose/V50 compared to 3DCRT-PTV-CT (+27%/+38%), Linac-IMRT-PTV-CT (+42%/+57%) and HT-PTV-CT (+32%/+48%) (p < 0.01). The comparison between conventional and PTV-MRI techniques showed a still larger increase: +73%/+93% 3DCRT; +86%/+99% Linac-IMRT; +56%/+99% HT (p < 0.01). The PB mean dose reduction with Linac-IMRT compared to 3DCRT was 24% (p = 0.034) and 40% (p = 0.027) for PTV-CT and PTV-MRI, respectively. This gain remained significant even when comparing Linac-IMRT to HT: 21% (p = 0.07) PTV-CT and 68% (p = 0.00002) PTV-MRI. HT was superior to 3DCRT with respect to PTV-CT (average gain 4%, p = 0.044), whereas it resulted to be detrimental considering PTV-MRI (26 Gy vs 16.5 Gy), possibly due to the helical delivery of HT; however, in a patient where the distance bulb-PTV <1 cm, HT provided better PB sparing than 3DCRT (29.5 Gy vs 45.2 Gy).

Conclusions

MRI allowed efficient sparing of PB irrespective of the treatment modality. Linac-IMRT was shown to further reduce the dose to the bulb compared to 3DCRT and HT.