Purpose
Many apparent differences exist in aetiology, genetics, anatomy and treatment response between colon cancer (CC) and rectal cancer (RC). This study examines the differences in patient ...characteristics, prevalence of complications and their effect on short-term survival, long-term survival and the rate of recurrence between RC and CC.
Methods
For all stage II–III CC and RC patients who underwent resection with curative intent (2006–2008) in five hospitals in the Netherlands, occurrence of complications, crude survival, relative survival and recurrence rates were compared.
Results
A total of 767 CC and 272 RC patients underwent resection. Significant differences were found for age, gender, emergency surgery, T-stage and grade. CC patients experienced fewer complications compared to RC (
p
= 0.019), but CC patients had worse short-term mortality rates (1.5 versus 6.7 % for 30-day mortality,
p
= 0.001 and 5.2 versus 9.5 % for 90-day mortality,
p
= 0.032). The adjusted HR (overall survival) for CC patients with complications was 1.57 (1.23–2.01;
p
< 0.001) as compared to patients without complications; for RC, the HR was 1.79 (1.12–2.87;
p
= 0.015). Relative survival analyses showed high excess mortality in the first months after surgery and a sustained, prolonged negative effect on both CC and RC. Complications were associated with a higher recurrence rate for both CC and RC; adjusted analyses showed a trend towards a significant association.
Conclusion
Large differences exist in patient characteristics and clinical outcomes between CC and RC. CC patients have a significantly higher short-term mortality compared to RC patients due to a more severe effect of complications.
Summary Background Colonic stenting as a bridge to elective surgery is an alternative for emergency surgery in patients with acute malignant colonic obstruction, but its benefits are uncertain. We ...aimed to establish whether colonic stenting has better health outcomes than does emergency surgery. Methods Patients with acute obstructive left-sided colorectal cancer were enrolled from 25 hospitals in the Netherlands and randomly assigned (1:1 ratio) to receive colonic stenting as a bridge to elective surgery or emergency surgery. The randomisation sequence was computer generated with permuted blocks and was stratified by centre; treatment allocation was concealed by use of a web-based application. Investigators and patients were unmasked to treatment assignment. The primary outcome was mean global health status during a 6-month follow-up, which was assessed with the QL2 subscale of the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire (EORTC QLQ-C30). Analysis was by intention to treat. This study is registered, number ISRCTN46462267. Findings Between March 9, 2007, and Aug 27, 2009, 98 patients were assigned to receive colonic stenting (n=47 patients) or emergency surgery (n=51). Two successive interim analyses showed increased 30-day morbidity in the colonic stenting group, with an absolute risk increase of 0·19 (95% CI −0·06 to 0·41) in analysis of the first 60 patients (14 of 28 patients receiving colonic stenting vs 10 of 32 receiving emergency surgery), and an absolute risk increase of 0·19 (−0·01 to 0·37) in analysis of the first 90 patients (23 of 47 patients vs 13 of 43). In accordance with the advice of the data safety monitoring committee, the study was suspended on Sept 18, 2009, and ended on March 12, 2010. At the final analysis of 98 patients, mean global health status during follow-up was 63·0 (SD 23·8) in the colonic stenting group and 61·4 (SD 21·9) in the emergency surgery group; after adjustment for baseline values, mean global health status did not differ between treatment groups (−4·7, 95% CI −14·8 to 5·5, p=0·36). No difference was recorded between treatment groups in 30-day mortality (absolute risk difference −0·01, 95% CI −0·14 to 0·12, p=0·89), overall mortality (−0·02, −0·17 to 0·14, p=0·84), morbidity (−0·08, −0·27 to 0·11, p=0·43), and stoma rates at latest follow-up (0·09, −0·10 to 0·27, p=0·35). However, the emergency surgery group had an increased stoma rate directly after initial intervention (0·23, 0·04 to 0·40, p=0·016) and a reduced frequency of stoma-related problems (between-group difference −12·0, −23·7 to −0·2, p=0·046). The most common serious adverse events were abscess (three in the colonic stenting group vs four in the emergency surgery group), perforations (six vs none), and anastomotic leakage (five vs one), and the most common adverse events were pneumonia (three vs one) and wound infection (one vs three). Interpretation Colonic stenting has no decisive clinical advantages to emergency surgery. It could be used as an alternative treatment in as yet undefined subsets of patients, although with caution because of concerns about tumour spread caused by perforations. Funding None.
Summary Background If treatment of the axilla is indicated in patients with breast cancer who have a positive sentinel node, axillary lymph node dissection is the present standard. Although axillary ...lymph node dissection provides excellent regional control, it is associated with harmful side-effects. We aimed to assess whether axillary radiotherapy provides comparable regional control with fewer side-effects. Methods Patients with T1–2 primary breast cancer and no palpable lymphadenopathy were enrolled in the randomised, multicentre, open-label, phase 3 non-inferiority EORTC 10981-22023 AMAROS trial. Patients were randomly assigned (1:1) by a computer-generated allocation schedule to receive either axillary lymph node dissection or axillary radiotherapy in case of a positive sentinel node, stratified by institution. The primary endpoint was non-inferiority of 5-year axillary recurrence, considered to be not more than 4% for the axillary radiotherapy group compared with an expected 2% in the axillary lymph node dissection group. Analyses were by intention to treat and per protocol. The AMAROS trial is registered with ClinicalTrials.gov , number NCT00014612. Findings Between Feb 19, 2001, and April 29, 2010, 4823 patients were enrolled at 34 centres from nine European countries, of whom 4806 were eligible for randomisation. 2402 patients were randomly assigned to receive axillary lymph node dissection and 2404 to receive axillary radiotherapy. Of the 1425 patients with a positive sentinel node, 744 had been randomly assigned to axillary lymph node dissection and 681 to axillary radiotherapy; these patients constituted the intention-to-treat population. Median follow-up was 6·1 years (IQR 4·1–8·0) for the patients with positive sentinel lymph nodes. In the axillary lymph node dissection group, 220 (33%) of 672 patients who underwent axillary lymph node dissection had additional positive nodes. Axillary recurrence occurred in four of 744 patients in the axillary lymph node dissection group and seven of 681 in the axillary radiotherapy group. 5-year axillary recurrence was 0·43% (95% CI 0·00–0·92) after axillary lymph node dissection versus 1·19% (0·31–2·08) after axillary radiotherapy. The planned non-inferiority test was underpowered because of the low number of events. The one-sided 95% CI for the underpowered non-inferiority test on the hazard ratio was 0·00–5·27, with a non-inferiority margin of 2. Lymphoedema in the ipsilateral arm was noted significantly more often after axillary lymph node dissection than after axillary radiotherapy at 1 year, 3 years, and 5 years. Interpretation Axillary lymph node dissection and axillary radiotherapy after a positive sentinel node provide excellent and comparable axillary control for patients with T1–2 primary breast cancer and no palpable lymphadenopathy. Axillary radiotherapy results in significantly less morbidity. Funding EORTC Charitable Trust.
Several factors are included in decision making for treatment of patients with locally advanced rectal cancer, including a trade-off between risks and gains of both clinical and functional outcomes. ...However, it is largely unknown which outcomes are most important to patients and whether this differs between patients and clinicians.
Both clinicians and patients treated for locally advanced rectal cancer were invited to fill out an online questionnaire, including a choice-based conjoint experiment. Participants were presented 14 comparisons of two hypothetical case presentations, characterized by different treatments and outcomes of care (6 attributes) and were asked to select the case with the best outcome at that moment. Hierarchical Bayes Estimation was used to calculate the relative importance (RI) of each of the six attributes.
In total, 94 patients and 128 clinicians completed the questionnaire. For patients, avoiding surgery with permanent stoma was most important (RI 24.4, 95%CI 21.88–26.87) and a 2-year difference in disease-free survival was least important (RI 5.6, 95%CI 4.9–6.2). Clinicians assigned highest importance to avoiding severe and daily worries about cancer recurrence (RI 30.7, 95%CI 29.1–32.4), while this was ranked 4th by patients (RI 17.9, 95%CI 16.5–19.4, p < 0.001).
When confronted with different outcomes within one case description, patients find the duration of disease free survival the least important. In addition, considerable differences were found between the importance assigned by patients and clinicians to clinical and functional outcomes, most notably in avoiding surgery with permanent stoma and worries about recurrence.
In this pilot study, we investigated the feasibility of response prediction using digital 18 FFDG PET/computed tomography (CT) and multiparametric MRI before, during, and after neoadjuvant ...chemoradiation therapy in locally advanced rectal cancer (LARC) patients and aimed to select the most promising imaging modalities and timepoints for further investigation in a larger trial.
Rectal cancer patients scheduled to undergo neoadjuvant chemoradiation therapy were prospectively included in this trial, and underwent multiparametric MRI and 18 FFDG PET/CT before, 2 weeks into, and 6-8 weeks after chemoradiation therapy. Two groups were created based on pathological tumor regression grade, that is, good responders (TRG1-2) and poor responders (TRG3-5). Using binary logistic regression analysis with a cutoff value of P ≤ 0.2, promising predictive features for response were selected.
Nineteen patients were included. Of these, 5 were good responders, and 14 were poor responders. Patient characteristics of these groups were similar at baseline. Fifty-seven features were extracted, of which 13 were found to be promising predictors of response. Baseline T2: volume, diffusion-weighted imaging (DWI): apparent diffusion coefficient (ADC) mean, DWI: difference entropy, early response (T2: volume change, DWI: ADC mean change) and end-of-treatment presurgical evaluation MRI (T2: gray level nonuniformity, DWI: inverse difference normalized, DWI: gray level nonuniformity normalized), as well as baseline (metabolic tumor volume, total lesion glycolysis) and early response PET/CT (Δ maximum standardized uptake value, Δ peak standardized uptake value corrected for lean body mass), were promising features.
Both multiparametric MRI and 18 FFDG PET/CT contain promising imaging features to predict response to neoadjuvant chemoradiotherapy in LARC patients. A future larger trial should investigate baseline, early response, and end-of-treatment presurgical evaluation MRI and baseline and early response PET/CT.
Abstract Background and purpose Chemoradiotherapy (CRT) followed by surgery is the standard of care for locally advanced rectal cancer (LARC). For grade ⩾3 acute diarrhea there is a relationship ...between dose and irradiated small bowel volume. The aim of this study was to evaluate whether combined placement of a diverting stoma and sigmoid spacer (DSSS) led to reduced irradiated small bowel volume and less grade ⩾3 acute diarrhea in the treatment of LARC. Materials/methods Between 2003 and 2010, 54 of 189 LARC patients treated with CRT in two institutions had a DSSS prior to CRT. Data on patient and treatment characteristics and outcomes were collected retrospectively. Delineation of small bowel was performed with planning CT-scans. CTCAE version 4.0 was used for acute toxicity. Results Patients with a DSSS had significantly less small bowel volume irradiated up to doses of 20 Gy. This difference was not observed for the higher dose levels. CRT induced grade ⩾3 acute diarrhea was not different between the two groups (8.3% vs. 12.8%; p = 0.41). Conclusion DSSS is not clearly beneficial to reduce grade ⩾3 acute diarrhea, and it must be considered whether placement of a DSSS is justified for this purpose.
Current imaging modalities frequently misjudge disease stage in colorectal, gastric and pancreatic cancer. As treatment decisions are dependent on disease stage, incorrect staging has serious ...consequences. Previous preclinical research and case reports indicate that prostate-specific membrane antigen (PSMA)-targeted PET/CT imaging might provide a solution to some of these challenges. This prospective clinical study aims to assess the feasibility of
FDCFPyL PET/CT imaging to target and visualize primary colon, gastric and pancreatic cancer. In this prospective clinical trial, patients with colon, gastric and pancreatic cancer were included and underwent both
FDCFPyL and
FFDG PET/CT scans prior to surgical resection or (for gastric cancer) neoadjuvant therapy. Semiquantitative analysis of immunohistochemical PSMA staining was performed on the surgical resection specimens, and the results were correlated to imaging parameters. The results of this study demonstrate detection of the primary tumor by
FDCFPyL PET/CT in 7 out of 10 patients with colon, gastric and pancreatic cancer, with a mean tumor-to-blood pool ratio (TBR) of 3.3 and mean SUV
of 3.6. However, due to the high surrounding uptake, visual distinction of these tumors was difficult, and the SUV
and TBR on
FFDG PET/CT were significantly higher than on
FDCFPyL PET/CT. In addition, no correlation between PSMA expression in the resection specimen and SUV
on
FDCFPyL PET/CT was found. In conclusion, the detection of several gastrointestinal cancers using
FDCFPyL PET/CT is feasible. However, low tumor expression and high uptake physiologically in organs/background hamper the clear distinction of the tumor. As a result,
FFDG PET/CT was superior in detecting colon, gastric and pancreatic cancers.
Long-term health-related quality of life is compared between patients with rectal cancer preoperatively treated with long-course chemo radiotherapy (CRT) or with short-course radiotherapy. Apart from ...less satisfaction with urinary function reported by patients who had CRT, no clinically relevant differences in health-related quality of life and patient-reported symptoms between patients who had CRT and short-course radiotherapy were found at 5 years after rectal cancer treatment.
Both preoperative short-course radiotherapy (SC-PRT) and preoperative long-course chemo radiotherapy (CRT) have shown to reduce local recurrence rates after total mesorectal excision (TME), but neither resulted in improved survival. This study compared the long-term health-related quality of life (HRQL) and symptoms between CRT and SC-PRT.
Patients who were preoperatively treated with a total dose of 50.0 to 50.4 Gy for locally advanced rectal cancers were identified from 2 hospital registries. Starting from 2011, all patients who were disease-free in the study population (n = 105) were sent a HRQL-questionnaire composed of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and questions on bowel and urinary function. Patients who underwent SC-PRT in the TME trial were used as a reference group.
HRQL results from 85 patients receiving CRT (81.0%), with a median follow-up time of 58 months, were compared with the results of patients who underwent SC-PRT (n = 306). Apart from more nausea and vomiting reported by patients receiving CRT (mean score for CRT 5.9 vs. 1.3 for SC-PRT; P < .01; not clinically relevant) and less satisfaction with urinary function indicated by patients who received CRT (mean score for CRT 71.2 vs. 81.2 for SC-PRT; P < .01), no significant differences were found in HRQL and symptoms between patients who received CRT and SC-PRT.
This analysis of HRQL in patients who received CRT shows no clinically relevant differences in long-term HRQL and symptoms between patients who received CRT and SC-PRT, apart from less satisfaction with urinary function reported by patients who received CRT. These results indicate that both approaches have a comparable impact on long-term HRQL.
PURPOSE:
METHODS:
RESULTS:All patients were treated preoperatively with a median dose of 50 Gy radiotherapy. Surgery was performed six to ten weeks after radiotherapy. Twenty-seven patients were ...treated with intraoperative radiotherapy because margins were incomplete or ≤2 mm. Postoperative mortality was 2 percent. The median follow-up of all patients was 25.1 months. The overall five-year local control was 65 percent and the overall five-year survival was 50 percent. Positive lymph nodes and incomplete resections negatively influenced local control and overall survival. Intraoperative radiotherapy improved five-year local control (58 vs. 0 percent, P = 0.016) and overall survival (38 vs. 0 percent, P = 0.026) for patients with R1/2 resections.
CONCLUSIONS:
Background
Isolated hepatic perfusion with high-dose chemotherapy is a treatment option for patients with irresectable metastases confined to the liver. Prolonged local control and impact on survival ...have been claimed. Major drawbacks are magnitude and costs of the procedure. We developed an isolated hypoxic hepatic perfusion (IHHP) with retrograde outflow without the need for a heart-lung machine.
Patients and Methods
Twenty-four consecutive patients with irresectable metastases of various origins were treated. IHHP inflow was via the hepatic artery, outflow via the portal vein with occlusion of the retrohepatic caval vein. Radiolabeled albumine was used for leakage monitoring. Melphalan was used at 1–2 mg/kg. A 25-minute perfusion period was followed by a complete washout. Local and systemic melphalan concentrations were determined.
Results
Compared with oxygenated classical IHP, the IHPP procedure reduced operation time from >8 h to 4 hours, blood loss from >4000 to 900 cc and saved material and personnel costs. Leakage was 0% with negligible systemic toxicity and 0% perioperative mortality. Tumor response: complete response (CR) in 4%, partial response (PR) in 58%, and stable disease (SD) in 13%. Median time to progression was 9 months (2–24 months); pharmacokinetics demonstrated intrahepatic melphalan concentrations more than 9 fold higher than postperfusion systemic concentrations.
Conclusions
IHPP is a relatively simple procedure with reduced costs, reduced blood loss, no mortality, limited toxicity, and response rates comparable to classic IHP. The median duration of 9 months of tumor control should be improved. Hereto, vasoactive drugs, will be explored in further studies.
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