[Show abstract][Hide abstract] ABSTRACT: Aim: To evaluate survival outcomes of patients in pStage II-III rectal cancer treated with adjuvant 5-fluorouracil-based radiochemotherapy and toretrospectively analyzethe impact of prognostic variables on local control, metastasis-free survival and cause-specific survival.
A total of 1,338 patients, treated between 1985-2005 for locally advanced rectal cancer, who underwent surgery and postoperative 5-fluorouracil-based chemoradiation, were selected.
The actuarial 5- and 10-year outcomes were: local control 87.0%-84.1%, disease-free survival 61.6%-52.1%, metastasis-free survival 72.0%-67.2%, cause-specific survival 70.4%-57.5%, and overall survival 63.8%-53.4%. Better outcomes were observed in patients with IIA, IIIA stage. Multivariate analyses showed that variables significantly affecting metastasis-free survival were pT4 and pN2, while for cancer-specific survival those variables were age >65 years, pT4, pN1, pN2, distal tumors and number of lymph nodes removed ≤12.
This study confirmed that among stage II-III rectal cancer patients there are subgroups of patients with different clinical outcomes.
Anticancer research 10/2013; 33(10):4557-4566. · 1.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background and aim:
To assess the effectiveness of the potential advantages with 3-dimensional-based treatment planning versus 2-dimensional pelvic bone-based treatment planning in patients with rectal cancer, controlled for clinical stage.
Methods and materials:
Areas at risk from computed tomography in 30 patients were delineated: mesorectum, presacral, internal iliac, obturator and external iliac nodes. Two planning target volumes per patient were created: PTV_T3 (M + PSN + ON + IIN) and PTV_T4 (M + PSN + ON + IIN + EIN). Two- and 3-dimensional treatment plans for each planning target volume were calculated. Three analyses were performed: 1) mean volume receiving doses >95% and >105%; according to the percentage of prescribed dose to cover at least 95% of the planning target volume, the treatment plan was defined as optimal dose >95%, acceptable dose between 95% and 90%, inferior dose <90%; 2) comparison of the percentage of volume covered by the dose for 2- vs 3-dimensional; 3) determination of the doses at which the lack of volume coverage started to decrease significantly.
For PTV_T3, the following was seen: 1) 2D vs 3D comparison showed optimal PTV_T3 coverage in 76.7% and 96.7%, respectively; 2) 2D vs 3D TP coverage difference was significant between 29%-95% of the total dose; 3) the lack of volume coverage started at 30% for 2D and 89% for 3D. For PTV_T4, the following was seen: 1) 2D vs 3D comparison showed an optimal PTV_T4 coverage in 33.3% and 86.7%, respectively; 2) 2D vs 3D TP coverage difference was significant between 7%-97% of the total dose; 3) the lack of volume coverage started at 7% for 2D and 87% for 3D.
The 3D treatment planning was superior to 2D treatment planning in covering areas at risk for pelvic recurrence in patients treated for rectal cancer. The areas with suboptimal coverage may lead to an increased risk of recurrence and should be correlated with the patterns of recurrence.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To evaluate in two different settings - clinical practice and education/training - the reliability, time efficiency and the ideal sequence of an atlas-based auto-segmentation system in pelvic delineation of locally advanced rectal cancer.
Fourteen consecutive patients were selected between October and December 2011. The images of four were used as an atlas and 10 used for validation. Two independent operators participated: a Delineator to contour and a Reviewer to perform an independent check (IC). The CTV, pelvic subsites and organs at risk were contoured in four different sequences. These included A: manual; B: auto-segmentation; C: auto-segmentation + manual revision; and D: manual + auto-segmentation + manual revision. Contouring was performed by the Delineator using the same planning CT. All of them underwent an IC by a Reviewer. The time required for all the contours were recorded and overlapping evaluation was assessed using a Dice coefficient.
In the clinical practice setting there have been 13 minutes time saved between sequences A versus sequences B (from 38 to 25 minutes, p = 0.002), a mean Dice coefficient in favor of sequences A for CTV and all subsites (p = 0.0195). In the educational/training setting there have been 35.2 minutes time saved between sequences C and D 8 (from 73.1 min to 37.9 min, p = 0.002).
The preliminary data suggest that the use of an atlas-based auto-contouring system may help improve efficiencies in contouring in the clinical practice setting and could have a tutorial role in the educational/training setting.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to develop accurate models and nomograms to predict local recurrence, distant metastases, and survival for patients with locally advanced rectal cancer treated with long-course chemoradiotherapy (CRT) followed by surgery and to allow for a selection of patients who may benefit most from postoperative adjuvant chemotherapy and close follow-up.
All data (N = 2,795) from five major European clinical trials for rectal cancer were pooled and used to perform an extensive survival analysis and to develop multivariate nomograms based on Cox regression. Data from one trial was used as an external validation set. The variables used in the analysis were sex, age, clinical tumor stage stage, tumor location, radiotherapy dose, concurrent and adjuvant chemotherapy, surgery procedure, and pTNM stage. Model performance was evaluated by the concordance index (c-index). Risk group stratification was proposed for the nomograms.
The nomograms are able to predict events with a c-index for external validation of local recurrence (LR; 0.68), distant metastases (DM; 0.73), and overall survival (OS; 0.70). Pathologic staging is essential for accurate prediction of long-term outcome. Both preoperative CRT and adjuvant chemotherapy have an added value when predicting LR, DM, and OS rates. The stratification in risk groups allows significant distinction between Kaplan-Meier curves for outcome.
The easy-to-use nomograms can predict LR, DM, and OS over a 5-year period after surgery. They may be used as decision support tools in future trials by using the three defined risk groups to select patients for postoperative chemotherapy and close follow-up (http://www.predictcancer.org).
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to translate the Memorial Sloan Kettering Cancer Centre (MSKCC) Bowel Function Instrument into Italian and to test its psychometric validity and reliability in a sample of Italian rectal cancer patients.
The MSKCC questionnaire was translated into Italian using a standard procedure of double-back translation. Construct validity was tested using a factor analysis and internal reliability was estimated using the Cronbach's alpha coefficient. Concurrent validity was determined by correlations with European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-CR38 quality of life scales. A non-parametric analysis of variance was used to establish the discriminant validity of the questionnaire. Test-retest reliability was assessed using the intra-class correlation coefficient.
124 rectal cancer patients participated in the validation study. The number of missing items was 2.2%. The factorial structure was found to be quite similar to the original one and the internal reliability was 0.7 for urgency, 0.6 for frequency, and 0.7 for dietary subscale. The test-retest reliability was acceptable with one exception: the dietary subscale showed a low reproducibility (ICC = 0.4). All three subscales showed a significant correlation with the QLQ-C30 and QLQ-CR38 domains and were able to discriminate several groups of clinical relevance.
The Italian version of the MSKCC Bowel Function Instrument shows acceptable psychometric properties and can be considered a valuable and specific instrument to assess bowel functions in rectal cancer patients, both for research purposes and in clinical practise.
European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 05/2011; 37(7):589-96. DOI:10.1016/j.ejso.2011.04.002 · 3.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the last two decades we have seen major advances in the strategy of the treatment of rectal cancer. Important studies were published to confirm the role of imaging MRI in the treatment plan and in detecting the prognostic factors, the improved outcome of the new surgical technique based on total mesorectal excision and the combined treatments. Many studies demonstrated that MRI is equivalent to histology in measurement of extramural depth, is also highly accurate in staging advanced rectal cancer, in the assessment of mesorectal fascia infiltration and to distinguish cT3 from cT4, in the measuring the distance from the anorectal ring. With the introduction of total mesorectal excision the local recurrence rate is dramatically reduced, especially in selected centres. Preoperative radiotherapy +/- in combination with chemotherapy still reduces this rates respect to only surgery or postoperative treatment. In this time of changing therapeutic approaches, a common standard for large heterogeneous patient groups will likely be substituted by more individualised therapies. It will depend from new evidence of more tailored diagnosis, surgery, radiotherapy and chemotherapy.
European review for medical and pharmacological sciences 04/2010; 14(4):334-41. · 1.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although surgery remains the most important treatment of rectal cancer, the management of this disease has evolved to become more multidisciplinary to offer the best clinical outcome. The International Conference on Multidisciplinary Rectal Cancer Treatment: Looking for an European Consensus' (EURECA-CC2) had the duty to identify the degree of consensus that could be achieved across a wide range of topics relating to the management of rectal cancer helping shape future programs, investigational protocols and guidelines for staging and treatment throughout Europe.
Consensus was achieved using the Delphi method. Eight chapters were identified: epidemiology, diagnostics, pathology, surgery, radiotherapy and chemotherapy, treatment toxicity and quality of life, follow-up, and research questions. Each chapter was subdivided by topic, and a series of statements were developed. Each committee member commented and voted, sentence by sentence three times. Sentences which did not reach agreement after voting round #2 were openly debated during the Conference in Perugia (Italy) December 2008. The Executive Committee scored percentage consensus based on three categories: "large consensus", "moderate consensus", "minimum consensus".
The total number of the voted sentences was 207. Of the 207, 86% achieved large consensus, 13% achieved moderate consensus, and only 3 (1%) resulted in minimum consensus. No statement was disagreed by more than 50% of members. All chapters were voted on by at least 75% of the members, and the majority was voted on by 85%.
This Consensus Conference represents an expertise opinion process that may help shape future programs, investigational protocols, and guidelines for staging and treatment of rectal cancer throughout Europe. In spite of substantial progress, many research challenges remain.
[Show abstract][Hide abstract] ABSTRACT: Our objective was evaluate the outcome of primary clinical T4M0 extraperitoneal rectal cancer treated by neoadjuvant radiochemotherapy. Prognosis of clinical T4 rectal cancer is poor. Preoperative chemoradiation therapy may be beneficial. The results obtained are unclear due to lack of objective and strictly applied staging methods.
Patients with primary, clinical, T4MO, extraperitoneal rectal cancer, defined by transrectal ultrasonography, computed tomography or magnetic resonance imaging, were considered. Intraoperative radiotherapy and adjuvant chemotherapy were employed in some patients after curative resection (R0). Variables influencing the possibility to perform an R0 resection and a sphincter-saving procedure were investigated as predictors of outcome.
100 patients were included. R0 resection was performed in 78 patients. R0 resection rate was greater in females (93% vs 67%) and in responders to neoadjuvant chemoradiation (94% vs 60%). The ability to perform a sphincter-saving procedure was 57%, greater in middle rectal location (85% vs 51%) and in responders to the chemoradiation (70% vs 47%). Median follow-up was 31 months (range, 4-136). Local recurrences were found in 7 patients (10%). Five-year local control in R0 patients was 90% and better in the IORT group (100%). Distant relapse occurred in 24 patients (30%). Five-year overall survival was 59%, and was better after an R0 versus an R1 or R2 resection (68% vs 22%). Overall and disease free survival in R0 patients improved after overall downstaging. Adjuvant chemotherapy given in addition to the neoadjuvant therapy did not appear to offer benefit in improving survival.
A multimodal approach enabled us to obtain a 5-year overall survival of about 60%. IORT increased local control. The role of adjuvant chemotherapy needs to be further investigated.
Surgery 06/2009; 145(5):486-94. DOI:10.1016/j.surg.2009.01.007 · 3.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To report the final data of a Phase I and II study (1839IL/0092) on the combination of an anti-epidermal growth factor receptor drug (gefitinib), infusional 5-fluorouracil, and preoperative radiotherapy in locally advanced, resectable rectal cancer.
Patients received 45 Gy in the posterior pelvis plus a boost of 5.4 Gy on the tumor and corresponding mesorectum. Infusional 5-fluorouracil (5-FU) and gefitinib (250 and 500 mg/day) were delivered during all radiotherapy course. An IORT boost of 10 Gy was allowed. The main endpoints of the study were to establish dose-limiting toxicity (DLT) and to evaluate the rate of pathologic response according to the tumor regression grade (TRG) Mandard score.
A total of 41 patients were enrolled. The DLT was not reached in the 6 patients enrolled in the dose-escalation part of the study. Of the 33 patients in the Phase II, TRG 1 was recorded in 10 patients (30.3%) and TRG 2 in 7 patients (21.2 %); overall 17 of 33 patients (51.5%) had a favorable endpoint. Overall, Grade 3+ toxicity was recorded in 16 patients (41%); these included Grade 3+ gastrointestinal toxicity in 8 patients (20.5%), Grade 3+ skin toxicity in 6 (15.3%), and Grade 3+ genitourinary toxicity in 4 (10.2%). A dose reduction of gefitinib was necessary in 24 patients (61.5%).
Gefitinib can be associated with 5-FU-based preoperative chemoradiation at the dose of 500 mg without any life-threatening toxicity and with a high pCR (30.3%). The relevant rate of Grade 3 gastrointestinal toxicity suggests that 250 mg would be more tolerable dose in a neaoadjuvant approach with radiotherapy and infusional 5-FU.
International journal of radiation oncology, biology, physics 05/2008; 72(3):644-9. DOI:10.1016/j.ijrobp.2008.01.046 · 4.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: When the surgeon analyzes the ongoing literature on the evidence of the neoadjuvant approaches to rectal cancer finds a true paradox: from one side they seem to offer a relative less relevant contribute through the time, in fact whereas in the Swedish trial preoperative radiation yielded a significant improvement of local control and survival, after the introduction of TME the contribution of preoperative chemoradiation is relegate to local control with no or poor influence on survival, even if the absolute 5-year survival rate moved from 40% of the '70 to 60-65% of the latest years. From other side the growing evidence of an incidence of pCR approaching to 30%, seems to identify a subset of patients with more favourable prognosis to neoadjuvant treatments. Furthermore, the overall evidence that 30-35% of rectal cancer patients treated with multimodality therapy still die from cancer namely by distant metastases in spite of the 4-8% of absolute benefit of adjuvant 5Fu based adjuvant chemotherapy, seems to vanish the efforts of the further optimization of the local treatments (surgery and radiotherapy) and of the ongoing modality of delivery the chemotherapeutic agents. We would like to address the main evidences from the literature and the main uncertainties that the surgeon could face to propose a combined treatment to his rectal cancer patient.
[Show abstract][Hide abstract] ABSTRACT: The combination of radiotherapy with chemotherapy is now considered the standard treatment for a number of tumors. However frequently, within radiotherapy as well as medical oncology, considerable skepticism has been expressed about the real impact of this therapeutic modality, in spite of the improvement in terms of outcome seen in numerous trials concerning head and neck, lung, esophageal cancer and tumors of the anal canal, the uterine cervix and pancreas. Considering the evident clinical advantages achieved in the last 2-3 decades, a close collaboration between basic, preclinical and clinical research is desirable to further optimize the outcomes based on the present radiobiological knowledge. As for the preclinical evaluation different methods should be concomitantly used to analyze the pharmacokinetics and mechanism of action; the method of tumor growth delay should be used especially in neoadjuvant clinical settings; the method of tumor control should be used when chemoradiation is aimed at the local cure of the patient independently of subsequent surgery.