Risk-Adapted Neoadjuvant Chemoradiotherapy in Rectal Cancer: Final Report of the OCUM Study.

PURPOSE: We investigated whether neoadjuvant chemoradiotherapy (nCRT) in patients with rectal cancer can be restricted to those at high risk of locoregional recurrence (LR) without compromising oncological outcomes. PATIENTS AND METHODS: In a prospective multicenter interventional study, patients with rectal cancer (cT2-4, any cN, cM0) were classified according to the minimal distance between the tumor, suspicious lymph nodes or tumor deposits, and mesorectal fascia (mrMRF). Patients with a distance >1 mm underwent up-front total mesorectal excision (TME; low-risk group), whereas those with a distance ≤1 mm and/or cT4 and cT3 tumors in the lower rectal third received nCRT followed by TME surgery (high-risk group). The primary end point was 5-year LR rate. RESULTS: Of the 1,099 patients included, 884 (80.4%) were treated according to the protocol. A total of 530 patients (60%) underwent up-front surgery, and 354 (40%) had nCRT followed by surgery. Kaplan-Meier analyses revealed 5-year LR rates of 4.1% (95% CI, 2.7 to 5.5) for patients treated per protocol, 2.9% (95% CI, 1.3 to 4.5) after up-front surgery, and 5.7% (95% CI, 3.2 to 8.2) after nCRT followed by surgery. The 5-year rate of distant metastases was 15.9% (95% CI, 12.6 to 19.2) and 30.5% (95% CI, 25.4 to 35.6), respectively. In a subgroup analysis of 570 patients with lower and middle rectal third cII and cIII tumors, 257 (45.1%) were at low-risk. The 5-year LR rate in this group was 3.8% (95% CI, 1.4 to 6.2) after up-front surgery. In 271 high-risk patients (involved mrMRF and/or cT4), the 5-year rate of LR was 5.9% (95% CI, 3.0 to 8.8) and of metastases 34.5% (95% CI, 28.6 to 40.4); disease-free survival and overall survival were the worst. CONCLUSION: The findings support the avoidance of nCRT in low-risk patients and suggest that in high-risk patients, neoadjuvant therapy should be intensified to improve prognosis.

Selection of patients with rectal cancer for neoadjuvant therapy using pre-therapeutic MRI - Results from OCUM trial.

PURPOSE: No consensus is available on the appropriate criteria for neoadjuvant chemoradiotherapy selection of patients with rectal cancer. The purpose was to evaluate the accuracy of MRI staging and determine the risk of over- and undertreatment by comparing MRI findings and histopathology. METHOD: In 609 patients of a multicenter study clinical T- and N categories, clinical stage and minimal distance between the tumor and mesorectal fascia (mrMRF) were determined using MRI and compared with the histopathological categories in resected specimen. Accuracy, sensitivity, specificity, positive predictive, and negative predictive value (NPV) were calculated. Overstaging was defined as the MRI category being higher than the histopathological category. mrMRF and circumferential resection margin (CRM) were judged as tumor free at a minimal distance > 1 mm. The chi-squared test or Fisher's exact test were used. P < 0.05 was considered significant. RESULTS: The T category was correct in 63.5% (386/608) of patients; cT was overstaged in 22.9% (139/608) and understaged in 13.5% (82/608). MRI accuracy for lymph node involvement was 56.5% (344/609); 22.2% (28/126) of patients with clinical stage II and 28.1% (89/317) with clinical stage III disease were diagnosed by histopathology as stage I. The accuracy for tumor free CRM was 86.5% (527/609) and the NPV was 98.1% (514/524). In 1.7% (9/524) mrMRF was false negative. CONCLUSION: MRI prediction of the tumor-free margin is more reliable than the prediction of tumor stage. MRF status as determined MRI should therefore be prioritized for decision making.

Avoidance of Overtreatment of Rectal Cancer by Selective Chemoradiotherapy: Results of the Optimized Surgery and MRI-Based Multimodal Therapy Trial.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) in patients with rectal cancer carries a high risk of adverse effects. The aim of this study was to examine the selective application of nCRT based on patient risk profile, as determined by MRI, to find the optimal range between undertreatment and overtreatment. STUDY DESIGN: In this prospective multicenter observational study, nCRT before total mesorectal excision (TME) was indicated in high-risk patients with involved or threatened mesorectal fascia (≤1 mm), or cT4 or cT3 carcinomas of the lower rectal third. All other patients received primary surgery. RESULTS: Of the 1,093 patients, 878 (80.3%) were treated according to the protocol, 526 patients (59.9%) underwent primary surgery, and 352 patients (40.1%) underwent nCRT followed by surgery. The 3-year locoregional recurrence (LR) rate was 3.1%. Of 604 patients with clinical stages II and III, 267 (44.2%) had primary surgery; 337 (55.8%) received nCRT followed by TME. The 3-year LR rate was 3.9%, without significant differences between groups. In patients with clinical stages II and III who underwent primary surgery, 27.3% were diagnosed with pathological stage I. CONCLUSIONS: The results justify the restriction of nCRT to high-risk patients with rectal cancer classified by pretreatment MRI. Provided that a high-quality MRI diagnosis, TME surgery, and standardized examination of the resected specimen are performed, nCRT, with its adverse effects, costs, and treatment time can be avoided in more than 40% of patients with stage II or III rectal cancer with minimal risk of undertreatment. (clinicaltrials.gov NCT325649).

MRI-Based Use of Neoadjuvant Chemoradiotherapy in Rectal Carcinoma: Surgical Quality and Histopathological Outcome of the OCUM Trial.

BACKGROUND: Preoperative magnetic resonance imaging (MRI) allows highly reliable imaging of the mesorectal fascia (mrMRF) and its relationship to the tumor. The prospective multicenter observational study OCUM uses these findings to indicate neoadjuvant chemoradiotherapy (nCRT) in rectal carcinoma. METHODS: nCRT was indicated in patients with positive mrMRF (≤ 1 mm) in cT4 and cT3 carcinomas of the lower rectal third. RESULTS: A total of 527 patients (60.2%) underwent primary total mesorectal excision, and 348 patients (39.8%) underwent long-term nCRT followed by surgery. The mrMRF was involved in 4.6% of the primary surgery group and 80.7% of the nCRT group. Rates of resections within the mesorectal plane (90.8%), sparing of pelvic nerves on both sides (97.8%), and number of regional lymph nodes (95.3% with ≥ 12 lymph nodes examined) are indicative of high-quality surgery. Resection was classified as R0 in 98.3%, the pathological circumferential resection margin (pCRM) was negative in 95.1%. Patients in the nCRT group had more advanced carcinomas with a significantly higher rate of abdominoperineal excision. Independent risk factors for pCRM positivity were advanced stage (T4), metastatic lymph nodes, resection in the muscularis propria plane, and location in the lower third. CONCLUSIONS: The risk classification of rectal cancer patients by MRI seems to be highly reliable and allows the restriction of nCRT to approximately half of the patients with clinical stage II and III rectal carcinoma, provided there is a high-quality MRI diagnostic protocol, high-quality surgery, and standardized examination of the resected specimen.

Local excision followed by early radical surgery in rectal cancer: long-term outcome.

BACKGROUND: In rectal cancers, radical surgery should follow local excisions, in cases of unexpected, unfavorable tumor characteristics. The oncological results of this completion surgery are inconsistent. This retrospective cohort study assessed the clinical and long-term oncological outcomes of patients that underwent completion surgery to clarify whether a local excision compromised the results of radical surgery. METHODS: Forty-six patients were included, and the reasons for completion surgery, intraoperative complications, residual tumors, local recurrences (LRs), distant metastases, and cancer-specific survival (CSS) were assessed. The results were compared to 583 patients that underwent primary surgery without adjuvant therapy, treated with a curative intention during the same time period. RESULTS: The median follow-up was 14.6 years. The reasons for undergoing completion surgery were positive resection margins (24%), high-risk cancer (30%), or both (46%). Intraoperative perforations occurred in 10/46 (22%) cases. Residual tumor in the rectal wall or lymph node involvement occurred in 12/46 (26%) cases. The risk of intraoperative perforation and residual tumor increased with the pT category. Intraoperative perforations did not increase postoperative complications, but they increased the risk of LRs in cases of intramural residual tumors (p = 0.003). LRs occurred in 2.6% of pT1/2 and 29% of pT3 tumors. Both the 5- and 10-year CSS rates were 88.8% (95% CI 80.0-98.6). Moreover, the LRs of patients with pT1/2 cancers were lower in patients with completion surgery than in patients with primary surgery. CONCLUSIONS: Rectal wall perforations at the local excision site and residual cancer were the main risks for poor oncological outcomes associated with completion surgery. Local excisions followed by early radical surgery did not appear to compromise outcomes compared to patients with primary surgery for pT1/2 rectal cancer. Improvements in clinical staging should allow more appropriate selection of patients that are eligible for a local excision of rectal cancer.

The Link Between Local Recurrence and Distant Metastases in Patients With Rectal Cancer.

BACKGROUND/AIM: The relationships between local recurrence (LR), the development of distant metastases (DM) and prognosis in patients with rectal cancer remain unclear. PATIENTS AND METHODS: In 606 patients who underwent curative resection, the role of LR was assessed retrospectively by time-dependent multivariate Cox models with inverse probability of treatment weighting taking into account competing risks. RESULTS: Patients with LR had more DM than patients without LR (49/79, 62% vs. 86/524, 16.4%; p<0.001); 37% of LR-associated DM developed before or at LR, 63% after diagnosis of LR. Fifty-five percent of patients without DM at diagnosis of LR later developed DM. In these patients, the incidence of DM significantly exceeded the incidence in patients without LR. DM risk was most strongly associated with preceding LR and stage UICC III and II. CONCLUSION: There is a causal link between LR and DM in patients with rectal cancer.

Analysis of local recurrences after transanal endoscopic microsurgery for low risk rectal carcinoma.

AIM: Rates of local recurrence (LR) after transanal endoscopic microsurgery (TEM) for rectal carcinoma vary; the reasons remain unclear. We analyzed LR after TEM for low-risk pT1 (G1/2/X, L0/X) rectal carcinoma to investigate the influence of completeness of resection and occult lymph node metastasis on risk of LR. METHOD: LR location and stage, completeness of resection of primary carcinoma (minimal distance between tumor and resection line ≤1 mm vs >1 mm), and incidence of involved lymph nodes in resected LR specimens were collected, and tumor characteristics of LR were compared with primary carcinoma. Distant metastasis and overall and cancer-specific survival were determined. RESULTS: LR developed in 14 patients; in 2/4 with R1/X resection, in 3/8 (38%) with clear margins (R0) but a minimal distance of ≤1 mm, and in 9/88 (10%) with formally complete resection. Six of nine patients with formally complete resection underwent radical surgery for LR; in five out of these six, lymph nodes were not involved. In 5/14 patients, LR was poorly differentiated compared to primary carcinoma. Main LR causes were incomplete tumor resection or tumor persistence after formally complete resection. Overall (p = 0.008) and cancer-specific (p < 0.001) survival was lower in LR patients compared to non-LR patients, even if lymph nodes were uninvolved. CONCLUSIONS: The results suggest that most LRs after TEM for low-risk rectal cancer were caused by residual tumor at the previous excision site and not by undetected lymph node metastases. By improved standardization of surgical techniques to ensure complete resection of carcinomas and thorough pathological assessments, most LRs seem to be avoidable.

Influence of Local Recurrence and Distant Metastasis on Prognosis After Local Excision of Rectal Carcinoma.

BACKGROUND: Influence of local recurrence (LR) on prognosis after a local excision (LE) for rectal cancer is unclear. PATIENTS AND METHODS: A total of 152 patients were retrospectively assigned to one of three groups: Groups 1 and 2: complete and incomplete resection respectively, for low-risk carcinoma; group 3: high-risk carcinoma. We evaluated LR, distant metastasis (DM), overall survival, and cancer-specific survival (CSS). RESULTS: LR rates were 10.4%, 43% and 29% for groups 1-3, respectively (p=0.002). In all three groups, DM incidence was low in patients without LR, but high in patients with LR (p<0.0001). Prior LR was an important risk factor for DM (hazard ratio: 14.1, 95% confidence interval=4.3-45.8, p<0.0001). DM significantly reduced CSS. CONCLUSION: There is a strong association between LR and DM independently in the cause of LR. Avoiding LE for high-risk carcinoma and complete LE of low-risk carcinoma are essential to reduce LR and DM.

Long-term Oncologic Outcome After Transanal Endoscopic Microsurgery for Rectal Carcinoma.

BACKGROUND: Transanal endoscopic microsurgery is superior to other methods of local excision of rectal cancer, but few studies report long-term follow-up data. OBJECTIVE: This study investigated the use of transanal endoscopic microsurgery alone as curative and compromise therapy based on long-term disease recurrence and mortality. DESIGN: This was a retrospective review of prospectively collected data. SETTINGS: The study was conducted at a tertiary care university medical center. PATIENTS: The study included 133 patients treated between 1985 and 2007. There were 3 groups, including transanal endoscopic microsurgery in curative intent (low-risk rectal carcinoma, including pT1, G1/2, L0, and LX with clear margins and a minimal distance between tumor and resection margin of >1 mm (N = 64) or clear margins only (N = 18 ))) and as compromise therapy (high-risk or incompletely resected rectal carcinoma; N = 51). MAIN OUTCOME MEASURES: Log-rank tests were used to compare overall and cancer-specific survival. RESULTS: The median follow-up time was 8.6 years (range, 0.2-25.1 years), and a total of 131 of 133 patients (98.5%) were followed >5 years or until death. The preoperative diagnosis of carcinoma was not associated with belonging into 1 of the 3 categories. In patients with low-risk completely (>1 mm) resected carcinoma, the 5- and 10-year local recurrence rates were 6.6% and 11.6%. In patients with high-risk or incompletely resected carcinoma, the rates were 32.5% and 35.0% (p = 0.006). The 5- and 10-year cancer-specific survival rates for low-risk patients were 98.0% and 91.0% and 84.3% and 74.3% for high-risk patients (p = 0.05). LIMITATIONS: The study was limited by its retrospective design and small subgroups. CONCLUSIONS: The high cancer-specific survival justifies transanal endoscopic microsurgery alone as curative treatment in low-risk rectal carcinoma. Complete resection is essential to lower the risk of local recurrence. The high local recurrence rate in patients with high-risk rectal carcinoma restricts the use of TEM alone as compromise therapy.

Rectal cancer: dynamic contrast-enhanced MRI correlates with lymph node status and epidermal growth factor receptor expression.

PURPOSE: To evaluate correlations between dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and clinicopathologic data as well as immunostaining of the markers of angiogenesis epidermal growth factor receptor (EGFR) and CXC-motif chemokine receptor 4 (CXCR4) in patients with rectal cancer. MATERIALS AND METHODS: Presurgical DCE-MRI was performed in 41 patients according to a standardized protocol. Two quantitative parameters (k21 , A) were derived from a pharmacokinetic two-compartment model, and one semiquantitative parameter (TTP) was assessed. Standardized surgery and histopathologic examinations were performed in all patients. Immunostaining for EGFR and CXCR4 was performed and evaluated with a standardized scoring system. RESULTS: DCE-MRI parameter A correlated significantly with the N category (P = 0.048) and k21 with the occurrence of synchronous and metachronous distant metastases (P = 0.029). A trend was shown toward a correlation between k21 and EGFR expression (P = 0.107). A significant correlation was found between DCE-MRI parameter TTP and the expression of EGFR (P = 0.044). DCE-MRI data did not correlate with CXCR4 expression. CONCLUSION: DCE-MRI is a noninvasive method which can characterize microcirculation in rectal cancer and correlates with EGFR expression. Given the relationship between the dynamic parameters and the clinicopathologic data, DCE-MRI data may constitute a prognostic indicator for lymph node and distant metastases in patients with rectal cancer.

pT2 Adenocarcinoma of the esophagus: early or advanced cancer?

BACKGROUND: There is an increasing trend to include patients with esophageal carcinoma invading the muscularis propria (pT2) in neoadjuvant therapy regimens. But it is unclear which patients have prognostic benefit from this strategy. The aim of this study was to assess the prognosis and prognostic factors in patients with pT2 esophageal adenocarcinoma to further optimize treatment strategies. METHODS: Included were patients with pT2 esophageal adenocarcinoma treated operatively at three centers specializing in upper gastrointestinal surgery. There were 159 patients (139 male) without induction therapy; median age was 64.5 years. Survival was analyzed by univariate and multivariate analysis. RESULTS: In 37% of patients (n = 59), no lymph node involvement (pN0) was detected. Overall 5-year survival rate for all patients was 37%; for pN0 patients it was 62%, and for patients with lymph node metastases (pN+) it was 24%. Median number of examined lymph nodes was 26. Extracapsular lymph node involvement (ELNI) was evident in 55 of 100 pN+ patients with a 5-year survival rate of 14%. Patients without ELNI had a 5-year survival rate of 36% (p = 0.041). Results were comparable in all participating hospitals. Thirty-day and 90-day mortality rates of the entire collective were 2.6% and 3.8%, respectively. Multivariate analysis of prognosis revealed the lymph node ratio (p < 0.001) and the pN-ELNI category (p = 0.005) as significant parameters (pN0 hazard ratio 1 [reference]; pN+ without ELNI hazard ratio 2.2, 95% confidence interval: 1.2 to 3.8); pN+ with ELNI hazard ratio 2.5, 95% confidence interval: 1.5 to 4.5). CONCLUSIONS: The prognosis of patients with esophageal adenocarcinoma invading the muscularis propria without lymph node metastasis is very good. However, in this study, about 30% had extracapsular lymph node involvement, which reflects particularly aggressive biological tumor behavior.

Prognostic scoring system predictive of survival after surgical resection of esophageal carcinoma.

BACKGROUND: The aim of our study was to develop a prognostic index score for patients undergoing surgical resection for esophageal cancer that accurately determines survival with specific clinicopathological characteristics. METHODS: Clinical, histological, and demographical variables of 475 patients were entered in an univariate and multivariate regression model, followed by individual calculation of the Prognostic Indicator Score and model validation via simulation. RESULTS: Significant variables included in the scoring system were number of positive lymph nodes, pT, pL, R, obesity, and American Society of Anesthesiologist classification. Survival probability and its associated hazard function was significantly different between the scores, with an increase of hazard ratio ranging from 2.56 (score 2) to 20 (score 6 or higher). Comparing histological cancer entities revealed statistical significance only between stage IIA versus IIB in squamous cell and stage IIIA versus IIIB in adenocarcinoma. CONCLUSIONS: According to our methodology, an individualized follow-up by each possible score might allow interdisciplinary selection of patients for treatments based on expected survival. This may represent a breakthrough in patient selection for currently available treatments and clinical studies.

Pretherapeutic MRI for decision-making regarding selective neoadjuvant radiochemotherapy for rectal carcinoma: interim analysis of a multicentric prospective observational study.

PURPOSE: To study the accuracy of different cutoffs for an involved circumferential resection margin (CRM) compared with T and N categories measured by MRI as basis for selective application of neoadjuvant radiochemotherapy (nRCT) in rectal carcinoma. MATERIALS AND METHODS: In a prospective multicenter observational study involving 153 primarily operated patients, the preoperative results of MRI with pathohistological findings of resected specimens were compared. RESULTS: For a cutoff of ≤1 mm for involvement of the CRM, the accuracy of preoperative MRI was 90.9% (139/153). The negative predictive value was 98.5% (134/136). The four participating departments did not differ significantly. For a cutoff of >2 mm and >5 mm, the rates of false-positive findings increased significantly from 5% to 12% and 35% with a decrease in accuracy to 82% and 62%, respectively. In contrast, the accuracy in predicting T (69.3%) and N categories (61.4%) was much lower. CONCLUSION: The indication for nRCT should be based on the determination of the minimal distance of the tumor from mesorectal fascia with a cutoff point of >1 mm as measured by MRI.

Cause of death during long-term follow-up for superficial esophageal adenocarcinoma.

BACKGROUND: The purpose of this study was to evaluate long-term prognosis and cause of death in patients with superficial esophageal adenocarcinoma (SEAC) after surgery. PATIENTS AND METHODS: A total of 85 patients without adjuvant or neoadjuvant treatment underwent surgery for SEAC (pT1N0-1, M0) 1984-2011. Medical records and causes of death were reviewed, and 79 specimens (93 %) were reanalyzed for cancer penetration. Survival was calculated according to Kaplan-Meier and comparisons of survival with log-rank test. Multivariate survival was analyzed with Cox proportional hazards model. RESULTS: Of 85 patients, 36 had transhiatal, 33 transthoracic en bloc, 6 minimally invasive en bloc, 5 vagal sparing esophageal resection and 5 endoscopic mucosal resections; 7 patients (8 %) had lymph node metastasis (LNM). Cancer penetration: 35 pT1a and 44 pT1b. Overall survival was 67 % at 5 years and 50 % at 10 years. Disease-specific survival was 82 % at 5 years and 78 % at 10 years. Recurrence-free survival was 80 % at 5 years. In a Cox multivariate model, poor overall survival was predicted only by LNM. Cumulative mortality during median follow-up of 5 years (0-25 years): 37 of 85 (44 %). Cause of death of these 37: SEAC recurrence for 15 (41 %), postoperative complications for 4 (11 %), another primary malignancy for 5 (14 %), non-cancer-related for 11 (30 %) and for 2 (5 %) cause unknown. Mortality after 5-year follow-up: 11 (30 %); 82 % of these deaths were unrelated to SEAC recurrence. CONCLUSIONS: With SEAC recurrence as the single most common cause of death, disease-specific 5-year survival was good. Overall and late (> 5-year) survival is affected by diseases related to aging.

Rectal cancer: assessment of response to neoadjuvant chemoradiation by dynamic contrast-enhanced MRI.

PURPOSE: To assess pretreatment functional and morphological tumor characteristics with magnetic resonance imaging (MRI) in advanced rectal carcinoma and to identify factors predicting response to neoadjuvant chemoradiation. MATERIALS AND METHODS: In a prospective study, 95 patients with rectal carcinoma underwent dynamic contrast-enhanced MRI before and after chemoradiation. Quantitative parameters were derived from a pharmacokinetic two-compartment model. Tumors were also characterized with regard to mucinous status at pretreatment high-resolution MRI as nonmucinous or mucinous. Response to treatment was defined as a downshift in the local tumor stage. RESULTS: The parameter k21 (contrast medium exchange rate) was higher at pretreatment MRI in nonmucinous compared with mucinous carcinomas (P < 0.001). The effect of chemoradiation on dynamic MR parameters was higher in nonmucinous carcinomas than in the mucinous subtype (P < 0.001). A higher rate of response to treatment was linked with nonmucinous morphology (P < 0.001). Multivariate analysis revealed an association between mucinous tumor morphology and poor response (odds ratio [95% confidence interval]: 0.113 [0.032-0.395], P < 0.001) as well as an association between a high 75th percentile of k21 and a higher response rate (odds ratio: 1.043 [1.001-1.086], P = 0.019). CONCLUSION: Functional and morphological parameters of pretreatment MRI can assess tumor characteristics associated with the effectiveness of chemoradiation before treatment initiation.

Rectal Cancer: MR imaging of the mesorectal fascia and effect of chemoradiation on assessment of tumor involvement.

PURPOSE: To evaluate the impact of chemoradiation on the reliability of MRI in assessing tumor involvement of the mesorectal fascia in patients with rectal cancer. MATERIALS AND METHODS: Presurgical MRI was performed in 150 patients; among them 85 had received neoadjuvant long-course chemoradiation. A standardized imaging protocol (1.5 Tesla [T] system, image voxel size 0.6 × 0.4 × 3 mm(3) ), standardized surgery, and histopathological examination were applied for the entire patient population. Images were analyzed to identify potential tumor involvement of the mesorectal fascia (minimum tumor distance to fascia ≤1 mm) and compared with histopathology as the reference standard. Results of nonirradiated and irradiated patients were compared to define the impact of chemoradiation on imaging reliability. RESULTS: In nonirradiated patients, MRI was reliable in predicting or excluding tumor involvement of the mesorectal fascia, positive predictive value 80%, negative predictive value 89%. The frequency of overestimating tumor involvement was significantly higher in irradiated patients (P = 0.005, positive predictive value 42%). CONCLUSION: Discussions about MRI assessment of tumor involvement of the mesorectal fascia as a basis for recommending neoadjuvant chemoradiation should focus on investigations that excluded irradiated patients, because MRI is less reliable after chemoradiation and tends to overestimate mesorectal tumor involvement.

Survival after chemotherapy and/or radiotherapy versus self-expanding metal stent insertion in the setting of inoperable esophageal cancer: a case-control study.

BACKGROUND: Our aim was to compare survival of the various treatment modality groups of chemotherapy and/or radiotherapy in relation to SEMS (self-expanding metal stents) in a retrospective case-control study. We have made the hypothesis that the administration of combined chemoradiotherapy improves survival in inoperable esophageal cancer patients. METHODS: All patients were confirmed histologically as having surgically non- resectable esophageal carcinoma. Included were patients with squamous cell carcinoma, undifferentiated carcinoma as well as Siewert type I--but not type II - esophagogastric junctional adenocarcinoma. The decision to proceed with palliative treatments was taken within the context of a multidisciplinary team meeting and full expert review based on patient's wish, co-morbid disease, clinical metastases, distant metastases, M1 nodal metastases, T4-tumor airway, aorta, main stem bronchi, cardiac invasion, and peritoneal disease. Patients not fit enough to tolerate a radical course of definitive chemo- and/or radiation therapy were referred for self-expanding metal stent insertion. Our approach to deal with potential confounders was to match subjects according to their clinical characteristics (contraindications for surgery) and tumor stage according to diagnostic work-up in four groups: SEMS group (A), Chemotherapy group (B), Radiotherapy group (C), and Chemoradiotherapy group (D). RESULTS: Esophagectomy was contraindicated in 155 (35.5%) out of 437 patients presenting with esophageal cancer to the Department of General and Abdominal Surgery of the University Hospital of Mainz, Germany, between November 1997 and November 2007. There were 133 males and 22 females with a median age of 64.3 (43-88) years. Out of 155 patients, 123 were assigned to four groups: SEMS group (A) n = 26, Chemotherapy group (B) n = 12, Radiotherapy group (C) n = 23 and Chemoradiotherapy group (D) n = 62. Mean patient survival for the 4 groups was as follows: Group A: 6.92 ± 8.4 months; Group B: 7.75 ± 6.6 months; Group C: 8.56 ± 9.5 months, and Group D: 13.53 ± 14.7 months. Significant differences in overall survival were associated with tumor histology (P = 0.027), tumor localization (P = 0.019), and type of therapy (P = 0.005), respectively, in univariate analysis. Treatment modality (P = 0.043) was the only independent predictor of survival in multivariate analysis. The difference in overall survival between Group A and Group D was highly significant (P < 0.01) and in favor of Group D. As concerns Group D versus Group B and Group D versus Group C there was a trend towards a difference in overall survival in favor of Group D (P = 0.069 and P = 0.059, respectively). CONCLUSIONS: The prognosis of inoperable esophageal cancer seems to be highly dependent on the suitability of the induction of patient-specific therapeutic measures and is significantly better, when chemoradiotherapy is applied.

Rectal cancer: mucinous carcinoma on magnetic resonance imaging indicates poor response to neoadjuvant chemoradiation.

PURPOSE: To assess response of locally advanced rectal carcinoma to chemoradiation with regard to mucinous status and local tumor invasion found at pretherapeutic magnetic resonance imaging (MRI). METHODS AND MATERIALS: A total of 88 patients were included in this prospective study of patients with advanced mrT3 and mrT4 carcinomas. Carcinomas were categorized by MRI as mucinous (mucin proportion >50% within the tumor volume), and as nonmucinous. Patients received neoadjuvant chemoradiation consisting of 50.4 Gy (1.8 Gy/fraction) and 5-fluorouracil on Days 1 to 5 and Days 29 to 33. Therapy response was assessed by comparing pretherapeutic MRI with histopathology of surgical specimens (minimum distance between outer tumor edge and circumferential resection margin = CRM, T, and N category). RESULTS: A mucinous carcinoma was found in 21 of 88 patients. Pretherapeutic mrCRM was 0 mm (median) in the mucinous and nonmucinous group. Of the 88 patients, 83 underwent surgery with tumor resection. The ypCRM (mm) at histopathology was significantly lower in mucinous carcinomas than in nonmucinous carcinomas (p ≤ 0.001). Positive resection margins (ypCRM ≤ 1 mm) were found more frequently in mucinous carcinomas than in nonmucinous ones (p ≤ 0.001). Treatment had less effect on local tumor stage in mucinous carcinomas than in nonmucinous carcinomas (for T downsizing, p = 0.012; for N downstaging, p = 0.007). Disease progression was observed only in patients with mucinous carcinomas (n = 5). CONCLUSION: Mucinous status at pretherapeutic MRI was associated with a noticeably worse response to chemoradiation and should be assessed by MRI in addition to local tumor staging to estimate response to treatment before it is initiated.

MRI-based indications for neoadjuvant radiochemotherapy in rectal carcinoma: interim results of a prospective multicenter observational study.

BACKGROUND: This study evaluated use of circumferential resection margin status in preoperative MRI (mrCRM) as an indication for neoadjuvant radiochemotherapy (nRCT) in rectal carcinoma patients. MATERIALS AND METHODS: In a multicenter prospective study, nRCT was given to patients with carcinoma of the middle rectum with positive mrCRM (≤1 mm), with cT3 low rectal carcinoma, and all patients with cT4 tumors. The short-term endpoints were pathologic pCRM (≤1 mm) as a strong predictor of local recurrence rate and the quality of total mesorectal excision according to the plane of surgery. These endpoints were compared in patients with and without nRCT. RESULTS: Of 230 patients that met the inclusion criteria, 96 (41.7%) received a long course of nRCT and 134 (58.3%) were primarily operated on. The pCRM was positive in 13 of 230 (5.7%) (primarily operated on, 2 of 134 [1.5%]; after nRCT, 11 of 96 [11%]). In 1 of 134 (0.7%) case, the mrCRM was falsely negative. Patients at participating centers varied in terms of preoperative stage but not in pCRM positivity (0%-13%, P = .340). The plane of surgery was mesorectal (good) in 209 of 230 (90.9%), intramesorectal (moderate) in 16 of 230 (7%), and the muscularis propria plane (poor) in 2.2% (5 of 230). CONCLUSIONS: Low pCRM positivity and the high quality of mesorectal excision support use of MRI-based nRCT in rectal carcinoma. nRCT was avoidable in 45% of patients with stage II and III disease without significant risk of undertreatment. Preoperative MRI thus allows identification of patients with high risk of local recurrence and use of selective nRCT.