Seventh Edition (2010) of the AJCC/UICC Staging System for Gastric Adenocarcinoma: Is there Room for Improvement?

Background

The gastric cancer AJCC/UICC staging system recently underwent significant revisions, but studies on Asian patients have reported a lack of adequate discrimination between various consecutive stages. We sought to validate the new system on a U.S. population database.

Methods

California Cancer Registry data linked to the Office of Statewide Health Planning and Development discharge abstracts were used to identify patients with gastric adenocarcinoma (esophagogastric junction and gastric cardia tumors excluded) who underwent curative-intent surgical resection in California from 2002 to 2006. AJCC/UICC stage was recalculated based on the latest seventh edition. Overall survival probabilities were calculated using the Kaplan–Meier method.

Results

Of 1905 patients analyzed, 54 % were males with a median age of 70 years. Median number of pathologically examined lymph nodes was 12 (range, 1–90); 40 % of patients received adjuvant chemotherapy, and 31 % received adjuvant radiotherapy. The seventh edition AJCC/UICC system did not distinguish outcome adequately between stages IB and IIA (P = 0.40), or IIB and IIIA (P = 0.34). By merging stage II into 1 category and moving T2N1 to stage IB and T2N2, T1N3 to stage IIIA, we propose a new grouping system with improved discriminatory ability

Conclusions

In this first study validating the new seventh edition AJCC/UICC staging system for gastric cancer on a U.S. population with a relatively limited number of lymph nodes examined, we found stages IB and IIA, as well as IIB and IIIA to perform similarly. We propose a revised stage grouping for the AJCC/UICC staging system that better discriminates between outcomes.     

Endoscopic Ultrasound Staging of Stenotic Esophageal Cancers May Be Unnecessary to Determine the Need for Neoadjuvant Therapy

Introduction

Endoscopic ultrasound (EUS) is an essential component of preoperative staging for esophageal cancer and is used to determine which patients should proceed to primary surgical resection or receive neoadjuvant therapy prior to surgery. However, when the EUS scope cannot traverse a tumor, the role of pre-dilatation is controversial due to the risk of perforation.

Methods

A retrospective review was conducted of all patients with esophageal tumor stenosis that could not accommodate the EUS scope who then proceeded with primary esophagectomy. The pathology results were classified based on the revised seventh edition American Joint Committee on Cancer staging system.

Results

A total of 27 patients met inclusion criteria. The majority of tumors were T3 (24/27, 89 %). There were no stage I tumors, 15 % (4/27) were stage II, 81 % (22/27) were stage III, and 4 % (1/27) were stage IV due to a resected solitary lung metastasis.

Conclusion

Tumors that cannot be assessed with an EUS scope due to tumor stenosis will have locally advanced disease in the majority of cases. In these situations, pre-dilatation of the tumor with EUS staging should be omitted when considering the risk of potential esophageal perforation and the patients should be referred for neoadjuvant therapy.     

Influence of Treatment Modality in Outcomes for Different Stages of Resectable Esophageal Adenocarcinomas

Background

There is no consensus on the most effective modality for the treatment of resectable esophageal adenocarcinomas (EAC). We theorized that treatment modality may influence survival differently depending on the stage of disease.

Methods

A single-institution, retrospective examination of resectable EAC between 2000 and 2008 was performed. Resectable EAC were stratified into early disease (stage 2a or less) and late disease (stage 2b or more) based on pretreatment endoscopic ultrasound (EUS). Patients with T4, >N2, and/or distant disease were excluded.

Results

A total of 156 patients were included in this study. Most patients were white (97 %), male (83 %), and over 60 years of age (51 %). Patients with early disease on pretreatment EUS exhibited improved overall survival compared to patients with late disease (P < 0.001). Irrespective of treatment modality, there were no significant differences in overall 5-year survival for patients with early or late disease. Early and late disease patients whose disease responded to neoadjuvant chemotherapy (NAC) had significantly improved overall survival compared to nonresponsive disease (P < 0.05). The only negative independent predictors of overall 5-year survival were late stage disease on pretreatment EUS (hazard ratio 2.402, 95 % confidence interval 1.24–4.67, P = 0.01) and late stage disease on final pathological stage (hazard ratio 2.29, 95 % confidence interval 1.22–4.31, P = 0.01).

Conclusions

Our data lack statistical power but reveal no difference in survival with the addition of neoadjuvant therapies to surgery for early or late resectable EAC. However, patients with disease that responded to NAC had improved outcomes at 5 years for both groups. Therefore, the prognosis for patients undergoing NAC may be optimized by immediate surgical resection if neoadjuvant therapies do not result in a dramatic clinical response.     

Treatment of Clinical T2N0M0 Esophageal Cancer

Background

Management of clinical T2N0M0 (cT2N0M0) esophageal cancer remains controversial. We reviewed our institutional experience over 21 years (1990–2011) to determine clinical staging accuracy, optimal treatment approaches, and factors predictive of survival in this patient population.

Methods

Patients with cT2N0M0 esophageal cancer determined by endoscopic ultrasound (EUS) were identified through a prospectively collected database. Demographics, perioperative data, and outcomes were examined. Cox regression model and Kaplan–Meier plots were used for statistical survival analysis.

Results

A total of 731 patients underwent esophagectomy, of whom 68 cT2N0M0 patients (9 %) were identified. Fifty-seven patients (84 %) had adenocarcinoma. Thirty-three patients (48.5 %) were treated with neoadjuvant chemoradiation followed by surgery, and 35 underwent surgical resection alone. All resections except one included a transthoracic approach with two-field lymph node dissection. Thirty-day operative mortality was 2.9 %. Only 3 patients (8.5 %) who underwent surgery alone had T2N0M0 disease identified by pathology: the disease of 15 (42.8 %) was found to be overstaged and 17 (48.5 %) understaged after surgery. Understaging was more common in poorly differentiated tumors (p = 0.03). Nine patients (27.2 %) had complete pathologic response after chemoradiotherapy. Absence of lymph node metastases (pN0) was significantly more frequent in the neoadjuvant group (29 of 33 vs. 21 of 35, p = 0.01). Median follow-up was 44.2 months. Overall 5-year survival was 50.8 %. On multivariate analysis, adenocarcinoma (p = 0.001) and pN0 after resection (p = 0.01) were significant predictors of survival.

Conclusions

EUS was inaccurate in staging cT2N0M0 esophageal cancer in this study. Poorly differentiated tumors were more frequently understaged. Adenocarcinoma and absence of lymph node metastases (pN0) were independently predictive of long-term survival. pN0 status was significantly more common in patients undergoing neoadjuvant therapy, but long-term survival was not affected by neoadjuvant therapy. A strategy of neoadjuvant therapy followed by resection may be optimal in this group, especially in patients with disease likely to be understaged.     

A Comparison of Five Competing Lymph Node Staging Schemes in a Cohort of Resectable Gastric Cancer Patients

Background

New classifications for lymph node (LN) staging have recently been proposed to improve upon the UICC/AJCC N category staging convention. Ratio-based systems and logarithmic odds (LODDS) scores are two families of novel competing staging systems. We compared UICC/AJCC staging with 5 ratio and LODDS systems in predicting overall survival (OS) in patients with resected gastric cancer.

Methods

Using a large population-based dataset, we identified 12,184 nonmetastatic resectable gastric cancer patients between 1988 and 2004. We compared each subject’s UICC/AJCC N stage with five novel staging schemes. We analyzed the OS for each method. Our comparison metric was the log-rank Chi squared statistic; larger Chi squared statistics indicate improvements in N stage discrimination.

Results

Median OS was 2.1 years (95 % CI 2.0–2.2 years), while median patient follow-up for surviving patients was 8.3 years (range, 1 month–22 years). Although all 5 staging systems were either comparable or superior to the UICC/AJCC convention, a LN ratio method outperformed others in N stage discrimination based on log-rank tests for OS. This trend was independent of the number of LNs examined.

Conclusions

Novel LN staging methods have a higher degree of discrimination utility than the UICC/AJCC N convention. These methods may have a role in reducing the prognostic impact of LN count variability. Of the systems assessed, the LN ratio system that assigns greater risk attribution to cases with <16 LNs was the best classification method to predict OS in patients with resectable gastric cancer.     

Appraisal of Staging Endoscopic Ultrasonography in a Modern High-Volume Esophageal Program

Background

Accurate pretreatment staging is essential to decision making for patients with esophageal and junctional cancers, particularly when choosing endoscopic therapy or a multimodal approach. As the efficacy of endoscopic ultrasonography (EUS) has been reported as variable, we assessed it prospectively in a large cohort from a high-volume center.

Methods

The EUS data from 2007 to 2011 were reviewed and analyzed. We conducted a comparative analysis with computed tomography-positron emission tomography (CT-PET) staging and pathology. Survival was analyzed by Kaplan–Meier testing on EUS-predicted T- and N-stage cohorts.

Results

Altogether, 222 patients underwent EUS. Among patients undergoing primary surgical resection, preoperative EUS diagnosed the T stage correctly in 71 % (55/77) of cases. Sensitivity and specificity for T1, T2, and T3 tumors were 94 and 89 %, 55 and 80 %, and 66 and 93 %, respectively. Mean maximum standard uptake volume on CT-PET correlated moderately with the EUS T stage (r = 0.42, p < 0.0001). EUS accuracy for nodal disease was 65 %. Survival was statistically better for the EUS T1 group than for those with T3 tumors (p = 0.01). Nodal metastases diagnosed on EUS predicted a significantly worse prognosis than EUS-negative nodes on both univariate and multivariate analyses (p < 0.0001 and p = 0.005 respectively).

Conclusions

There was a significant relation between EUS T and N stages and overall survival. EUS demonstrated 71 % accuracy for the overall T stage. Staging accuracy of EUS for large lesions was less effective than for T1 tumors, underlining the need for a multimodal investigative approach to stage esophageal tumors accurately.     

Miniprobe endoscopic ultrasound accurately stages esophageal cancer and guides therapeutic decisions in the era of neoadjuvant therapy: results of a multicenter cohort analysis

Background

Despite recent advances in imaging techniques, adequate classification of esophageal lesions is still challenging. Accurate staging of tumors of the esophagus is a precondition for targeted therapy. In this retrospective, multicenter study, we report the role of high-frequency endoscopic ultrasound (EUS) catheter probes in pretherapeutic staging of esophageal neoplasms and thus guiding treatment decisions.

Methods

A total of 143 patients (mean age of 63.8 ± 10.7 years) with esophageal carcinoma were recruited from five German centers (Münster, Oldenburg, Hannover, Wiesbaden, and Lüneburg). Tumor type was adenocarcinoma in 112 (78 %) cases and squamous cell carcinoma in 31 (22 %). Tumor localization was as follows: proximal 3, mid esophagus 7, and distal third 133. Histological correlation either through EMR or surgery was available. In all patients, pretherapeutic uT and uN classifications were compared to pT/pN classification obtained from surgically (esophagectomy, n = 93) or endoscopically (EMR, n = 50) resected tissue.

Results

Overall, accuracy of uT classification was 60 % and of uN classification was 74 %. Sensitivity, specificity, and accuracy rates for local tumor extension were as follows (%): T1: 68/97/83; T2: 39/84/75; T3: 72/81/79; T4: 13/97/93; T1/2: 73/81/75; T3/4: 78/82/81. Relating to positive lymph node detection, sensitivity and specificity were 76 and 71 %, respectively.

Conclusions

Miniprobe EUS is an established method for the staging of esophageal tumors. Our large multicenter cohort shows a solid accuracy of miniprobe EUS with respect to differentiating locally advanced from limited cancer and assisting to determine the treatment regimen in the era of neoadjuvant therapy; consequently, 78 % of patients would have been assigned to the adequate therapeutic regimen, whereas 11 % of patients would have been overtreated and 11 % undertreated.     

Induction of a Pathological Complete Response by Four Courses of Neoadjuvant Chemotherapy for Gastric Cancer: Early Results of the Randomized Phase II COMPASS Trial

Background

The prognosis for stage 3 gastric cancer is not satisfactory, even with S-1 adjuvant chemotherapy. A randomized phase II trial was conducted to compare two and four courses of neoadjuvant S-1/cisplatin (SC) and paclitaxel/cisplatin (PC) using a two-by-two factorial design for locally advanced gastric cancer. The primary endpoint was overall survival. We clarified the impact of these regimens on the secondary endpoints, including the clinical and pathological responses, chemotherapy-related toxicities, and surgical results.

Methods

Patients received S-1 (80 mg/m² for 21 days with 1 week’s rest)/cisplatin (60 mg/m² at day 8) or paclitaxel/cisplatin (80 and 25 mg/m², respectively, on days 1, 8, and 15 with 1 week’s rest) as neoadjuvant chemotherapy.

Results

Eighty-three patients were assigned to arm A (two courses of SC, n = 21), arm B (four courses of SC, n = 20), arm C (two courses of PC, n = 21), and arm D (four courses of PC, n = 21). Pathological response rate was 43 % in arm A, 40 % in arm B, 29 % in arm C, and 38 % in arm D. Pathological complete response was only observed in arms B (10 %) and D (10 %). Most bone marrow toxicities, nausea, vomiting, alopecia, and fatigue were slightly higher but acceptable in arms B and D. Grade 3/4 surgical morbidities were not commonly observed in all four arms.

Conclusions

Pathological complete response could be induced by four courses of neoadjuvant chemotherapy without a marked increase of toxicities, regardless of a SC or PC regimen.     

A Multifactorial Histopathologic Score for the Prediction of Prognosis of Resected Esophageal Adenocarcinomas After Neoadjuvant Chemotherapy

Background

For esophageal adenocarcinoma treated with neoadjuvant chemotherapy, postoperative staging classifications initially developed for non-pretreated tumors may not accurately predict prognosis. We tested whether a multifactorial TNM-based histopathologic prognostic score (PRSC), which additionally applies to tumor regression, may improve estimation of prognosis compared with the current Union for International Cancer Control/American Joint Committee on Cancer (UICC) staging system.

Patients and Methods

We evaluated esophageal adenocarcinoma specimens following cis/oxaliplatin-based therapy from two separate centers (center 1: n = 280; and center 2: n = 80). For the PRSC, each factor was assigned a value from 1 to 2 (ypT0-2 = 1 point; ypT3-4 = 2 points; ypN0 = 1 point; ypN1-3 = 2 points; ≤50 % residual tumor/tumor bed = 1 point; >50 % residual tumor/tumor bed = 2 points). The three-tiered PRSC was based on the sum value of these factors (group A: 3; group B: 4–5; group C: 6) and was correlated with patients’ overall survival (OS).

Results

The PRSC groups showed significant differences with respect to OS (p < 0.0001; hazard ratio [HR] 2.2 [95 % CI 1.7–2.8]), which could also be demonstrated in both cohorts separately (center 1 p < 0.0001; HR 2.48 [95 % CI 1.8–3.3] and center 2 p = 0.015; HR 1.7 [95 % CI 1.1–2.6]). Moreover, the PRSC showed a more accurate prognostic discrimination than the current UICC staging system (p < 0.0001; HR 1.15 [95 % CI 1.1–1.2]), and assessment of two goodness-of-fit criteria (Akaike Information Criterion and Schwarz Bayesian Information Criterion) clearly supported the superiority of PRSC over the UICC staging.

Conclusion

The proposed PRSC clearly identifies three subgroups with different outcomes and may be more helpful for guiding further therapeutic decisions than the UICC staging system.     

Prognostic significance of endoscopic ultrasound-defined pleural, pericardial or peritoneal fluid in oesophageal cancer

Background

Endoscopic ultrasound (EUS) is known to detect smaller effusion volumes than computerised tomography (CT), yet the outcomes for patients diagnosed with oesophageal carcinoma and EUS-defined pleural, pericardial or ascitic fluid effusions (EDFE) are unknown. The aim of this study was to determine the outcome of multidisciplinary stage directed treatment for such patients.

Methods

Forty-nine (9.2%) out of a consecutive 527 patients diagnosed with oesophageal cancer from a single regional upper gastrointestinal (GI) cancer network were found to have evidence of EDFE undetected by CT. Thirty-nine (79.6%) patients had pleural effusions, eight (16.3%) pericardial effusions, and two (4.1%) ascites.

Results

Twelve (24.4%) underwent surgery, 3 (6.1%) received neoadjuvant chemotherapy without subsequent surgery, 12 (24.5%) received definitive chemoradiotherapy (dCRT), and 22 (44.9%) received palliative treatment. Survival in patients with EDFE was significantly shorter (median and 2-year survival 15.6 months and 24%, respectively) when compared with patients without EDFE (26.7 months and 40%, respectively, p = 0.001), and was unrelated to EDFE type (p = 0.192). Two-year survival after oesophagectomy with or without neoadjuvant therapy was 45% in patients with EDFE compared with 42% in patients without EDFE (p = 0.668).

Conclusions

EDFE was an important adverse prognostic indicator, but patients deemed to have operable tumours should still be treated with radical intent.     

Endoscopic Ultrasound in Staging Esophageal Cancer After Neoadjuvant Chemotherapy—Results of a Multicenter Cohort Analysis

Background

Endoscopic ultrasound (EUS) is considered a gold standard in the initial staging of esophageal cancer. There is an ongoing debate whether EUS is useful for tumor staging after neoadjuvant chemotherapy (NAC).

Methods

Ninety-five patients with esophageal cancer were retrospectively analyzed. In 45 patients, EUS was performed prior to and after NAC, while 50 patients had no induction therapy. Histological correlation through surgery was available. uT/uN classifications were compared to pT/pN stages. Statistical analysis included calculation of sensitivity, specificity, and accuracy rates. Agreement between endosonography and T staging was assessed with Cohen's kappa statistics.

Results

For those patients with prior NAC, overall accuracy of yuT and yuN classification was 29 and 62%, respectively. Sensitivity, specificity, and accuracy rates for local tumor extension after NAC were as follows (%): T1: –/97/84, T2: 13/76/53, T3:86/29/46, T4:20/100/91, T1/2: 27/83/56, T3/4: 89/31/56. Cohen's kappa indicated poor agreement (kappa?=?0.129) between yuT classification and ypT stage. Relative to positive lymph node detection, sensitivity and specificity were 100 and 6%, respectively (kappa?=?0.06). T stage was overstaged in 23 (51%) and understaged in seven (16%) patients.

Conclusion

EUS is an unreliable tool for staging esophageal cancer after NAC. Overstaging of the T stage is common after NAC.     

Prognostic Factors After Surgical Resection for Intrahepatic, Hilar, and Distal Cholangiocarcinoma

Background

The prognosis of patients with cholangiocarcinoma is unsatisfactory. Therefore, evaluation of prognostic factors and establishment of new therapeutic strategies are needed to improve their long-term survival. The aim of this study was to identify useful prognostic factors for patients with intrahepatic, hilar, and distal cholangiocarcinoma.

Materials and Methods

Records of 127 patients with cholangiocarcinoma (21 with intrahepatic cholangiocarcinoma, 50 with hilar cholangiocarcinoma, and 56 with distal cholangiocarcinoma) who underwent surgical resection were reviewed retrospectively. Relationships between survival and clinicopathological factors including patient demographics and tumor characteristics were evaluated using univariate and multivariate analysis.

Results

For all 127 patients, overall 1-, 3-, 5-year survival rates were 80, 51, and 40%, respectively. Univariate analysis revealed that adjuvant chemotherapy (P = .049), tumor differentiation (P = .014), lymph node metastasis (P < .001), surgical margin status (P < .001), UICC pT factor (P < .001), and UICC stage (P < .001) were associated significantly with survival. UICC pT factor (P = .007), adjuvant chemotherapy (P = .009), surgical margin status (P = .012), and lymph node metastasis (P = .014) remained independently associated with long-term survival by multivariate analysis. The 5-year survival rates of patients with or without positive surgical margins were 13 and 49%, respectively. The 5-year survival rates of patients treated with or without adjuvant chemotherapy were 47 and 36%, respectively.

Conclusions

R0 resection and adjuvant chemotherapy may be mandatory to achieve long-term survival for patients with cholangiocarcinoma.     

Factors Influencing the Long-Term Survival in Patients with Esophageal Cancer Who Underwent Esophagectomy After Chemoradiotherapy

Background

Salvage esophagectomy is potentially the only treatment available that can offer a chance of long-term survival when definitive chemoradiotherapy (CRT) fails to achieve local control for patients with esophageal squamous cell carcinoma (ESCC). However, salvage esophagectomy is a highly invasive procedure with various postoperative complications compared to planned esophagectomy after neoadjuvant chemoradiotherapy (CRT). We hypothesize that severe postoperative complications may affect not only surgical mortality but also tumor recurrence and long-term survival for patients with salvage esophagectomy after definitive CRT.

Methods

For the present study we reviewed the surgical procedures, postoperative complications, and the prognosis of 65 consecutive patients with thoracic ESCC who underwent the esophagectomy after neoadjuvant (neoadjuvant group: n = 40) or definitive (salvage group: n = 25) CRT.

Results

Most patients underwent right-transthoracic extended esophagectomy and reconstruction using gastric conduit by way of subcutaneous route with left cervical anastomosis. The incidence of postoperative pneumonia was found to be higher in the salvage group than in the neoadjuvant group. In both groups, the survival of patients with R0 resection was significantly better than those with R1/R2 resection. Moreover, in the salvage group, the postoperative survival rate of patients with pneumonia or bacteremia/sepsis was significantly lower than that for patients who did not suffer the same complications. In the neoadjuvant group, R0 resection was selected to be the only independent prognostic factor in univariate and multivariate analysis. In contrast, in the salvage group, R0 resection and bacteremia/sepsis remained significant and were independent of the other factors in multivariate analysis.

Conclusions

This study reveals that postoperative morbidity affects not only the perioperative mortality but also the long-term survival of patients with ESCC who undergo salvage esophagectomy after definitive CRT.     

Risk Group Stratification Based on Preoperative Factors to Predict Survival after Nephroureterectomy in Patients with Upper Urinary Tract Urothelial Carcinoma

Background

After radical nephroureterectomy (RNU), substantial numbers of patients with upper urinary tract urothelial carcinoma (UUT-UC) are ineligible for adjuvant chemotherapy owing to diminished renal function. Accurate preoperative prediction of survival is considered important because neoadjuvant chemotherapy may be as effective for high-risk UUT-UC as for muscle-invasive bladder cancer. We performed risk group stratification to predict survival based on specific preoperative factors.

Methods

We enrolled 536 UUT-UC patients treated with RNU in this retrospective cohort study and assessed preoperative clinical and laboratory variables influencing disease-specific survival.

Results

The median follow-up was 40.9 months. Using univariate analysis, tumor location; number of tumors; hydronephrosis; clinical T stage; clinical N category; voided urine cytology; neoadjuvant chemotherapy; hemoglobin; white blood cell (WBC) counts; and C-reactive protein had a significant influence on disease-specific survival (P < 0.05). Multivariate analysis revealed that clinical T stage, voided urine cytology, and WBC were independent predictors (P = 0.041, P = 0.020, and P = 0.017, respectively). We divided patients into three risk groups based on the number of the three independent predictors: 0, low risk; 1, intermediate risk; 2 and 3, high risk. Significant differences in disease-specific survival were found among these risk groups (P ≤ 0.0047).

Conclusions

Our results suggest that risk group stratification based on preoperative clinical T stage, voided urine cytology, and WBC counts may be useful for selection of UUT-UC patients for neoadjuvant chemotherapy. Prospective studies with larger numbers of patients and a longer follow-up period are needed to confirm our results.     

Preoperative Chemotherapy with Cisplatin and Docetaxel Followed by Surgery and Clip-Oriented Postoperative Chemoradiation in Patients with Localized Gastric or Gastroesophageal Junction Adenocarcinoma: Results from a Phase II Feasibility Study

Background

We conducted a phase II feasibility study using preoperative chemotherapy with cisplatin and docetaxel followed by surgical resection and postoperative chemoradiation in patients with gastric or gastroesophageal cancer.

Methods

Preoperative chemotherapy (two or three cycles) consisted of 50 mg/m² docetaxel and 50 mg/m² cisplatin. Surgical resection was planned 4 weeks after the last chemotherapy cycle. Patients underwent postsurgical chemoradiation, receiving a total dose of 39.6 Gy and 5-fluorouracil (5-FU) continuous infusion (350 mg/m²/day). The primary end-points were feasibility, overall response rate and R0 resectability rate after preoperative chemotherapy. The secondary end-points were tolerability, treatment-associated complications, disease-free survival and overall survival.

Results

Between 2002 and 2004, 15 patients were enrolled in this study. After neoadjuvant treatment, two patients (13%) experienced progressive disease, four patients (27%) showed partial remission and nine patients (60%) showed stable disease. In 11 patients (73%) R0 resectability could be achieved. Six of these patients (54%) were able to undergo postoperative chemoradiation. Notably, five (83%) of these patients were disease free and alive at median follow-up of 72 months. Chemotherapy-associated neutropaenia and neutropaenic fever, anastomotic dehiscence, pulmonary embolism and acute pancreatitis were observed.

Conclusions

The combination of preoperative chemotherapy and postoperative chemoradiation is feasible in a significant subset of gastric cancer patients.     

Neoadjuvant chemotherapy for adult soft tissue sarcoma: comparaison of systemic and intra-arterial chemotherapy

Background

The introduction of a combined-modality approach, which added chemotherapy to local therapy (surgery and radiotherapy), has been controversial. We present our experience of the efficacy of neoadjuvant chemotherapy in patients with high-risk sarcomas and evaluate the benefit of intra-arterial (IA) chemotherapy.

Patients and methods

Forty patients with intermediate to high-grade soft tissue sarcomas (STS) were treated with neoadjuvant chemotherapy from 1994 to 2001 at the Institut Curie. Thirty-seven patients had localized tumours. Neoadjuvant intravenous (IV) chemotherapy consisted of 4–6 cycles of treatment (mainly CYVADIC, MAID). Sixteen patients (40%) received 2 cycles of IA chemotherapy with a combination of adriamycin and cisplatin. Radiotherapy was delivered in an adjuvant setting.

Results

All patients underwent limb-sparing surgical resection after neoadjuvant therapy and pathologic assessment of tumour necrosis was performed on the resected specimens. Two groups of tumours were analysed: 1–95% (28 cases), and 95–100% (10 cases) of pathological necrosis, with a survival benefit in the group with more than 95% necrosis (p = 0.07). IA chemotherapy was superior to IV chemotherapy in terms of the necrosis rate (p = 0.045). With a median follow-up of 51 months, the 2-year overall survival rate was 90% for localized tumours.

Conclusion

Neoadjuvant chemotherapy can be considered to be effective in the treatment of STS. This study demonstrates the benefit of neoadjuvant therapy for patients with a high necrosis rate (very clear tendency) and the contribution of IA chemotherapy to the response rate, but with no survival advantage.     

Resection of Pulmonary Metastases from Colon and Rectal Cancer: Factors to Predict Survival Differ Regarding to the Origin of the Primary Tumor

Background

The purpose of the present study was to determine differences in prognostic factors for survival of patients with pulmonary metastases resected in curative intent from colon or rectum cancer.

Methods

Between 1980 and 2006, prognostic factors after resection of pulmonary metastases in 171 patients with primary rectum or colon tumor were evaluated. Survival of patients after surgical metastasectomy was compared with that of patients receiving standard chemotherapy by matched-pair analysis.

Results

Median survival after pulmonary resection was 35.2 months (confidence interval 27.3–43.2). One-, 3-, and 5-year survival for patients following R0 resection was 88.8, 52.1, and 32.9 % respectively. Complete metastasectomy (R0), UICC stage of the primary tumor, pleural infiltration, and hilar or mediastinal lymph node metastases are independent prognostic factors for survival. Matched-pair analysis confirmed that pulmonary metastasectomy significantly improved survival. Although no difference in survival for patients with pulmonary metastases from lower rectal compared to upper rectal or colon cancer was observed, factors to predict survival are different for patients with lower and middle rectal cancer (R0, mediastinal and/or hilar lymph nodes, gender, UICC stage) compared with patients with upper rectal or colon cancer (R0, number of metastases).

Conclusions

Our results indicate that distinct prognostic factors exist for patients with pulmonary metastases from lower rectal compared with upper rectal or colon cancer. This supports the notion that colorectal cancer should not be considered as a single-tumor entity. Metastasectomy, especially after complete resection resulted in a dramatic improvement of survival compared with patients treated with chemotherapy alone.     

Impact of Obesity on Perioperative Complications and Long-term Survival of Patients with Gastric Cancer

Background

The prevalence of obesity is increasing in the United States. Obesity has been associated with worse surgical outcomes, but its impact on long-term outcomes in gastric cancer is unclear. The aim of this study was to evaluate the effects of being overweight on surgical and long-term outcomes for patients with gastric cancer.

Methods

Patients who underwent curative intent resection for gastric carcinoma from 1985 to 2007 were identified from a prospectively collected gastric cancer database. Overweight was defined as a body mass index (BMI) of 25 kg/m² or higher. Clinical outcomes of overweight and nonoverweight patients were compared.

Results

From the total population of 1,853 patients, 1,125 (60.7 %) were overweight. Overweight patients tended to have more proximal tumors and a lower T stage. Accurate complication data were available on a subset of patients from 2000 to 2007. A BMI of ≥25 was associated with increased postoperative complications (47.9 vs. 35.8 %, p < 0.001). This was mainly due to an increase in the rate of wound infections (8.9 vs. 4.7 %, p = 0.02) and anastomotic leaks (11.8 vs. 5.4 %, p = 0.002). Multivariate logistic regression analysis showed that higher BMI, total gastrectomy, and use of neoadjuvant chemotherapy were associated with increased wound infection and anastomotic leak. Overweight patients were less likely to have adequate lymph node staging (73.3 vs. 79.2 %, p = 0.047). There was no difference in overall survival or disease-specific survival between the two groups.

Conclusions

Increased BMI is a predictor of increased postoperative complications, including anastomotic leak, but it is not a predictor of survival in gastric cancer.     

Neoadjuvant Chemotherapy with Bevacizumab May Improve Outcome after Cytoreduction and Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) for Colorectal Carcinomatosis

Background

In selected patients with colorectal peritoneal carcinomatosis (PC), cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) may improve survival. We aimed to assess whether neoadjuvant chemotherapy with or without bevacizumab is indicated in this patient population.

Methods

Colorectal PC patients were treated with CRS and HIPEC using oxaliplatin (200–460 mg/m²) or mitomycin C (35 mg/m²). Postoperative outcome and long-term survival were prospectively recorded. The impact of clinical variables on overall survival (OS) was assessed using univariate and Cox multivariate analysis.

Results

Between October 2002 and May 2012, 166 patients were treated with CRS and HIPEC. Neoadjuvant chemotherapy alone was administered to 21 % and neoadjuvant chemotherapy with bevacizumab to 16 % of patients. Postoperative mortality and major morbidity were 2.4 and 35 %, respectively. Half of the patients received adjuvant chemotherapy. After a median follow-up of 18 months, OS was 27 months (95 % confidence interval 20.8–33.2). On univariate analysis, OS was associated with extent of disease (P < 0.001), neoadjuvant chemotherapy with bevacizumab (P = 0.021), completeness of cytoreduction (CC) (P < 0.001), and adjuvant chemotherapy (P = 0.04), but not with primary disease site, synchronous presentation, or chemoperfusion drug. In multivariate Cox regression, independent predictors of OS were CC (hazard ratio 0.29, P < 0.001) and neoadjuvant therapy containing bevacizumab (hazard ratio 0.31, P = 0.019).

Conclusions

Long-term OS after CRS and HIPEC for colorectal cancer is associated with CC and neoadjuvant therapy containing bevacizumab. This regimen merits prospective study in patients with resectable PC of colorectal origin.     

The Impact of Neoadjuvant Chemoradiotherapy on Perioperative Outcomes, Tumor Pathology, and Survival in Clinical Stage II and III Esophageal Cancer

Background

The purpose of this study was to evaluate the impact of neoadjuvant chemoradiotherapy (NCR) on perioperative outcomes, tumor pathology, and survival following surgical resection of clinical stage II and III esophageal cancer.

Methods

Patients undergoing esophagectomy for clinical stage II and III cancer were divided into two groups: those who received NCR and those who underwent primary surgery (1991–2011).

Results

A total of 173 (50.9 %) of 340 stage II/III patients received NCR, 108 (31.8 %) patients underwent primary surgery, and 59 (17.4 %) underwent neoadjuvant chemotherapy followed by surgery. Patients who received NCR were younger but had a similar Charlson comorbidity index and incidence of adenocarcinoma. There were no differences between groups in the incidence of complications, in-hospital mortality, and ICU stay, but patients who received NCR demonstrated a reduced length of hospital stay. NCR was associated with a reduced the incidence of positive pathological lymph node status and positive resection margin (3.1 vs. 21.1 %) in stage III esophageal cancer. No overall survival benefit was seen with use of NCR, although a nonsignificant improvement in survival of 22 months (p = 0.06) was noted in patients with adenocarcinoma. Negative resection margin was associated with an improved survival in both stage II and III patients.

Conclusions

This study highlights the importance of planning operations to optimize the opportunity to provide negative surgical resection margins and to identify patients not responding to NCR to allow them to proceed directly to surgery. Additional assessment of the effect of NCR on patients with adenocarcinoma is warranted.