A Systematic Review of Resectability and Survival After Concurrent Chemoradiation in Primarily Unresectable Pancreatic Cancer

Purpose

The objective of this study was to determine the effect on resection rate and survival of neoadjuvant chemoradiotherapy for primarily unresectable locally advanced pancreatic carcinoma.

Methods

A systematic review of recently published literature was performed. Resection rates and survival data were derived from reports published from 2000 onwards. Only recent studies, based on radiotherapy with standard dose and fractionation, have been analyzed.

Results

Thirteen studies with a total of 510 patients met selection criteria. A resection rate of 8.3–64.2% was reported (median, 26.5%). Of the operated patients, 57.1–100% (median, 87.5%) had R0 tumor resection. Most papers reported occasional pathological complete responses (CR, 3.0–8.8%). When outcome in all patients was considered, median survival ranged from 9 to 23 (median, 13.3) months, comparing favorably with literature data based on concurrent chemoradiation alone (range, 8.6–13 months). Surprisingly, in patients with unresectable tumor at presentation, median survival after surgery ranged from 16.4 to 32.3 (median, 23.6) months.

Conclusions

The finding of a high proportion of R0 resection among all resections performed confirms the activity of neoadjuvant radiochemotherapy and should not be neglected. Based on these data, patients with unresectable pancreatic cancer without disease progression after chemoradiotherapy should be considered for radical surgery.     

Restaging Patients with Rectal Cancer Following Neoadjuvant Chemoradiation: A Systematic Review

Background

In the USA, most patients with clinical stage II/III rectal cancer receive neoadjuvant chemoradiation (chemo/XRT) over 5–6 weeks followed by a 6–10-week break before proctectomy. As chemotherapy is delivered at radio-sensitizing doses, there is essentially a 3-month window during which potential systemic disease is untreated. Evidence regarding the utility of restaging patients prior to proctectomy is limited.

Methods

PubMed, Scopus, Web of Science, and the Cochrane Library were searched for studies evaluating the utility of restaging patients with rectal cancer after completion of long-course chemo/XRT, and reporting associated changes in management. Studies that were non-English, included <50 patients, or examining the diagnostic accuracy of imaging modalities were excluded. Study quality was evaluated using the modified Newcastle Ottawa Scale.

Results

Eight studies were identified including a total of 1251 patients restaged between completion of chemo/XRT and proctectomy. All studies were retrospective. Restaging identified new metastatic disease in 72 (6.0%) patients, with 4 studies reporting specific sites: liver (n = 28), lung (n = 8), adrenal (n = 1), bone (n = 1), and multiple sites (n = 7). Overall progression (distant or local) was detected in 88 (7.0%) patients and resulted in a change in management in 77 (87.5%) of these patients. Tumor-related prognostic characteristics were inconsistently reported among studies, precluding meta-analysis.

Conclusions

Although restaging between completion of neoadjuvant chemo/XRT and proctectomy detects disease progression in only a small percentage of patients, findings alter the treatment plan in the vast majority of these patients. Multi-institutional collaboration with analysis of well-defined prognostic variables may better identify patients most likely to benefit from restaging.

     

Survival Impact of Total Resected Lymph Nodes in Esophageal Cancer Patients With and Without Neoadjuvant Chemoradiation

Background

Current esophageal treatment guidelines suggest that, when more than 15 lymph nodes are detected, dissection should be done as the minimum requirement for staging in esophageal squamous cell carcinoma (ESCC) patients undergoing esophagectomy without induction chemoradiotherapy (CRT). However, for neoadjuvant CRT, there is limited information. We sought to clarify the role of lymphadenectomy in ESCC patients with and without neoadjuvant CRT.

Patients and Methods

Data on 3156 ESCC patients receiving esophagectomy with (group 1, n?=?1399) and without (group 2, n?=?1757) neoadjuvant CRT between 2008 and 2014 were collected from a national cancer registry in Taiwan. The impact of the resected lymph nodes on overall survival was assessed according to pathologic stages. A Cox regression model was used to identify prognostic factors for overall survival.

Results

Five-year overall survival rates were 35.6% for the entire group, 30.32% for group 1, and 39.55% for group 2 (p?<?0.0001 for group 1 vs group 2). The best cutoff value was 21 lymph nodes in both group 1 and group 2. In group 1, the independent prognostic factors included age?≥?54 years, clinical N status, y-pathologic T, y-pathologic N, y-pathologic stage, grade, location, margin status, esophagectomy (thoracoscopic vs open), and number of total resected lymph nodes (≤?21 vs?>?21). For group 2, the independent prognostic factors were gender, clinical stage, pathologic T, pathologic N, tumor length, grade, and margin status.

Conclusions

Extent of lymphadenectomy was associated with survival in patients with neoadjuvant CRT followed by esophagectomy. The optimum lymphadenectomy should be modulated by pathologic stage.

     

Systematic Review of FDG-PET Prediction of Complete Pathological Response and Survival in Rectal Cancer

Background

Advances in the management of rectal cancer have resulted in an increased application of multimodal therapy with the aim of tailoring therapy to individual patients. Complete pathological response (pCR) is associated with improved survival and may be potentially managed without radical surgical resection. Over the last decade, there has been increasing interest in the ability of functional imaging to predict complete response to treatment. The aim of this review was to assess the role of ¹⁸F-flurordeoxyglucose positron emission tomography (FDG-PET) in prediction of pCR and prognosis in resectable locally advanced rectal cancer.

Methods

A search of the MEDLINE and Embase databases was conducted, and a systematic review of the literature investigating positron emission tomography (PET) in the prediction of pCR and survival in rectal cancer was performed.

Results

Seventeen series assessing PET prediction of pCR were included in the review. Seven series assessed postchemoradiation SUVmax, which was significantly different between response groups in all six studies that assessed this. Nine series assessed the response index (RI) for SUVmax, which was significantly different between response groups in seven series. Thirteen studies investigated PET response for prediction of survival. Metabolic complete response assessed by SUV2max or visual response and RISUVmax showed strong associations with disease-free survival (DFS) and overall survival (OS).

Conclusion

SUV2max and RISUVmax appear to be useful FDG-PET markers for prediction of pCR and these parameters also show strong associations with DFS and OS. FDG-PET may have a role in outcome prediction in patients with advanced rectal cancer.     

Influence of Neoadjuvant Chemoradiation on the Number and Size of Analyzed Lymph Nodes in Esophageal Cancer

Background  

Studies have shown that along with primary tumor response, lymph node status after RTx/CTx is one of the most important prognostic factors for advanced esophageal carcinoma. The goal of our study was to investigate the influence of neoadjuvant radiochemotherapy (RTx/CTx) on lymph nodes (LN).     

A Systematic Review and Meta-analysis of Survival and Surgical Outcomes Following Neoadjuvant Chemoradiotherapy for Pancreatic Cancer

Introduction  

This systematic review and meta-analysis aims to characterize the surgically important benefits and complications associated with the use of neoadjuvant chemoradiotherapy for the treatment of both resectable and initially unresectable pancreatic cancer. Studies were identified through a systematic literature search and analyzed by two independent reviewers. Survival, peri-operative complications, death rate, pancreatic fistula rate, and the incidence of involved surgical margins were analyzed and subject to meta-analysis.     

Impact of Solitary Involved Lymph Node on Outcome in Localized Cancer of the Esophagus and Esophagogastric Junction

Node-positive esophageal cancer is associated with a dismal prognosis. The impact of a solitary involved node, however, is unclear, and this study examined the implications of a solitary node compared with greater nodal involvement and node-negative disease. The clinical and pathologic details of 604 patients were entered prospectively into a database from1993 and 2005. Four pathologic groups were analyzed: node-negative, one lymph node positive, two or three lymph nodes positive, and greater than three lymph nodes positive. Three hundred and fifteen patients (52%) were node-positive and 289 were node-negative. The median survival was 26 months in the node-negative group. Patients (n = 84) who had one node positive had a median survival of 16 months (p = 0.03 vs node-negative). Eighty-four patients who had two or three nodes positive had a median survival of 11 months compared with a median survival of 8 months in the 146 patients who had greater than three nodes positive (p = 0.01). The survival of patients with one node positive [number of nodes (N) = 1] was also significantly greater than the survival of patients with 2–3 nodes positive (N = 2–3) (p = 0.049) and greater than three nodes positive (p < 0001). The presence of a solitary involved lymph node has a negative impact on survival compared with node-negative disease, but it is associated with significantly improved overall survival compared with all other nodal groups.     

Improved Long-Term Survival After Esophagectomy for Esophageal Cancer: Influence of Epidemiologic Shift and Neoadjuvant Therapy

Background

The study was done to determine long-term outcomes of surgically treated esophageal cancer and to identify trends in epidemiology, oncological therapy, and oncological prognosis over the last two decades.

Methods

Overall survival in 304 patients undergoing esophagectomy was analyzed. Fifty-three percent had squamous cell carcinoma and 46 % had adenocarcinoma (AC). A total of 161 patients received neoadjuvant chemoradiation, 38 received neoadjuvant chemotherapy, and 105 were treated with surgery alone.

Results

Median survival (MS) increased significantly from 18.0 months (1988–1994) to 26.6 months (1995–2001) and to 59.3 months (2002–2011; p?<?0.001). The proportion of AC (22 vs 35 vs 65 %; p?<?0.001) and the proportion of patients treated with neoadjuvant therapy (neoT; 15.9 vs 85.3 vs 77.8 %; p?<?0.001) increased during the treatment period. After neoT, a beneficial outcome with a MS of 45.6 vs. 20.4 months (p?=?0.003) was found. Lymph node ratio [LNR; relative risk (RR), 5.4; p?<?0.001], response to neoT (RR, 1.6; p?<?0.004), and histological subtype (RR, 1.7; p?<?0.003) were identified as independent parameters of survival.

Conclusion

Since 1988, the outcome of surgically resected esophageal cancer strongly improved. Besides tumorbiological factors like histological type and LNR, the outcome is also affected by the increasing use of neoT towards favorable survival rates.     

Clinical and Pathologic Evaluation of the Effectiveness of Neoadjuvant Chemoradiation Therapy in Advanced Esophageal Cancer Patients

Background  Chemoradiation therapy (CRT) has the strongest antitumor effect against local tumors of esophageal cancer; however, no standard strategy has yet been established to achieve a clinical complete response (CR) after CRT. The aim of this study was to clarify when a decision can be made to perform further treatment for a clinical CR. Methods  We evaluated 78 patients that underwent an esophagectomy after neoadjuvant CRT in our department between 1998 and 2007. The study investigated the clinical and pathologic results of neoadjuvant CRT. Results  Of the 78 cases, 19 (24.3%) were a pathologic CR (Grade 3). Pathologic CR could be estimated in only 3 of 8 clinical CR cases (37.5%). On the other hand, 12 (20.7%) of the 58 clinical partial response (PR) cases achieved pathologic CR. Likewise, 4 cases (36.4%) achieved pathologic CR among the clinical no change/progressive disease (NC/PD) patients. Conclusions  The clinical evaluation for CRT does not reflect the pathologic effectiveness and, even if clinical CR was achieved, viable cancer cells were still present at the primary site in the majority of the population.     

Neoadjuvant Chemoradiotherapy for Esophageal Cancer: A Review of Meta-Analyses

Background  

Most randomized controlled trials (RCTs) that have compared neoadjuvant chemoradiation followed by surgery with surgery alone for locally advanced esophageal cancer have shown no difference in survival between the two treatments. Meta-analyses on neoadjuvant chemoradiation in esophageal cancer, however, are discordant.     

Survival After Neoadjuvant Therapy Compared with Surgery Alone for Resectable Esophageal Cancer in a Population-based Study

Background Esophagectomy remains the standard treatment for resectable esophageal cancer, but the cure rate is low. Neoadjuvant therapy has been tried in attempts to prolong survival and reduce tumor recurrence. The aim of this study was to assess the surgical outcomes with and without neoadjuvant treatment for resectable esophageal cancer in a population-based setting. Methods All 1,155 patients treated with esophagectomy for esophageal cancer in Sweden in 1987 through 2000 with or without neoadjuvant therapy were identified and followed up in nationwide registers up to 18 October 2004. Tumor characteristics and response to neoadjuvant treatment were obtained from histopathological reports. Hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for potential confounding factors were calculated by a Cox proportional hazards regression model. Results Overall survival was similar in the groups with and without neoadjuvant therapy (adjusted HR 0.99, 95% CI 0.86–1.16). The 3-year survival rates were 34.6% and 32.0%, respectively. Survival was better among the 27.6% of the neoadjuvant group with a complete histopathological response (HR 0.71, 95% CI 0.53–0.94) compared with the surgery only group. Patients without complete response to neoadjuvant therapy had seemingly poorer survival (HR 1.10, 95% CI 0.94–1.29). Conclusions Surgical outcomes with and without neoadjuvant therapy were equivalent. Only patients with a complete histopathological response after neoadjuvant treatment had better survival.     

FDG-PET Parameters as Prognostic Factor in Esophageal Cancer Patients: A Review

Background  

¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) has been used extensively to explore whether FDG Uptake can be used to provide prognostic information for esophageal cancer patients. The aim of the present review is to evaluate the literature available to date concerning the potential prognostic value of FDG uptake in esophageal cancer patients, in terms of absolute pretreatment values and of decrease in FDG uptake during or after neoadjuvant therapy.     

ASO Author Reflections: Revisiting the Role of Induction Chemotherapy Plus Neoadjuvant Chemoradiation for Esophageal and Gastroesophageal Junction Adenocarcinoma

Annals of Surgical Oncology -     

Reduced Incidence of Nodal Micrometastasis after Major Response to Neoadjuvant Chemoradiation in Locally Advanced Esophageal Cancer

Background

Neoadjuvant treatment modalities for esophageal cancer were developed to improve local tumor control as well as to reduce lymph node metastases and distant metastases in patients with locally advanced esophageal cancer. The influence on nodal micrometastasis has not yet been evaluated.

Methods

This study includes 52 patients with localized (cT2-4, Nx, M0) esophageal cancers (21 adenocarcinomas, 31 squamous cell cancers) who received neoadjuvant chemoradiation (36Gy, 5-FU, cisplatin) followed by transthoracic en bloc esophagectomy with two field lymphadenectomy. The extent of histomorphologic regression was categorized into major (< 10%) and minor response (>10% vital residual tumor cells) as recently reported. A total of 1186 lymph nodes were diagnosed as negative for metastases by routine histopathological analysis and were further examined for the presence of isolated tumor cells with the monoclonal anti-epithelial antibody AE1/AE3.

Results

Twenty-two tumors (42.3%) showed a major histopathologic response whereas in 30 tumors (57.7%) only a minor response was present. Of 32 patients with a pN0 category, major response was present in 19 (59.4%) tumors, whereas 13 (40.6%) tumors showed minor response. Nine (69%) out of 13 patients with minor response had AE1/AE3-positive cells in their lymph nodes, whereas only four (21%) out of 19 pN0-patients with major response showed nodal micrometastasis (P = 0.013, χ²-test).

Conclusions

If tumors show a major histomorphologic response following neoadjuvant chemoradiation, the presence of nodal micrometastasis is significantly reduced compared to those with minor response.     

Recurrence Rates and Prognostic Factors in ypN0 Rectal Cancer After Neoadjuvant Chemoradiation and Total Mesorectal Excision

Background  

Neoadjuvant chemoradiation followed by surgery and adjuvant chemotherapy is typically recommended for patients with locally advanced rectal cancer. Patients with pathologically node-negative tumors have an improved prognosis, but recurrence patterns and independent prognostic factors in these patients have been incompletely characterized.