Maintained survival outcome after reducing lymphadenectomy rates and optimizing adjuvant treatment in endometrial cancer.

OBJECTIVE: Main controversies in endometrial cancer treatment include the role of lymphadenectomy and optimal adjuvant treatment. We assessed clinical outcome in a population-based endometrial cancer cohort in relation to changes in treatment management over two decades. METHODS: All consenting endometrial cancer patients receiving primary treatment at Haukeland University Hospital from 2001 to 2019 were included (n = 1308). Clinicopathological variables were evaluated for year-to-year changes. Clinical outcome before and after discontinuing adjuvant radiotherapy and individualizing extent of lymphadenectomy was analyzed. RESULTS: The rate of lymphadenectomy was reduced from 78% in 2001-2012 to 53% in 2013-2019. The rate of patients with verified lymph node metastases was maintained (9% vs 8%, p = 0.58) and FIGO stage I patients who did not undergo lymphadenectomy had stable 3-year recurrence-free survival (88% vs 90%, p = 0.67). Adjuvant chemotherapy for completely resected FIGO stage III patients increased from 27% to 97% from 2001 to 2009 to 2010-2019, while adjuvant radiotherapy declined from 57% to 0% (p < 0.001). These patients had improved 5-year overall- and recurrence-free survival; 0.49 [95% CI: 0.37-0.65] in 2001-2009 compared to 0.61 [0.45-0.83] in 2010-2019, p = 0.04 and 0.51 [0.39-0.68] to 0.71 [0.60-0.85], p = 0.03, respectively. For stage I, II and IV, survival rates were unchanged. CONCLUSIONS: Our study demonstrates that preoperative stratification by imaging and histological assessments permits a reduction in lymphadenectomy to around 50%, and is achievable without an increase in recurrences at 3 years. In addition, our findings support that adjuvant chemotherapy alone performs equally to adjuvant radiotherapy with regard to survival, and is likely superior in advanced stage patients.

Evaluating the Impact of ESPAC-1 on Shifting the Paradigm of Pancreatic Cancer Treatment.

BACKGROUND: In 2004, the European Study Group for Pancreatic Cancer (ESPAC)-1 long-term data concluded that adjuvant chemotherapy provided a survival benefit for patients with pancreatic ductal adenocarcinoma (PDAC), whereas adjuvant chemoradiation was associated with worse overall survival. In this study, we investigated how long it took for US practice patterns to change following this trial. METHODS: The National Cancer Database was used to identify patients with stage I-III PDAC who underwent R0 or R1 resection followed by adjuvant chemotherapy or chemoradiation between 1998 and 2015. A multivariate analysis was performed to determine predictors of receiving adjuvant chemoradiation in the post-ESPAC-1 era. RESULTS: Between 1998 and 2015, adjuvant chemotherapy use increased from 2.9% to 51.6%, whereas adjuvant chemoradiation decreased from 49.5% to 22.9%. In 2010, adjuvant chemotherapy utilization surpassed that of chemoradiation. For patients diagnosed in the post-ESPAC-1 era, adjuvant chemotherapy (n = 7733) and chemoradiation (n = 6969) groups were compared. Patients who underwent adjuvant chemoradiation were younger, had private insurance, underwent surgery at nonacademic centers, and had more pathologically advanced cancers (all P < 0.01). After 2010, R1 resection was the strongest independent predictor of adjuvant chemoradiation use by multivariate analysis (OR 2.05, CI 1.8-2.3, P < 0.01). CONCLUSIONS: Adjuvant chemotherapy use exceeded that of adjuvant chemoradiation 6 y after the final publication of ESPAC-1 in 2004, highlighting the challenges of disseminating and adopting clinical data. After 2010, R1 disease was the most significant predictor of receiving adjuvant chemoradiation. Prospective studies are underway to definitively address the role of adjuvant chemoradiation in PDAC.

Populational trends and outcomes of postoperative radiotherapy for high-risk early-stage cervical cancer with lymph node metastasis: concurrent chemo-radiotherapy versus radiotherapy alone.

BACKGROUND: Pelvic lymph node metastasis carries the highest impact on decreased survival among surgical-pathological risk factors for early-stage cervical cancer. Although concurrent administration of chemotherapy during postoperative radiotherapy is the current standard treatment for surgically treated high-risk early-stage cervical cancer, its effectiveness specific to node-positive disease has not been completely studied. OBJECTIVE: To examine the association between the use of concurrent chemotherapy and survival in women with early-stage cervical cancer and nodal metastasis receiving adjuvant radiotherapy. MATERIALS AND METHODS: This is a population-based cohort study using the Surveillance, Epidemiology, and End Results Program from 1988 to 2016. Women with stage T1-2 cervical cancer with pelvic lymph node metastasis who underwent hysterectomy and received postoperative radiotherapy were examined. Trends, characteristics, and overall survival were compared between women who received postoperative radiotherapy alone (n = 729) or in combination with concurrent chemo-radiotherapy (n = 1809). Propensity score-based inverse probability of treatment weighting was used to account for the effect of measured covariates on treatment selection. RESULTS: Among 2538 women, there was a marked increase in the use of concurrent chemotherapy from 1997 to 2000 (20.7% to 78.5%, P = .052), followed by a more gradual rise through 2016 (88.3%, P < .001). In a multivariable model, women with non-squamous cell carcinomas and those diagnosed more recently were more likely to receive concurrent chemo-radiotherapy, whereas older women were less likely to receive concurrent chemo-radiotherapy (all, P < .05). At the population level, the 5-year overall survival rates remained unchanged (annual percent change for 1997-2012: -0.1; 95% confidence interval, -1.2 to 1.0; P = .776). In a propensity score weighted cohort, women who received concurrent chemo-radiotherapy had a 5-year overall survival rate similar to women treated with radiotherapy alone (73.1% vs 73.6%; hazard ratio, 1.004; 95% confidence interval, 0.887-1.136; P = .955). Significant differences were also not seen in older women, nonsquamous types, stage T2 disease, and multiple node metastases (all, P > .05). CONCLUSION: Despite the marked increase in the use of concurrent chemo-radiotherapy for women with early-stage cervical cancer and nodal metastases, there was no association between use of concurrent chemotherapy during postoperative radiotherapy and improved survival.

Management of Patients With Adenocarcinoma or Squamous Cancer of the Esophagus.

Esophageal cancer is characterized by early and frequent metastasis. Surgery is the primary treatment for early-stage disease, whereas patients with patients with locally advanced disease receive perioperative chemotherapy or chemoradiotherapy. Squamous cancers can be treated with primary chemoradiotherapy without surgery, depending on their response to therapy and patient tolerance for subsequent surgery. Chemotherapy with a fluorinated pyrimidine and a platinum agent, followed by later treatment with taxanes and irinotecan, provides some benefit. Agents that inhibit the erb-b2 receptor tyrosine kinase 2 (ERBB2 or HER2), or vascular endothelial growth factor, including trastuzumab, ramucirumab, and apatinib, increase response and survival times. Esophageal adenocarcinomas have mutations in tumor protein p53 and mutations that activate receptor-associated tyrosine kinase, vascular endothelial growth factor, and cell cycle pathways, whereas esophageal squamous tumors have a distinct set of mutations. Esophageal cancers develop systems to evade anti-tumor immune responses, but studies are needed to determine how immune checkpoint modification contributes to esophageal tumor development.

National guidelines may reduce socioeconomic disparities in treatment selection for esophageal cancer.

The 2011 National Comprehensive Cancer Network guidelines first incorporated the results of the landmark CROSS trial, establishing induction therapy (chemotherapy ± radiation) and surgery as the treatment standard for locoregional esophageal cancer in the United States. The effect of guideline publication on socioeconomic status (SES) inequalities in cancer treatment selection remains unknown. Patients diagnosed with Stage II/III esophageal cancer between 2004 and 2013 who underwent curative treatment with definitive chemoradiation or multimodality treatment (induction and surgery) were identified from the Surveillance, Epidemiology and End Results (SEER)-Medicare registry. Clinicopathologic characteristics were compared between the two therapies. Multivariable regression analysis was used to adjust for known factors associated with treatment selection. An interaction term with respect to guideline publication and SES was included Of the 2,148 patients included, 1,478 (68.8%) received definitive chemoradiation and 670 (31.2%) induction and surgery. Guideline publication was associated with a 16.1% increase in patients receiving induction and surgery in the low SES group (21.4% preguideline publication vs. 37.5% after). In comparison, a 4.5% increase occurred during the same period in the high SES status group (31.8% vs. 36.3%). After adjusting for factors associated with treatment selection, guideline publication was associated with a 78% increase in likelihood of receiving induction and surgery among lower SES patients (odds ratio 1.78; 95% confidence interval (CI): 1.05,3.03). Following the new guideline publication, patients living in low SES areas were more likely to receive optimal treatment. Increased dissemination of guidelines may lead to increased adherence to evidence-based treatment standards.

Progress in the Treatment and Outcomes for Early-Stage Non-Small Cell Lung Cancer.

PURPOSE: The purpose of this study is to assess temporal trends in population-based treatment and survival rates in patients with early-stage non-small cell lung cancer (NSCLC). METHODS: Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Chi-square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 23.0. RESULTS: Fifty-seven thousand and eighty-eight NSCLC patients with early-stage disease from 1988 to 2014 were identified. 6409 (11.2%) were diagnosed in 1988-1994, 5800 (10.2%) 1995-1999, 13,031 (22.8%) 2000-2004, 15,786 (27.7%) 2005-2009, and 16,062 (28.1%) 2010-2014. We observed a significant increase in the proportion of older patients, adenocarcinoma histology, and rate of wedge resection over the study period. The five-year overall survival (OS) for the entire cohort was 63.3%. Those undergoing resection without adjuvant therapy had the highest outcomes. Lobectomy was associated with better outcomes compared to wedge resection or pneumonectomy. A significant difference in five-year OS by year of diagnosis (1988-1994: 58.8% vs. 1995-1999: 60.6% vs. 2000-2004: 63.2% vs. 2005-2009: 66.1%; p < 0.001) was observed. This significant OS difference was also observed regardless of age, surgery type, and T stage, but also only in those with adenocarcinoma. On multivariable analysis, year of diagnosis, age, gender, race, treatment and surgery type, histology, T stage, and tumor grade remained independent prognostic factors for OS. CONCLUSIONS: Overall survival for early-stage NSCLC has significantly improved over the recent decades despite an increasing proportion of older patients and those undergoing sublobar resection or SBRT. This finding may be limited to those with adenocarcinoma.

Changes in treatment patterns for patients with locally advanced rectal cancer in the United States over the past decade: An analysis from the National Cancer Data Base.

BACKGROUND: In the United States, neoadjuvant chemoradiotherapy (NACRT) is widely accepted as the standard of care in the treatment of patients with locally advanced rectal cancer. In the current study, the authors attempted to examine patterns of treatment in the United States over the past decade. METHODS: Using the National Cancer Data Base, a total of 66,197 patients who were diagnosed with American Joint Committee on Cancer stage II to III rectal adenocarcinoma and treated between 2004 and 2012 were identified. The authors described trends in the receipt of treatment for 3 time periods (2004-2006, 2007-2009, and 2010-2012) and analyzed 5-year overall survival probabilities for 28,550 patients treated between 2004 and 2007. RESULTS: Receipt of NACRT increased significantly from 42.9% between 2004 and 2006 to 50.0% between 2007 and 2009, and to 55.0% between 2010 and 2012 (P < .0001). In contrast, the use of adjuvant chemoradiotherapy (CRT) decreased from 16.7% between 2004 and 2006 to 10.5% between 2007 and 2009, and to 6.7% between 2010 and 2012 (P < .0001). Similarly, the use of surgery alone decreased from 13.1% between 2004 and 2006 to 8.7% between 2010 and 2012 (P < .0001). Older age, the presence of comorbidities, larger primary tumor size, lymph node involvement, not being of non-Hispanic white race/ethnicity, lack of private insurance, and treatment at a facility that did not have a high case volume were associated with a significantly lower possibility of receiving NACRT. The 5-year overall survival rates for patients treated with NACRT, surgery and adjuvant CRT, surgery alone, and definitive CRT were 72.4%, 70.9%, 44.9%, and 48.8%, respectively. CONCLUSIONS: The use of NACRT before surgery in US patients with rectal cancer has substantially increased over the past decade. However, only approximately one-half of patients currently receive this standard therapy, which could be explained in part by socioeconomic factors. Trimodality therapy is associated with the best outcomes for these patients. Cancer 2016;122:1996-2003. © 2016 American Cancer Society.

Treatment trends and survival effects of chemotherapy for hypopharyngeal cancer: Analysis of the National Cancer Data Base.

BACKGROUND: The current study was performed to characterize trends and survival outcomes for chemotherapy in the definitive and adjuvant treatment of hypopharyngeal cancer in the United States. METHODS: A total of 16,248 adult patients diagnosed with primary hypopharyngeal cancer without distant metastases between 1998 and 2011 were identified in the National Cancer Data Base. The association between treatment modality and overall survival was analyzed using Kaplan-Meier survival curves and 5-year survival rates. A multivariate Cox regression analysis was performed on a subset of 3357 cases to determine the treatment modalities that predict improved survival when controlling for demographic and clinical factors. RESULTS: There was a significant increase in the use of chemotherapy with radiotherapy both as definitive treatment (P<.001) and as adjuvant chemoradiotherapy with surgery (P=.001). This was accompanied by a decrease in total laryngectomy/pharyngectomy rates (P<.001). Chemoradiotherapy was associated with improved 5-year survival compared with radiotherapy alone in the definitive setting (31.8% vs 25.2%; log rank P<.001). Similarly, in multivariateanalysis, definitive radiotherapy was found to be associated with compromised survival compared with definitive chemoradiotherapy (hazard ratio, 1.51; P<.001). CONCLUSIONS: Survival analysis revealed that overall 5-year survival rates were higher for chemoradiotherapy compared with radiotherapy alone in the definitive setting, but were comparable between surgery with chemoradiotherapy and surgery with radiotherapy. Cancer 2016;122:1853-60. © 2016 American Cancer Society.

Surgical Results and Oncologic Outcomes for Rectal Cancer with Tailored Mesorectal Excision over Two Decades.

OBJECTIVE: This study aimed to compare the characteristics of the tumors, the management strategy, and oncologic outcomes of patients with rectal cancer surgery in these two periods: period 1 (1993-2001) and period 2 (2002-2011). METHODS: All patients who underwent radical resection of rectal cancer from 1993 to 2011 were included. Comparisons of the patients' demographics, characteristics, operating results, and oncologic outcome between the two periods were undertaken. RESULTS: Radical resection for rectal cancer was performed in 1611 patients (993 men). Patients were significantly older and more had comorbid medical diseases in period 2. More laparoscopic resections were performed and more patients had preoperative chemoradiation in period 2. The postoperative mortality was significantly lower and the hospital stay was significantly shorter in period 2. In those with non-metastatic cancer, the 5-year local recurrences of patients in period 1 and period 2 were 11.9 and 5.9 %, respectively. (p = 0.002) The patients in period 2 had significantly better 5-year overall (68.1 vs. 60.2 %, p = 0.003) and 5-year cancer-specific survival (76.1 vs. 69.4 %, p < 0.001) when compared with those treated in period 1. The improvement occurred mainly in patients with abdominoperineal resection and those with stage III diseases. In the multivariate analysis, among the other histological factors, operations performed in period 2 and laparoscopic surgery were independent factors associated with better overall survival. CONCLUSIONS: Significant improvement in the surgical outcomes in terms of a lower recurrence rate and better survival was achieved in the recent years with the increase in neoadjuvant therapy and the application of laparoscopic surgery.

Recent trends and predictors of multimodality treatment for oesophageal, oesophagogastric junction, and gastric cancer: A Dutch cohort-study.

BACKGROUND: In recent years, evidence supporting multimodality treatment for oesophageal, oesophagogastric junction (OGJ), and gastric cancer has accumulated. This population-based cohort-study investigates trends and predictors of utilisation of multimodality treatment for oesophagogastric cancer in the Netherlands. PATIENTS AND METHODS: Data were obtained from the Netherlands Cancer Registry regarding patients with oesophageal (n = 5450), OGJ (n = 2168) and gastric cancer (n = 6683) without distant metastases who had undergone R0 or R1 surgery diagnosed between 2000 and 2012. Follow-up was completed until February 2014. Preoperative/postoperative chemotherapy and/or radiotherapy combined with surgery were considered multimodality treatment. Logistic regression analysis was performed to analyse the association of age, gender, socioeconomic status, clinical T and N classification, hospital type, comprehensive cancer centre network region, and year of diagnosis, with multimodality treatment receipt. Additional analyses were performed to explore differences in trends of utilisation of multimodality treatment between academic and non-academic hospitals. RESULTS: Multimodality treatment utilisation for oesophageal, OGJ and gastric cancer increased significantly to 90%, 85% and 56% in 2012, respectively. In oesophageal and OGJ cancer patients, preoperative chemoradiotherapy was most frequently administered (85% and 47% in 2012, respectively), and in gastric cancer patients preoperative chemotherapy (47% in 2012). Lower age, higher clinical T and N classification, and diagnosis in more recent years were significantly associated with more frequent multimodality treatment receipt. The adoption of most types of multimodality treatment in academic hospitals preceded non-academic hospitals by a year. CONCLUSION: In the Netherlands, the utilisation of multimodality treatment for oesophagogastric cancer has significantly increased during the past decade, especially in oesophageal and OGJ cancer. Multimodality treatment utilisation was especially dependent on patient and tumour characteristics and year of diagnosis, but multimodality treatment trends seem to be related to the publication of landmark studies, participation in nationally running clinical trials, and hospital type, preceding national guidelines.

Time trends, improvements and national auditing of rectal cancer management over an 18-year period.

AIM: The main aims were to explore time trends in the management and outcome of patients with rectal cancer in a national cohort and to evaluate the possible impact of national auditing on overall outcomes. A secondary aim was to provide population-based data for appraisal of external validity in selected patient series. METHOD: Data from the Swedish ColoRectal Cancer Registry with virtually complete national coverage were utilized in this cohort study on 29 925 patients with rectal cancer diagnosed between 1995 and 2012. Of eligible patients, nine were excluded. RESULTS: During the study period, overall, relative and disease-free survival increased. Postoperative mortality after 30 and 90 days decreased to 1.7% and 2.9%. The 5-year local recurrence rate dropped to 5.0%. Resection margins improved, as did peri-operative blood loss despite more multivisceral resections being performed. Fewer patients underwent palliative resection and the proportion of non-operated patients increased. The proportions of temporary and permanent stoma formation increased. Preoperative radiotherapy and chemoradiotherapy became more common as did multidisciplinary team conferences. Variability in rectal cancer management between healthcare regions diminished over time when new aspects of patient care were audited. CONCLUSION: There have been substantial changes over time in the management of patients with rectal cancer, reflected in improved outcome. Much indirect evidence indicates that auditing matters, but without a control group it is not possible to draw firm conclusions regarding the possible impact of a quality control registry on faster shifts in time trends, decreased variability and improvements. Registry data were made available for reference.

Adjuvant therapy for pancreatic cancer.

Survival for patients with pancreas cancer is correlated to stage. Only 20% of patients present with localized disease amenable to potentially curative resection but, despite resection, the 5-year survival rate for early stage patients remains less than 25%. Current accepted standard of care is adjuvant gemcitabine following curative resection but there have been no conclusions regarding the role or timing of adjuvant chemoradiation. Although systemic disease represents the major risk for failure following resection, there are patients who would benefit from adjuvant local therapy that remain difficult to identify at present. This year at 2014 ASCO Gastrointestinal Cancers Symposium, Cho at al. (Abstract #325) presented the results of adjuvant gemcitabine with the addition of docetaxel followed by 5-FU chemoradiation for patients with resected pancreatic cancer. Kumar et al. (Abstract #330) compared adjuvant chemoradiation to adjuvant chemotherapy. Lastly Heestand et al. (Abstract #176) used a novel way to look at different biomarkers in serum of patients in the RTOG 9407 study and evaluated the survival depending on the type of chemotherapy used. A lower serum CEA and CA 19-9 gave a better overall survival in all patients which has already been established. Low levels of matrix metalloproteinase-7 (MMP-7) predicted an overall survival benefit from adjuvant gemcitabine, but not from 5-FU.

New perspectives in treatment decision for integrated management of rectal cancer: multimodal research for multimodal treatments.

Rectal cancer management improved results in the last thirty-five applying new integrated treatment options. Preoperative radiochemotherapy or radiotherapy alone joined to the modern surgery gaining significant improvement of outcomes. Nevertheless, a definitive conclusion about superiority of one on the other in term of survival and toxicity is still lacking, and further improvement is in general required and seems obtainable. The need for a wide sharing of the accumulated knowledge is represented by the consensus conferences that over the years summarizes the state of the art for the management of rectal cancer. One of the most promising opportunities comes from the attempt of characterization of the tumor heterogeneity. An always-increasing number of new parameters come from different sources including genomic, imaging, pathological features and many others. The need of new informatics technologies able to handle and continuously incorporate new inputs derived from the evidences is also imperative. The combined use of large shared databases and "learning models" could allow generating and rapidly testing new hypotheses, providing further survival improvement in the next years.

Patterns of care for locally advanced vulvar cancer.

OBJECTIVE: Patients with locally advanced vulvar carcinoma can be treated with primary surgery or neoadjuvant chemoradiation. Neoadjuvant treatment appears to be associated with decreased morbidity and acceptable long-term outcomes. We examined the patterns of care for women with locally advanced vulvar cancer. STUDY DESIGN: Data from the Surveillance, Epidemiology, and End Results (SEER) database was used to examine women with stage III-IVA vulvar cancer treated from 1988 to 2008. Primary therapy was classified as surgery or radiation. Multivariable logistic regression models were developed to examine the use of primary radiotherapy. RESULTS: We identified a total of 2292 women including 1757 who underwent primary surgery (76.7%) and 535 treated with primary radiation (23.3%). The use of primary radiation increased with time from 18.0% in 1988 to 30.1% in 2008. In a multivariable model, older women (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.03-1.72), black women (OR, 1.59; 95% CI, 1.14-2.23), and patients with stage IVA tumors (OR, 2.23; 95% CI, 1.78-2.81) were more likely to receive primary radiation. Among women treated with primary radiotherapy, only 17.8% ultimately underwent surgical resection. CONCLUSION: The use of primary radiation for locally advanced vulvar cancer is limited but has increased over time. Multiple patient and tumor factors influence use. The majority of patients with stage III-IVA vulvar cancer treated with primary radiation therapy did not undergo surgical resection.

Recommendations from an international consensus conference on the current status and future of neoadjuvant systemic therapy in primary breast cancer.

The use of neoadjuvant systemic therapy (NST) for the treatment of primary breast cancer has constantly increased, especially in trials of new therapeutic regimens. In the 1980 s, NST was shown to substantially improve breast-conserving surgery rates and was first typically used for patients with inoperable locally advanced or inflammatory breast cancer. Investigators have since also used NST as an in vivo test for chemosensitivity by assessing pathologic complete response. Today, by using pathologic response and other biomarkers as intermediate end points, results from trials of new regimens and therapies that use NST are aimed to precede and anticipate the results from larger adjuvant trials. In 2003, a panel of representatives from various breast cancer clinical research groups was first convened in Biedenkopf to formulate recommendations on the use of NST. The obtained consensus was updated in two subsequent meetings in 2004 and 2006. The most recent conference on recommendations on the use of NST took place in 2010 and forms the basis of this report.

Improved local control of rectal cancer reduces distant metastases.

AIM: The purpose of the present national study was to determine whether improved local control has been accompanied by a change in the incidence of metastases. METHOD: The data were from a national population-based rectal cancer registry and included all 6501 rectal cancer patients treated for cure. The study periods were 1993-1997, 1998-2000, 2001-2003 and 2004-2006. RESULTS: Major changes in the handling of rectal cancer from the first to the last study period included an increased use of MRI from zero to 81% and the use of preoperative radiotherapy from 5% to 20%. The proportion of patients with circumferential resection margin (CRM) ≤2mm decreased from 23% to 13%. The 4-year rate of local recurrence decreased from 13% to 8% (P<0.001), the overall survival increased from 65% to 73% (P<0.001) and the incidence of distant metastases decreased from 25% to 19% (P<0.001) from the first to the last period. The risk of metastases decreased by 29% (hazard ratio 0.71, 95% CI 0.60-0.84). CONCLUSION: Improved diagnostics and treatment of rectal cancer aiming at better local control and survival have resulted in a significant reduction in the incidence of distant metastases.

Adjuvant strategies for resectable pancreatic cancer: have we made progress?

Substantial controversy remains regarding the optimal adjuvant treatment for patients with resectable pancreatic adenocarcinoma. Despite improvements in radiation techniques, systemic therapies, and incorporation of targeted agents, the 5-year survival rates for early stage patients remains less than 25% and the optimal adjuvant treatment approach remains unclear. Here we summarize the data presented at the 2012 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium regarding controversial issues surrounding the role, timing, and selection of patients for adjuvant chemoradiation strategies following curative resection for pancreatic adenocarcinoma. (Abstracts #301, #333, and #206).

Locally advanced pancreatic adenocarcinoma: update and progress.

Pancreatic cancer, the 4th leading cause of cancer death in the U.S., remains a challenging disease for the oncology community. Less than 20% of all cases are potentially cured by surgical resection, while the large majority of cases are deemed either unresectable or metastatic upon diagnosis. Advances in treating locally advanced pancreatic cancer have been few and modest. In this year's American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, three abstracts (#252, #254, #313) were presented with novel approaches towards treating locally advanced pancreatic cancer. Surgery for recurrent disease, a promising new chemoradiation regimen, and the application of an exciting multi-agent regimen (FOLFIRINOX: oxaliplatin, irinotecan, leucovorin, 5-fluorouracil) in a non-clinical trial setting, highlight the novel approaches focused on the management of this difficult disease.

Trends in the treatment of pancreatic cancer in Japan.

Pancreatic cancer is known to have the poorest prognosis among digestive cancers. With the development of new chemotherapeutic agents and introduction of multidisciplinary therapy, however, the treatment outcomes for pancreatic cancer have dramatically improved over the past two decades. The keys to successful treatment will be accurate assessment of resectability [resectable (R), borderline resectable (BR) or unresectable (UR)] at the time of diagnosis and prompt adoption of an appropriate multidisciplinary treatment strategy. Prep-02/JSAP-05 trial which is an RCT of upfront surgery versus neoadjuvant chemotherapy using GEM and S-1 (GS) and subsequent surgery for R-PDAC in Japan indicated neoadjuvant chemotherapy had a longer overall survival (OS) than those undergoing upfront surgery (36.7M vs. 26.6M, p = 0.015). In a retrospective multicenter study in Japan reported that in BR-PDAC, median survival time (MST) in the pretreatment group was significantly better than that in the upfront surgery group (25.7 months vs. 19.0 months, p = 0.015) according to a propensity score matching analysis. Another retrospective multicenter study with UR-LA PDAC in Japan reported that conversion surgery was more beneficial for patients with more than 8 months of preoperative therapy than those with less than 8 months of that therapy. Various clinical trials on pancreatic cancer are ongoing, and the results of trials on chemotherapeutic regimens and multidisciplinary treatments will be of further interest.