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.

Neoadjuvant Therapy for Locally Advanced Rectal Cancer: Recent Advances and Ongoing Challenges.

Locally advanced rectal cancer has a rising global incidence. Over the last 4 decades, advances first in surgery and later in radiotherapy and chemoradiotherapy have improved outcomes, particularly with regard to local recurrence. Unfortunately, distant metastases remain a significant problem. In clinical trials of patients with stage II and III disease, distant relapse occurs in 25% to 30% of patients regardless of the treatment approach. Recent phase 3 trials have therefore focused on intensification of systemic therapy for localized disease, with an aim of reducing the distant relapse rate. Early results of trials of total neoadjuvant therapy with combination systemic therapy provided in the neoadjuvant setting are promising; for the first time, a significant improvement in the rate of distant relapse has been noted. Longer-term follow-up is eagerly awaited. On the other hand, trimodal therapy with chemotherapy, radiotherapy, and surgery is toxic. Several trials are currently assessing the feasibility of a watch-and-wait approach, omitting surgery in those with complete response to neoadjuvant treatment, in an attempt to reduce the burden of treatment on patients. The future for rectal cancer patients is likely to be highly personalized, with more intense approaches for high-risk patients and omission of unnecessary therapy for those whose disease responds well to initial treatment. Biomarkers such as circulating tumor DNA will help to more accurately stratify patients into risk groups. Improvements in survival and quality of life are expected as the results of ongoing research become available throughout the next decade.

Evolving multidisciplinary treatment of squamous cell carcinoma of the head and neck in India✰.

In this article, we highlight the evolution of a multimodal approach in the overall management of squamous cell carcinoma of the head and neck (SCCHN) in India; present advances in technology (newer surgical techniques), novel medical and radiotherapy (RT) approaches; review their roles for an integrated approach for treating SCCHN and discuss the current role of immunotherapy in SCCHN. For locally advanced (LA) SCCHN, the multidisciplinary approach includes surgery followed by RT, with or without chemotherapy (CT) or concurrent chemoradiotherapy. Improved surgical techniques of reconstruction and voice-preservation are being implemented. Advanced forms of high-precision conformal techniques like intensity-modulated radiotherapy are used to deliver highly conformal doses to tumors, sparing the surrounding normal tissue. Compared with RT alone, novel CT regimens and targeted therapeutic agents have the potential to improve locoregional control and survival and reduce treatment-induced toxicities. Several clinical trials have demonstrated efficacy, safety, and quality of life benefits of adding cetuximab to RT regimens in LASCCHN. Studies have also suggested a cetuximab-related laryngeal preservation benefit. At progression, platinum-based CT combined with cetuximab (a monoclonal anti-epidermal growth factor receptor antibody) is the only validated option available as the first-line therapy. Thus, an integrated multidisciplinary approach plays a key role in maximizing patient outcomes, reduction in treatment related morbidities that consequently impact quality of life of survivors.

Impact of multikinase inhibitor approval on survival and physician practice patterns in advanced or metastatic medullary thyroid carcinoma.

BACKGROUND: This study aimed to identify whether multikinase inhibitor approval for medullary thyroid carcinoma was associated with changes in systemic therapy administration or overall survival. METHODS: The National Cancer Database was queried for advanced medullary thyroid carcinoma patients. Clinicopathologic comparisons were performed between premultikinase inhibitor (2005-2010) and postmultikinase inhibitor (2011-2016) approval groups. Multivariable logistic and Cox regressions were applied to assess predictors of systemic therapy and overall survival. RESULTS: A total of 2,891 patients met the criteria. Postmultikinase inhibitor patients were less likely to undergo radiation (P = .02) and more likely to receive systemic therapy (P = .01). The rate of systemic therapy nearly doubled from 2010 to 2011 (8.1% to 13.8%, P = .04); it subsequently declined back toward preapproval rates. Before multikinase inhibitor approval, only metastases and radiation were associated with systemic therapy (P < .05). After multikinase inhibitor approval, patients with small tumors, extrathyroidal extension, positive lymph nodes, or metastases were more likely to receive systemic therapy (P < .05). The 5-year overall survival between pre and postmultikinase inhibitor groups, for those who received systemic therapy (n = 288), was similar (P = .58), even when restricted to patients with distant metastases (P = .55). CONCLUSION: After approval of multikinase inhibitors, physicians broadened the criteria for systemic therapy. Prescription rates have since declined. Given the toxicities of these drugs and no improvement in overall survival since introduction, selective utilization may be warranted.

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.

Axillary surgery for breast cancer: past, present, and future.

In breast cancer surgery, there has been a major shift toward less invasive local treatment. Although axillary lymph node dissection (ALND) was an integral part of surgical treatment for breast cancer, sentinel lymph node (SLN) biopsy was developed as an accurate method for axillary staging. ALND can be avoided not only in patients with negative SLNs but also in those with one or two positive SLNs receiving breast and/or axillary radiation. On the other hand, ALND has remained the standard treatment for patients with clinically positive nodes. However, axillary reverse mapping (ARM) was developed to map and preserve arm lymphatic drainage during ALND and/or SLN biopsy. This procedure allowed reduction of the rate of arm lymphedema without increasing axillary recurrence, although patients receive postoperative chemotherapy and high-risk patients undergo axillary radiation. Standard ALND may not be necessary even for patients with clinically positive nodes who receive axillary radiation and systemic therapy. Thus, the extent of axillary surgery in breast cancer has been decreased with increased use of systemic and radiation therapy.

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.

Trends in Treatment Strategies and Comparison of Outcomes in Lymph Node Positive Bladder Cancer: An Analysis of the National Cancer Database.

OBJECTIVE: To utilize a national dataset to compare outcomes and demonstrate trends in treatment for lymph node positive bladder cancer (N+ BC). METHODS: The National Cancer Database (2006-2014) was queried for cT2-4N1-3M0 N+ BC patients treated with radical cystectomy alone (RC), neoadjuvant chemotherapy (NAC), adjuvant chemotherapy (AC), chemoradiation (CRT), chemotherapy alone (CT), or no definitive treatment (NT). Survival by treatment was analyzed using Kaplan-Meier and multivariable Cox-proportional hazards regression. Pathologic down-staging was analyzed using univariable and multivariable logistic regression models. A univariable logistic regression model of treatment by year identified treatment trends. RESULTS: Among 3241 patients (cN1, 46%; cN2, 44%; cN3 10%), the majority underwent combined chemotherapy and RC (NAC, 418; AC, 591; RC, 567; CRT, 392; CT, 1068; NT, 205). Overall survival did not differ between NAC and AC, but both had improved survival compared to RC. All other treatment groups had worse survival outcomes compared to NAC. Down-staging to pT0 (adjusted odds ratio = 26.39) and pN0 (adjusted odds ratio = 6.88) was higher for NAC than RC. Utilization of NAC has increased, AC and RC has declined, and CRT and NT is unchanged. CONCLUSION: Combined chemotherapy and RC demonstrates best survival outcomes for N+ BC, with complete pathologic response to pT0N0 after NAC associated with a 5-year overall survival rate of ∼85%. However, there is no significant difference between NAC and AC. CRT is associated with worse oncologic outcomes compared to RC with perioperative chemotherapy, but improved survival compared to RC or CT.

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.

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.

Long-term outcomes of surgical resection with or without adjuvant therapy for treatment of primary spinal peripheral primitive neuroectodermal tumors.

OBJECTIVE: We sought to assess the use of surgical treatment, the effect of postoperative adjuvant therapy, and the prognostic factors for survival of patients with primary spinal peripheral primitive neuroectodermal tumors (pPNETs). PATIENTS AND METHODS: The clinical data of 24 patients, who had been surgically treated from April 2003 to February 2018 and in whom immunohistochemical staining results had confirmed the diagnosis of primary spinal pPNETs, were retrospectively analyzed. To analyze the factors related to prognosis, the Kaplan-Meier method was used for univariate analysis, the log-rank method was used to test the significance of difference, and multivariate analysis was performed using Cox regression. RESULTS: The overall 1-year, 2-year, and 5-year survival rates were 73.2%, 48.1%, and 12.0%, respectively. The median survival time (MST) of all patients was 21 months. Univariate analysis showed that the extent of tumor resection, adjuvant radiotherapy, and chemotherapy were the factors influencing patient prognosis after surgery (all P < 0.05); sex, age, tumor location, and preoperative Karnofsky performance scale (KPS) scores were not the influential factors for prognosis of patients after surgery (all P > 0.05). Multivariate analysis showed that gross total resection (GTR) of tumors and adjuvant radiotherapy were independent factors influencing the prognosis of patients with pPNETs (all P < 0.05). CONCLUSIONS: Primary spinal pPNETs are extremely rare, and they have a poor prognosis. Microsurgical GTR of the tumor is the preferred method of treatment. Radiotherapy plays an important role in improving the prognosis of patients with pPNETs. GTR combined with radiotherapy and chemotherapy may be the best treatment modality.

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.

Clinical results of multidisciplinary therapy including palliative posterior spinal stabilization surgery and postoperative adjuvant therapy for metastatic spinal tumor.

BACKGROUND: Surgeries performed for metastatic spinal tumor are mostly palliative and are controversial for patients with short life expectancy. We investigated whether palliative posterior spinal stabilization surgery with postoperative multidisciplinary therapy results in improvement of life prognosis and activities of daily living (ADL) in patients with metastatic spinal tumor. METHODS: The subjects were 55 patients who underwent palliative posterior-only instrumentation surgery for metastatic spinal tumor at our hospital between 2012 and 2015. Postoperative survival, early paralysis improvement, ADL improvement, and rate of discharge to home were examined. RESULTS: The patients included 37 males and 18 females, and the mean age at the time of surgery was 66.8 years old. The mean Tokuhashi score was 7.1, the mean spinal instability neoplastic score (SINS) was 9.4, and the epidural spinal cord compression scale (ESCCS) was grade 3 in 20 patients (36.3%). The mean Barthel index for ADL was 48.7. The median postoperative survival time determined using the Kaplan-Meier method was 12.0 months (95% confidence interval 2.4-21.5). Regarding improvement of paralysis, the modified Frankel scale was improved by one grade or more or grade E was maintained in 35 patients (63.6%), whereas paralysis aggravated in 2 (3.6%). In surgery, conventional posterior decompression and fixation were applied in 31 patients (56.3%), and minimally invasive spine stabilization was applied in 24 (43.6%). Postoperative chemotherapy was performed in 31 patients (56.3%), radiotherapy was used in 38 (69.0%), and a bone-modifying agent was administered in 39 (70.2%). Regarding ADL, the mean Barthel index improved from 48.5 before surgery to 74.5 after surgery. Thirty-seven patients (67.2%) were discharged to home. CONCLUSIONS: ADL improved and allowed discharge to home, and postoperative adjuvant therapy could be administered at a high rate in patients who received palliative posterior spinal stabilization surgery. Survival time extended beyond the preoperative life expectancy in many patients. Patients with a metastatic spinal tumor have short life expectancy and paralysis caused by spinal instability and spinal cord compression. However, multidisciplinary therapy including palliative posterior spinal stabilization surgery with reduced invasiveness and postoperative adjuvant therapy are effective in these patients.

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.

Current trends in multimodality treatment of esophageal and gastroesophageal junction cancer - Review article.

PURPOSE: Multimodality treatment has now been widely introduced in the curatively intended treatment of esophageal and gastroesophageal junction cancer. We aim to give an overview of the scientific evidence for the available treatment strategies and to describe which trends that are currently developing. METHODS: We conducted a review of the scientific evidence for the different curatively intended treatment strategies that are available today. Relevant articles of randomized controlled trials, cohort studies, and meta analyses were included. RESULTS: After a systematic search of relevant papers we have included 64 articles in the review. The results show that adenocarcinomas and squamous cell carcinomas of the esophagus and gastroesophageal junction are two separate entities and should be analysed and studied as two different diseases. Neoadjuvant treatment followed by surgical resection is the gold standard of the curatively intended treatment today. There is no scientific evidence to support the use of chemoradiotherapy over chemotherapy in the neoadjuvant setting for esophageal or junctional adenocarcinoma. There is reasonable evidence to support definitive chemoradiotherapy as a treatment option for squamous cell carcinoma of the esophagus. CONCLUSION: The evidence base for curatively intended treatments of esophageal and gastroesophageal junction cancer is not very strong. Several on-going trials have the potential to change the gold standard treatments of today.

Limited Use of Adjuvant Therapy in Patients With Resected Gallbladder Cancer Despite a Strong Association With Survival.

Background: There are no randomized data to guide clinicians treating patients with gallbladder cancer (GBC). Several retrospective studies reported the survival benefits of adjuvant radiotherapy (RT) and chemoradiation (CRT). In this paper, we examine whether these publications have impacted the utilization of adjuvant therapies and whether their survival benefits are evident in a contemporary cohort of patients. Methods: Using the National Cancer Data Base, we identified 5029 patients diagnosed with T1-3N0-1 GBC and treated with surgical resection from 2005 to 2013. We described trends in receipt of adjuvant treatments for three time periods (2005-2007, 2008-2010, 2011-2013) and calculated three-year overall survival (OS) probabilities for 2989 patients treated in 2005-2010. All statistical tests were two-sided. Results: The percentage of patients who received no adjuvant treatments was unchanged from 2005 to 2013. Adjuvant RT decreased from 4.2% to 1.7% ( P < .001), adjuvant chemotherapy increased from 8.3% to 13.8% ( P < .001), and adjuvant CRT remained stable at 15.9% ( P = .98). Adjuvant treatments were associated with improved three-year OS, with adjusted hazard ratio of 0.47 (95% confidence interval [CI] = 0.39 to 0.58) for CRT, 0.77 (95% CI = 0.61 to 0.97) for chemotherapy, and 0.63 (95% CI = 0.44 to 0.92) for RT. Adjuvant CRT was associated with improved survival in all categories, except T1N0, and in patients with negative and positive margins. Conclusion: Over the past decade there was no increase in the utilization of adjuvant therapies in the United States for patients with resected GBC. Adjuvant therapy is associated with statistically significantly improved three-year OS. This analysis should form the basis for current clinical recommendations and support future prospective trials.

Current Status and Future Prospects for Esophageal Cancer Treatment.

The local control effect of esophagectomy with three-field lymph node dissection (3FLD) is reaching its limit pending technical advancement. Minimally invasive esophagectomy (MIE) by thoracotomy is slowly gaining acceptance due to advantages in short-term outcomes. Although the evidence is slowly increasing, MIE is still controversial. Also, the results of treatment by surgery alone are limiting, and multimodality therapy, which includes surgical and non-surgical treatment options including chemotherapy, radiotherapy, and endoscopic treatment, has become the mainstream therapy. Esophagectomy after neoadjuvant chemotherapy (NAC) is the standard treatment for clinical stages II/III (except for T4) esophageal cancer, whereas chemoradiotherapy (CRT) is regarded as the standard treatment for patients who wish to preserve their esophagus, those who refuse surgery, and those with inoperable disease. CRT is also usually selected for clinical stage IV esophageal cancer. On the other hand, with the spread of CRT, salvage esophagectomy has traditionally been recognized as a feasible option; however, many clinicians oppose the use of surgery due to the associated unfavorable morbidity and mortality profile. In the future, the improvement of each treatment result and the establishment of individual strategies are important although esophageal cancer has many treatment options.

Two countries - Two treatment strategies for rectal cancer.

BACKGROUND AND PURPOSE: Trials in rectal cancer have shown that radiotherapy (RT) decreases local recurrence rates, whereas the effects on survival are uncertain. Swedish and Norwegian oncologists have had different treatment recommendations. The aim was to evaluate local recurrence rates and survival in the two countries. PATIENTS AND METHODS: Between 1995 and 2012 rectal cancer patients registered in Sweden and Norway were analyzed, presenting population-based "real world" data. RESULTS: Totally 29,029 Swedish and 15,456 Norwegian patients were analyzed. Resection for cure was performed in two-thirds of the patients. RT was given to 49% of Swedish patients, mainly short-course RT and to 26% of Norwegian patients, predominantly chemoradiotherapy (CRT). In Sweden, the proportion irradiated was stable whereas in Norway, an increase from 10% to 40% was seen. Local 5-year recurrence rates were initially higher in Norway (12%) than in Sweden (8%), whereas they were equally low (4%) during the latter time. No survival differences were seen, however, survival improved with time in both countries. CONCLUSIONS: Two entirely different approaches to preoperative therapy resulted in similar survival with initially higher local recurrence rates in Norway, but similarly low rates in later years. This raises questions about optimal RT rates and regimens.

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.