Modified FOLFIRINOX in pancreatic cancer patients Age 75 or older.

BACKGROUND: Although FOLFIRINOX (5-Fluorouracil + leucovorin + irinotecan + oxaliplatin) is now the standard of care for patients (pts) with metastatic pancreatic cancer (PC) based on the 2011 study by Conroy et al. which demonstrated improved median overall survival (mOS), pts > 75 yrs old were excluded from this study. The purpose of this study was to assess the safety and efficacy of modified FOLFIRINOX (mFOLFIRINOX) in this population. METHODS: We retrospectively analyzed unresectable PC pts, age ≥ 75, treated with mFOLFIRINOX at MD Anderson from 2011 to 2017. Primary outcome was rate of grade 3 or 4 hematologic toxicity (HT). RESULTS: 24 pts were included. Grade 3 or 4 HT occurred in 11 pts 6 pts required hospitalization for any toxicity, and 10 stopped mFOLFIRINOX due to toxicity. The most frequently used starting doses of infusional 5-FU, irinotecan and oxaliplatin were 2400, 150 and 75 mg/m2, respectively. Median PFS was 3.7 months (95% CI: 3.0-5.7) with a median OS of 11.6 months (95% CI: 6.14-15.7). For first line pts, median PFS and OS were 5.1 (95% CI: 2.0-12.8) and 12.2 months (95% CI: 4.8-30.8), respectively. CONCLUSIONS: In this single-center retrospective analysis of unresectable PC pts age 75 or older given mFOLFIRINOX, toxicities and survival outcomes were similar to those reported in the initial study. These data indicate that the use of modified dosing FOLFIRINOX in advanced PC pts older than 75 appears to maintain similar toxicity and efficacy when compared to younger pts.

Multi-institutional Analysis of Recurrence and Survival After Neoadjuvant Chemoradiotherapy of Esophageal Cancer: Impact of Histology on Recurrence Patterns and Outcomes.

OBJECTIVE: To determine the impact of histology on pathologic response, survival outcomes, and recurrence patterns in patients with esophageal cancer (EC) who received neoadjuvant chemoradiotherapy (CRT). SUMMARY OF BACKGROUND DATA: There is a paucity of data regarding comparative outcomes after neoadjuvant CRT between esophageal squamous cell carcinoma (SCC) and adenocarcinoma. METHODS: Between 2002 and 2015, 895 EC patients who underwent neoadjuvant CRT followed by esophagectomy at 3 academic institutions were retrospectively reviewed, including 207 patients with SCC (23.1%) and 688 patients with adenocarcinoma (76.9%). Pathologic response, survival, recurrence pattern, and potential prognostic factors were compared. RESULTS: Pathologic complete response (pCR) rate was significantly higher for SCC compared with adenocarcinoma (44.9% vs 25.9%, P < 0.001). After a median follow-up of 52.9 months, 71 patients (34.3%) with SCC versus 297 patients (43.2%) with adenocarcinoma had recurrent disease (P = 0.023). For patients who achieved a pCR, no significant differences were found in recurrence pattern, sites, or survival end-points between the 2 histology groups. For non-pCR patients, the SCC group demonstrated significantly higher regional and supraclavicular recurrence rates but a lower hematogenous metastasis rate than adenocarcinoma patients, whereas the adenocarcinoma patients had a more favorable locoregional failure-free survival (P = 0.005) and worse distant metastasis-free survival (P = 0.024). No differences were found in overall survival (P = 0.772) or recurrence-free survival (P = 0.696) between groups. CONCLUSIONS: SCC was associated with a significantly higher pCR rate than adenocarcinoma. Recurrence pattern and survival outcomes were significantly different between the 2 histology subtypes in non-pCR patients.

Laparoscopic Hyperthermic Intraperitoneal Chemotherapy is Safe for Patients with Peritoneal Metastases from Gastric Cancer and May Lead to Gastrectomy.

BACKGROUND: Laparoscopic hyperthermic intraperitoneal chemotherapy (LS-HIPEC) is a novel strategy for patients with gastric adenocarcinoma (GA) metastatic to the peritoneum. We evaluated the safety profile of LS-HIPEC for patients with positive peritoneal cytology (PPC) or carcinomatosis from GA. METHODS: Outcomes were reviewed of patients with stage IV GA with peritoneal involvement who received LS-HIPEC from June 2014 to January 2017. LS-HIPEC included a 60-minute perfusion of mitomycin-C (30 mg) and cisplatin (200 mg) with inflow temperatures of 41-42 °C and outflow temperatures of 39-40 °C. RESULTS: A total of 71 LS-HIPEC procedures were performed in 44 patients. At diagnosis, 68% (n = 30) had carcinomatosis and 32% (n = 14) had isolated PPC. Three patients (7%) underwent LS-HIPEC for intractable ascites. All patients initially received systemic chemotherapy, and 20 patients (45%) received pre-procedural chemoradiotherapy. The median number of LS-HIPEC procedures performed per patient was one (range 1-5 procedures). There were no conversions to laparotomy, two outflow catheter obstructions, and one major (Clavien-Dindo grade III) surgical complication within 30 days. A total of seven postoperative adverse hematologic events (> CTCAE 2) were observed in five patients (11%), without any major renal or gastrointestinal adverse events within 30 days. The median overall length of hospital stay after LS-HIPEC was 2 (range 2-11) days. Eleven patients (25%) underwent secondary gastrectomy following resolution of peritoneal cytology. CONCLUSIONS: Laparoscopic HIPEC is a safe procedure and may be repeated in patients with peritoneal metastases from gastric cancer. Future studies are required to determine the optimal HIPEC regimen and timing relative to systemic therapy to best minimize morbidity.

Recurrence Risk Stratification After Preoperative Chemoradiation of Esophageal Adenocarcinoma.

OBJECTIVE: To discern recurrence risk stratification and investigate its influence on postoperative surveillance in patients with esophageal adenocarcinoma (EAC) after neoadjuvant chemoradiotherapy (CRT). BACKGROUND: Reports documenting recurrence risk stratification in EAC after neoadjuvant CRT are scarce. METHODS: Between 1998 and 2014, 601 patients with EAC who underwent neoadjuvant CRT followed by esophagectomy were included for analysis. The pattern, site, timing, and frequency of the first recurrence and potential prognostic factors for developing recurrences were analyzed. This cohort was used as the training set to propose a recurrence risk stratification system, and the stratification was further validated in another cohort of 172 patients. RESULTS: A total of 150 patients (25.0%) achieved pathologic complete response (pCR) after neoadjuvant CRT and the rest were defined as the non-pCR group (n = 451) in the training cohort. After a median follow-up of 63.6 months, the pCR group demonstrated a significantly lower locoregional (4.7% vs 19.1%) and distant recurrence rate (22.0% vs.44.6%) than the non-pCR group (P < 0.001). Based on independent prognostic factors, patients were stratified into 4 recurrence risk categories: pCR with clinical stage I/II, pCR with clinical stage III, non-pCR with pN0, and non-pCR with pN+, with corresponding 5-year recurrence-free survival rates of 88.7%, 65.8%, 55.3%, and 33.0%, respectively (P < 0.001). The risk stratification was reproducible in the validation cohort. CONCLUSIONS: We proposed a recurrence risk stratification system for EAC patients based on pathologic response and pretreatment clinical stage. Risk-based postoperative surveillance strategies could be developed for different risk categories.

Preoperative Nomogram to Risk Stratify Patients for the Benefit of Trimodality Therapy in Esophageal Adenocarcinoma.

PURPOSE: To develop a nomogram that estimates 1-year recurrence-free survival (RFS) after trimodality therapy for esophageal adenocarcinoma and to assess the overall survival (OS) benefit of esophagectomy after chemoradiotherapy (CRT) on the basis of 1-year recurrence risk. METHODS: In total, 568 consecutive patients with potentially resectable esophageal adenocarcinoma who underwent CRT were included for analysis, including 373 patients who underwent esophagectomy after CRT (trimodality therapy), and 195 who did not undergo surgery (bimodality therapy). A nomogram for 1-year RFS was created using a Cox regression model. The upper tertile of the nomogram score was used to stratify patients in low-risk and high-risk groups for 1-year recurrence. The 5-year OS was compared between trimodality and bimodality therapy in low-risk and high-risk patients after propensity score matching, respectively. RESULTS: Median follow-up for the entire cohort was 62 months. The 5-year OS in the trimodality and bimodality treatment groups was 56.3% (95% confidence interval [CI] 47.9-64.7) and 36.9% (95% CI 31.4-42.4), respectively. The final nomogram for the prediction of 1-year RFS included male gender, poor histologic grade, signet ring cell adenocarcinoma, cN1, cN2-3, and baseline SUVmax, with accurate calibration and reasonable discrimination (C-statistic: 0.66). Trimodality therapy was associated with improved 5-year OS in low-risk patients (p = 0.003), whereas it showed no significant survival benefit in high-risk patients (p = 0.302). CONCLUSIONS: The proposed nomogram estimates early recurrence risk. The addition of surgery to CRT provides a clear OS benefit in low-risk patients. The OS benefit of surgery in high-risk patients is less pronounced.

Prediction and diagnosis of interval metastasis after neoadjuvant chemoradiotherapy for oesophageal cancer using 18F-FDG PET/CT.

OBJECTIVE: During neoadjuvant chemoradiotherapy for oesophageal cancer, or in the interval prior to surgery, some patients develop systemic metastasis. This study aimed to evaluate the diagnostic performance of 18F-FDG PET/CT for the detection of interval metastasis and to identify predictors of interval metastases in a large cohort of oesophageal cancer patients. METHODS: In total, 783 consecutive patients with potentially resectable oesophageal cancer who underwent chemoradiotherapy and pre- and post-treatment 18F-FDG PET/CT between 2006 and 2015 were analyzed from a prospectively maintained database. Diagnostic accuracy measures were calculated on a per-patient basis using histological verification or clinical follow-up as a reference standard. Multivariable logistic regression analysis was performed to determine pre-treatment predictors of interval metastasis. A prediction score was developed to predict the probability of interval metastasis. RESULTS: Of 783 patients that underwent 18F-FDG PET/CT restaging, 65 (8.3%) were found to have interval metastasis and 44 (5.6%) were deemed to have false positive lesions. The resulting sensitivity and specificity was 74.7% (95% CI: 64.3-83.4%) and 93.7% (95% CI: 91.6-95.4%), respectively. Multivariable analysis revealed that tumor length, cN status, squamous cell tumor histology, and baseline SUVmax were associated with interval metastasis. Based on these criteria, a prediction score was developed with an optimism adjusted C-index of 0.67 that demonstrated accurate calibration. CONCLUSIONS: 18F-FDG PET/CT restaging detects distant interval metastases in 8.3% of patients after chemoradiotherapy for oesophageal cancer. The provided prediction score may stratify risk of developing interval metastasis, and could be used to prioritize additional restaging modalities for patients most likely to benefit.

Phase II Trial of Laparoscopic Hyperthermic Intraperitoneal Chemoperfusion for Peritoneal Carcinomatosis or Positive Peritoneal Cytology in Patients with Gastric Adenocarcinoma.

PURPOSE: The aim of this phase II study was to perform neoadjuvant hyperthermic intraperitoneal chemoperfusion (HIPEC) via a minimally invasive approach without cytoreduction for patients with gastric cancer and positive peritoneal cytology or low-volume peritoneal carcinomatosis. METHODS: Patients with gastric or gastroesophageal adenocarcinoma and positive peritoneal cytology or radiologically occult peritoneal carcinomatosis after systemic chemotherapy received laparoscopic HIPEC with mitomycin C 30 mg and cisplatin 200 mg. Patients whose peritoneal disease resolved were offered gastrectomy. The primary endpoint was overall survival (OS), with secondary endpoints of HIPEC complications and gastrectomy rate. RESULTS: We enrolled 19 patients (6 with positive peritoneal cytology only and 13 with peritoneal carcinomatosis) and treated them with 38 laparoscopic HIPEC procedures. Patients had received a median of 8 cycles (range 3-12) of systemic chemotherapy prior to enrollment. Fourteen patients were also treated with chemoradiotherapy before or between cycles of HIPEC. The complication rate for HIPEC was 11% (4 of 38 procedures), the 30-day mortality rate was 0%, and the median length of hospital stay after HIPEC was 3 days (range 2-6). Five patients went on to receive gastrectomy. The median follow-up was 18.9 months, the median OS from the date of diagnosis of metastatic disease was 30.2 months, and the median OS from the first laparoscopic HIPEC was 20.3 months. CONCLUSIONS: Laparoscopic HIPEC was well tolerated, and an encouraging number of patients demonstrated an absence of peritoneal disease after HIPEC and were able to undergo gastrectomy. Comparative studies will be required to clarify survival benefits.

The value of 18F-FDG PET before and after induction chemotherapy for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy in oesophageal adenocarcinoma.

PURPOSE: The purpose of our study was to determine the value of 18F-FDG PET before and after induction chemotherapy in patients with oesophageal adenocarcinoma for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy (CRT). METHODS: In 70 consecutive patients receiving a three-step treatment strategy of induction chemotherapy and preoperative chemoradiotherapy for oesophageal adenocarcinoma, 18F-FDG PET scans were performed before and after induction chemotherapy (before preoperative CRT). SUVmax, SUVmean, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were determined at these two time points. The predictive potential of (the change in) these parameters for a poor pathologic response, progression-free survival (PFS) and overall survival (OS) was assessed. RESULTS: A poor pathologic response after induction chemotherapy and preoperative CRT was found in 27 patients (39 %). Patients with a poor pathologic response experienced less of a reduction in TLG after induction chemotherapy (p < 0.01). The change in TLG was predictive for a poor pathologic response at a threshold of -26 % (sensitivity 67 %, specificity 84 %, accuracy 77 %, PPV 72 %, NPV 80 %), yielding an area-under-the-curve of 0.74 in ROC analysis. Also, patients with a decrease in TLG lower than 26 % had a significantly worse PFS (p = 0.02), but not OS (p = 0.18). CONCLUSIONS: 18F-FDG PET appears useful to predict a poor pathologic response as well as PFS early after induction chemotherapy in patients with oesophageal adenocarcinoma undergoing a three-step treatment strategy. As such, the early 18F-FDG PET response after induction chemotherapy could aid in individualizing treatment by modification or withdrawal of subsequent preoperative CRT in poor responders.

Radiation modality use and cardiopulmonary mortality risk in elderly patients with esophageal cancer.

BACKGROUND: It is currently unclear whether the superior normal organ-sparing effect of intensity-modulated radiotherapy (IMRT) compared with 3-dimensional radiotherapy (3D) has a clinical impact on survival and cardiopulmonary mortality in patients with esophageal cancer (EC). METHODS: The authors identified 2553 patients aged > 65 years from the Surveillance, Epidemiology, and End Results (SEER)-Medicare and Texas Cancer Registry-Medicare databases who had nonmetastatic EC diagnosed between 2002 and 2009 and were treated with either 3D (2240 patients) or IMRT (313 patients) within 6 months of diagnosis. The outcomes of the 2 cohorts were compared using inverse probability of treatment weighting adjustment. RESULTS: Except for marital status, year of diagnosis, and SEER region, both radiation cohorts were well balanced with regard to various patient, tumor, and treatment characteristics, including the use of IMRT versus 3D in urban/metropolitan or rural areas. IMRT use increased from 2.6% in 2002 to 30% in 2009, whereas the use of 3D decreased from 97.4% in 2002 to 70% in 2009. On propensity score inverse probability of treatment weighting-adjusted multivariate analysis, IMRT was not found to be associated with EC-specific mortality (hazard ratio [HR], 0.93; 95% confidence interval [95% CI], 0.80-1.10) or pulmonary mortality (HR, 1.11; 95% CI, 0.37-3.36), but was significantly associated with lower all-cause mortality (HR, 0.83; 95% CI, 0.72-0.95), cardiac mortality (HR, 0.18; 95% CI, 0.06-0.54), and other-cause mortality (HR, 0.54; 95% CI, 0.35-0.84). Similar associations were noted after adjusting for the type of chemotherapy, physician experience, and sensitivity analysis removing hybrid radiation claims. CONCLUSIONS: In this population-based analysis, the use of IMRT was found to be significantly associated with lower all-cause mortality, cardiac mortality, and other-cause mortality in patients with EC.

Postoperative Morbidity and Mortality Rates are Not Increased for Patients with Gastric and Gastroesophageal Cancer Who Undergo Preoperative Chemoradiation Therapy.

BACKGROUND: This study aimed to determine whether postoperative morbidity and mortality rates increased after preoperative chemoradiation in patients who underwent gastrectomy. METHODS: The medical records of 7404 patients with gastric or gastroesophageal cancer seen from January 1995 to August 2012 were reviewed to identify patients who underwent gastrectomy. χ (2) and logistic regression analysis were used to determine differences in the 90-day postoperative morbidity and mortality rates of patients who underwent upfront surgery (SURG), preoperative chemotherapy (CHEMO), or preoperative chemoradiation (CHEMOXRT). RESULTS: Of the 500 patients included in this study, 200 underwent SURG, 65 had CHEMO, and 235 had CHEMOXRT. Respectively, 33, 43, and 58 % of these patients underwent total gastrectomy (p < 0.01). Resection of other organs was performed respectively in 19, 26, and 23 % of the patients (p = 0.37). Minor complications within 90 days (Clavien-Dindo 1 or 2) occurred for 41 % of the SURG patients, 43 % of the CHEMO patients, and 45 % of the CHEMOXRT patients (p = 0.68). Major complications or death within 90 days (Clavien-Dindo 3, 4, or 5) occurred for 21, 28, and 29 % of the patients, respectively (p = 0.15). The 90-day mortality (Clavien-Dindo 5) rates were 2 % for the SURG patients, 6 % for the CHEMO patients, and 3 % for the CHEMOXRT patients (p = 0.25). The median hospital stays were respectively 12, 12, and 13 days (p = 0.09). In the multivariate analysis, male sex, gastroesophageal junction cancer, total gastrectomy, and resection of other organs were associated with increased major morbidity and mortality rates, whereas preoperative therapy was not. CONCLUSIONS: The CHEMOXRT patients had postoperative morbidity and mortality rates similar to those for the SURG and CHEMO patients.

Impact of comorbidities and use of common medications on cancer and non-cancer specific survival in esophageal carcinoma.

BACKGROUND: Chronic comorbidities and some of the commonly-used medications are thought to affect cancer patients' outcomes, but their relative impact on esophageal carcinoma (EC) has not been well studied. The purpose of the study was to identify the chronic comorbidities and/or commonly-used medications that impact EC patient survival. METHODS: A total of 1174 EC patients treated with chemoradiotherapy (CRT) with or without surgery in one institution from 1998 to 2012 were retrospectively included. Seven kinds of frequently occurring chronic comorbidities and 18 types of regularly-taken medications were obtained from medical records. Since it is expected prognostic factors have different effects between surgery patients and non-surgery patients, the impact value of all variables and the corresponding interactions with surgery on survival were evaluated in Cox proportional hazards regression model. Overall mortality, EC-specific mortality and non EC-specific mortality were endpoints. RESULTS: We found that atrial fibrillation was the only comorbidity that showed a significant impact on non-EC specific survival for all patients (HR 1.72, P = 0.03), whereas hypothyroidism was the only comorbidity that was evaluated as an independent predictive factor for overall survival (OS) (HR 0.59, P = 0.02) and EC-specific survival (HR 0.62, P = 0.05), but this association was seen only in the non-surgical patients. No other medications were found to have a significant impact for OS, EC-specific survival or non-EC specific survival in multivariable analysis. CONCLUSIONS: Our data indicate that certain comorbidities rather than medication use affect EC-specific survival or non EC-specific survival in EC patients treated with CRT with or without surgery. Comorbidity information may better guide individual treatment in EC.

Benefit of Gemcitabine/Nab-Paclitaxel Rescue of Patients With Borderline Resectable or Locally Advanced Pancreatic Adenocarcinoma After Early Failure of FOLFIRINOX.

OBJECTIVES: Neoadjuvant therapy (NT) is used for advanced pancreatic ductal adenocarcinoma (PDAC). No clear guidelines exist for switching therapies when patients do not respond to initial NT. We sought to characterize patients who underwent early switch from FOLFIRINOX to gemcitabine/nab-paclitaxel (GA) as NT for PDAC. METHODS: We identified patients at a single institution switched from FOLFIRINOX to GA within the first 4 months of NT for PDAC during 2012-2017. We compared clinicopathologic data and oncologic outcomes. RESULTS: Of 25 patients who met the criteria, 21 showed a serologic or radiographic response to GA; 11 (52%) reached resection. Responders had decreased carbohydrate antigen (CA) 19-9 levels from pretreatment to post-GA (P = 0.036). Resected responders had significantly decreased CA 19-9 comparing preswitch to post-GA (P = 0.048). The only predictor of GA response was prechemotherapy CA 19-9 of less than1000 U/mL (P = 0.021). Predictors of reaching resection were head/uncinate tumor (P = 0.010) and presenting stage lower than locally advanced (P = 0.041). CONCLUSIONS: When patients do not respond to neoadjuvant FOLFIRINOX, early switch to GA should be considered. Future efforts should be directed toward identifying markers that will allow correct choice of initial therapy rather than attempting to rescue patients who respond poorly to first-line therapy.

A Phase I/II Study of Docetaxel, Oxaliplatin, and Fluorouracil (D-FOX) Chemotherapy in Patients With Untreated Locally Unresectable or Metastatic Adenocarcinoma of the Stomach and Gastroesophageal Junction.

BACKGROUND: A randomized phase III study established docetaxel, cisplatin, and 5-fluorouracil (DCF) as one of the standard treatments for patients with untreated advanced gastric cancer (AGC). However, DCF use is limited due toxicity. With the purpose to evaluate a less toxic regimen, we conducted a single arm, phase I/II trial of modified DCF (oxaliplatin, 5-fluorouracil, and docetaxel [D-FOX]) for untreated AGC patients. The primary objective of the phase I study was to determine the maximum tolerated dose of docetaxel and for the phase II study was to assess the progression-free survival (PFS) at 6 months and overall survival (OS). PATIENTS AND METHODS: We enrolled a total of 98 patients with AGC. Docetaxel and oxaliplatin were administered intravenously on day 1 and 5-fluorouracil was infused starting on day 1 over 48 hours. Cycles were repeated every 2 weeks and patients were monitored for toxicities. Kaplan-Meir curve was used to estimate unadjusted OS and PFS. RESULTS: The maximum tolerated dose of docetaxel was 50 mg/m. In total, 24 (45%) patients experienced grade 2 adverse events, 22 (41%) experienced grade 3, and 1 (1.9%) experienced grade 4 toxicity. The median PFS in the phase II portion of the study was approximately 6.5 (95% confidence interval, 5.5-9.5) months and the median OS was 11.1 (95% confidence interval, 9.4-18.8) months. CONCLUSIONS: D-FOX administered every 2 weeks is a well-tolerated and active regimen in untreated AGC patients.

Systemic chemotherapy and two-stage hepatectomy for extensive bilateral colorectal liver metastases: perioperative safety and survival.

BACKGROUND: Two-stage hepatectomy has been proposed for patients with bilateral colorectal liver metastases (CLM). The aim of this study was to compare the outcome of patients with CLM treated with preoperative chemotherapy followed by one- or two-stage hepatectomy. METHODS: From a prospective database, 214 consecutive patients who received preoperative systemic chemotherapy (fluoropyrimidine with irinotecan or oxaliplatin) followed by planned one- or two-stage hepatectomy were retrospectively analyzed (1998-2006). In patients undergoing two-stage procedures, minor hepatectomy (wedge or segmental resection[s]) was systematically performed before major (more than three segments), second-stage hepatectomy. Preoperative portal vein embolization (PVE) was performed if indicated. RESULTS: One- (group I) and two-stage (group II) hepatectomies were performed in 184 and 21 patients, respectively. Median number of metastases in groups I and II were two (range 1-20) and seven (range 2-20). All patients in group II had bilateral disease vs 39% in group I. Major hepatectomy was performed in all patients in group II and 79% in group I. PVE was performed in 18 group I and 12 group II patients without increase in morbidity. For group I, group II first stage, and group II second stage, respectively, morbidity (24%, 24%, 43%), median hospital stay (7 days, 6 days, 6.5 days) and 30 days postoperative mortality (2%, 0%, 0%) were not significantly different (P = NS). Median follow-up was 25 months; median survival has not been reached. One- and 3-year overall and disease-free survival rates from the time of hepatic resection were 95% and 75%, 63% and 39%, respectively in group I; 95% and 86%, 70% and 51%, respectively in group II (P = NS). CONCLUSIONS: Two-stage hepatectomy with preoperative chemotherapy results in comparable morbidity and survival rates as one-stage hepatectomy. This approach enables selection and treatment of patients with multiple, bilateral CLM who will benefit from aggressive surgery with good outcomes.

Patterns of self-reported symptoms in pancreatic cancer patients receiving chemoradiation.

Pancreatic cancer is a lethal disease characterized by multiple disease-related symptoms. Chemoradiation therapy is a standard of treatment for locally advanced pancreatic cancer. Although shown to prolong survival, there is little information about treatment-related symptoms or the palliative benefits of chemoradiation. We assessed symptoms of patients with locally advanced pancreatic cancer receiving chemoradiation to determine the prevalence, and co-occurrence, of symptoms and to identify the extent to which symptoms interfered with function. Forty-eight patients were treated with chemoradiation on a Phase I protocol. Patients received radiotherapy (50.4 Gy in 28 fractions), capecitabine (median dose 825 mg/m(2) twice daily), and bevacizumab (2.5-10 mg/kg). Symptom severity and its interference with function were prospectively assessed (at presentation, during, and after chemoradiation) in 43 consenting patients using the M.D. Anderson Symptom Inventory. Results showed that 95% of patients reported at least one of the 13 symptoms assessed at presentation. The most commonly reported symptoms of moderate to severe (>or=5 on a 0-10 scale) intensity at presentation were lack of appetite (24%), pain (19%), fatigue (19%), and sleep disturbance (10%). We observed an increase in patients reporting moderate to severe fatigue, nausea, and sleep disturbance during chemoradiation. McNemar tests for paired binary observations showed the proportion of patients reporting moderate to severe symptoms significantly (P<0.001) decreased after chemoradiation at 94 days follow-up (lack of appetite=7%, pain=7%, fatigue=13%, sleep disturbance=7%). This study demonstrates the feasibility and usefulness of symptom assessment in chemoradiation protocols. Future studies with larger cohorts are needed to further characterize multiple symptoms associated with chemoradiation.

Recursive Partitioning Analysis Identifies Pretreatment Risk Groups for the Utility of Induction Chemotherapy Before Definitive Chemoradiation Therapy in Esophageal Cancer.

PURPOSE: To assess the contribution of induction chemotherapy (IC) before definitive chemoradiation therapy (dCRT) in patients with esophageal cancer (EC) based on recursive partitioning analysis (RPA). METHODS AND MATERIALS: A total of 496 eligible patients with EC staged by positron emission tomography (PET) who received dCRT from 1998 to 2015 were included, 162 (32.7%) of whom underwent IC before dCRT. RPA was used to risk-stratify patients on the basis of independent prognostic factors to predict progression-free survival (PFS). Outcomes were compared between treatment groups. RESULTS: The median follow-up time was 49.1 months (range, 7.0-155.9 months) for survivors. Compared with the non-IC group, the IC group had a comparable 5-year PFS rate (21.0% vs 23.4%; P=.726) in the whole cohort. Multivariate analysis identified age, performance status, primary tumor length, baseline PET maximum standard uptake value (SUVmax), and maximum lymph node diameter as independent prognostic factors for PFS. RPA segregated patients into 3 prognostic groups: low-risk group (PET SUVmax <9.7 and tumor length ≤5 cm), intermediate-risk group (PET SUVmax ≥9.7 and age ≥67), and high-risk group (PET SUVmax <9.7 and tumor length >5 cm, or PET SUVmax ≥9.7 and age <67). Significant improvements in PFS (P=.006) and locoregional failure-free survival (P=.028) in the IC group in comparison with the non-IC group were observed in high-risk patients, whereas no differences in survival were found between the 2 treatment groups in low-risk or intermediate-risk patients. After propensity score matching, the high-risk group still demonstrated a significantly improved PFS with IC (P=.009). CONCLUSIONS: The RPA prognostic grouping provides a useful method of selecting high-risk EC patients who may benefit from IC before receiving dCRT. Prospective validation is warranted.

18F-FDG PET Response After Induction Chemotherapy Can Predict Who Will Benefit from Subsequent Esophagectomy After Chemoradiotherapy for Esophageal Adenocarcinoma.

This study aimed to determine whether 18F-FDG PET response after induction chemotherapy before concurrent chemoradiotherapy can identify patients with esophageal adenocarcinoma who may benefit from subsequent esophagectomy. Methods: We identified and analyzed 220 patients with esophageal adenocarcinoma who had received induction chemotherapy before chemoradiotherapy, with or without surgery, with curative intent; all underwent 18F-FDG PET scanning before and after induction chemotherapy. 18F-FDG PET responders were defined as patients who achieved complete response (CR) after induction chemotherapy (maximum SUV ≤ 3.0). The predictive value of 18F-FDG PET response for patient outcomes was evaluated. Results: Overall, 86 patients had bimodality therapy (BMT; induction chemotherapy + chemoradiotherapy) and 134 had trimodality therapy (TMT; induction chemotherapy + chemoradiotherapy with surgery). Forty-eight patients (21.8%) achieved an 18F-FDG PET CR after induction chemotherapy. 18F-FDG PET CR was found to correlate with overall survival (OS) and progression-free survival (PFS) in BMT patients. For TMT patients, 18F-FDG PET CR predicted pathologic response (P = 0.003) but not survival. Among 18F-FDG PET nonresponders, TMT patients had significantly better survival than did BMT patients (P < 0.001). However, among 18F-FDG PET responders, BMT patients had OS (P = 0.201) and PFS (P = 0.269) similar to that of TMT patients. After propensity score-matched analysis, 18F-FDG PET responders treated with BMT versus TMT still had comparable OS and PFS, but TMT was associated with better locoregional control. Conclusion:18F-FDG PET response to induction chemotherapy could be a useful imaging biomarker to identify patients with esophageal adenocarcinoma who could benefit from subsequent esophagectomy after chemoradiotherapy. Compared with BMT, TMT can significantly improve survival in 18F-FDG PET nonresponders. However, outcomes for 18F-FDG PET responders were similar after either treatment (BMT or TMT). Prospective validation of these findings is warranted.

A Prognostic Scoring Model for the Utility of Induction Chemotherapy Prior to Neoadjuvant Chemoradiotherapy in Esophageal Cancer.

OBJECTIVES: The aim of this study was to identify patients with esophageal cancer who may benefit from induction chemotherapy (IC) before neoadjuvant chemoradiotherapy (nCRT) on the basis of a prognostic scoring model. METHODS: Between 1998 and 2015, 535 patients with esophageal cancer who underwent nCRT were included for analysis, including 218 patients who received IC before nCRT (IC group) and 317 patients who did not receive IC (non-IC group). A prognostic scoring model was developed to predict disease-free survival (DFS) on the basis of a Cox proportional hazards model. RESULTS: The median follow-up time was 63.5 months (range 8.0-178.5) for survivors. The 5-year DFS rates were similar between the IC and non-IC groups (53.7% vs. 45.1%, p = 0.196). Multivariate analysis determined that histologic grade, tumor location, baseline positron emission tomography maximum standard uptake value, and lymph node size were independent prognostic factors for DFS. A prognostic scoring system was constructed by using these four factors, with the total score ranging from 0 to 6.2. When the median value was used as a cutoff, low-risk (≤3.5) and high-risk (>3.5) groups were identified. In the high-risk group, patients who received IC had a nonsignificantly higher pathologic complete response rate (p = 0.272) and a significantly better DFS (p = 0.03) than patients who did not receive IC. After propensity score matching, the high-risk group demonstrated a significantly improved DFS with IC, a benefit that was not observed in the low-risk group. CONCLUSIONS: On the basis of the prognostic scoring model, the addition of IC to nCRT may provide a DFS benefit in high-risk patients with a risk score higher than 3.5. Prospective validation is warranted.

Long-term survival and toxicity outcomes of intensity modulated radiation therapy for the treatment of esophageal cancer: A large single-institutional cohort study.

PURPOSE: In patients with esophageal cancer (EC), intensity modulated radiation therapy (IMRT) improves dose sparing to the heart and lung, with some evidence showing clinical benefit. Herein, we report our cumulative clinical experience with the use of IMRT for EC. METHODS AND MATERIALS: This is a retrospective analysis of 587 patients with nonmetastatic EC who were treated consecutively with IMRT from January 2004 to June 30, 2013. All patients with stage I-IVA (American Joint Committee on Cancer 2002) received concurrent chemoradiation therapy either preoperatively or definitively. The Kaplan-Meier method was used to compute overall survival (OS) and locoregional recurrence-free survival and disease-free survival. The Common Terminology Criteria for Adverse Events, Version 4.0 were used to grade acute and subacute complications. RESULTS: The median radiation dose was 50.4 Gy in 28 daily fractions. As of July 2015, the median follow-up was 31.4 months (range, 2.9-130.7 months) for all patients and 61.8 months (range, 7.7-130.7 months) for survivors. The median OS was 38.9 months, and the 1-, 3-, and 5-year OS rates were 86.7%, 51.8%, and 41.2%, respectively. The 1-, 3-, and 5-year locoregional recurrence-free survival rates were 77.6%, 68.2%, and 66.1%, respectively, and the 1-, 3-, and 5-year disease-free survival rates were 58.6%, 43.7%, and 41.4%, respectively. Outcomes for both trimodality and bimodality treated patients were better than the outcomes reported in the literature. Eight patients (1.4%) experienced grade ≥3 pneumonitis, and 74 patients (13%) developed grade ≥3 esophagitis. For patients who underwent surgery, the most common postoperative complications were pneumonia (9.6%), anastomotic leakage (11.1%), and atrial fibrillation (12.5%). CONCLUSIONS: This is the largest, single institutional study to date on the long-term outcomes of treatment with IMRT for EC. For photon-based radiation therapy, IMRT yields excellent outcomes and should be considered for the treatment of EC.

Factors Predictive of Improved Outcomes With Multimodality Local Therapy After Palliative Chemotherapy for Stage IV Esophageal Cancer.

OBJECTIVES: We reviewed survival outcomes and factors associated with improved outcomes for patients with stage IVB esophageal cancer who received multimodality therapy with initial chemotherapy followed by concurrent chemoradiation (CRT)±surgery. METHODS: We retrospectively identified 96 patients with stage IVB esophageal carcinoma (with positive nonregional lymph nodes and/or distant organ metastasis) treated at a single institution with chemotherapy followed by concurrent CRT, with or without surgery. The Cox proportional hazard model was used to test associations between overall survival (OS), disease-free survival (DFS), locoregional relapse, distant metastasis-free survival, and potential predictive factors. RESULTS: Median patient age at diagnosis was 59 years. The median OS time among all patients was 21.0 months, and 1-, 2-, and 5-year OS rates were 84.4%, 46.8%, and 17.9%, respectively; corresponding DFS time and rates were 8.1 months and 37%, 24.6%, and 24.6%, respectively. On multivariate analysis, factors that predicted improved OS with aggressive multimodal therapy included young age; lack of anorexia, fatigue at diagnosis; distant nodal metastasis without organ metastasis at diagnosis; and radiographic response to initial chemotherapy. A subset of 14 patients who had surgery after chemotherapy and concurrent CRT also had better median OS (not reached vs. 20 mo for 82 patients who did not receive surgery, P=0.001), DFS (14.6 vs. 5.9 mo, P=0.021), and distant metastasis-free survival (26.7 vs. 9.2 mo, P=0.042). CONCLUSIONS: Aggressive local therapy with radiation and potentially surgery after initial palliative chemotherapy can improve prognosis for a select group of patients with stage IVB esophageal cancer.