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Treatment of locally advanced unresectable or metastatic cutaneous squamous cell carcinoma (mCSCC) is suboptimal with a paucity of robust data on systemic therapy. This retrospective study aimed to evaluate the efficacy and outcomes of patients with locally advanced unresectable or mCSCC treated with systemic therapy.Records of patients with CSCC treated with systemic therapy from January 2001 to January 2011 were reviewed. Response was assessed using WHO criteria. Descriptive results were assessed using Wilcoxon rank-sum test for ordinal responses and Pearson χ test for categorical responses. Survival was calculated by the Kaplan-Meier method.Of 28 patients identified, 25 patients (M:F=18:7), median age 66 years (range, 39 to 85 y), had the required data for final analysis. Partial response was 44% and stable disease (SD) was 24%. The median progression-free survival (PFS) and overall survival (OS) were 5.5 months (2.3, 13.2) and 10.9 months (5.3, 21.3) respectively; 3-year OS was 22%. Patients with WHO response had improved PFS (20.8 mo; 4.4, NR) and OS (37.5 mo; 10.3, NR) compared with patients with SD/PD (PFS 2.7 mo; OS 5.9 mo). Use of platinum-based therapy significantly improved PFS and OS, whereas taxanes and cetuximab had no impact in this small cohort. There was no difference in PFS or OS with multiagent versus single-agent therapy.Platinum-based therapy remains as one of the standard options in advanced CSCC management. Agents to improve response rates are needed and future trials should address the use of novel targeted and new chemotherapy combinations in CSCC.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer begin with the clinical presentation of the patient to the primary care physician or gastroenterologist and address diagnosis, pathologic staging, surgical management, perioperative treatment, patient surveillance, management of recurrent and metastatic disease, and survivorship. The NCCN Colon Cancer Panel meets annually to review comments from reviewers within their institutions and to reevaluate and update their recommendations. In addition, the panel has interim conferences as new data necessitate. These NCCN Guidelines Insights summarize the NCCN Colon Cancer Panel's discussions surrounding metastatic colorectal cancer for the 2013 update of the guidelines. Importantly, changes were made to the continuum of care for patients with advanced or metastatic disease, including new drugs and an additional line of therapy.

The workup and management of squamous cell anal carcinoma, which represents the most common histologic form of the disease, are addressed in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Anal Carcinoma. These NCCN Guidelines Insights provide a summary of major discussion points of the 2012 NCCN Anal Carcinoma Panel meeting. In summary, the panel made 4 significant changes to the 2012 NCCN Guidelines for Anal Carcinoma: 1) local radiation therapy was added as an option for the treatment of patients with metastatic disease; 2) multifield technique is now preferred over anteroposterior-posteroanterior (AP-PA) technique for radiation delivery and the AP-PA technique is no longer recommended as the standard of care; 3) PET/CT should now be considered for radiation therapy planning; and 4) a section on risk reduction was added to the discussion section. In addition, the panel discussed the use of PET/CT for the workup of anal canal cancer and decided to maintain the recommendation that it can be considered in this setting. They also discussed the use of PET/CT for the workup of anal margin cancer and for the assessment of treatment response. They reaffirmed their recommendation that PET/CT is not appropriate in these settings.

Cancers of the esophagus, stomach, and the esophagogastric junction (EGJ) remain a global health problem. There has been a dramatic increase in the incidence of adenocarcinoma of the distal esophagus and EGJ in the past two decades with little change in the poor prognosis associated with these cancers. Previously surgery alone was the mainstay of therapeutic intervention, but high rates of local and systemic failure have prompted investigation into neoadjuvant and adjuvant therapy. Treatment paradigms differ across continents, but the unifying theme that has emerged in the past decade implies that surgery alone can no longer be considered the standard of care. The multi-disciplinary management of patients with locally advanced esophagogastric carcinomas using trimodality therapy with radiotherapy, chemotherapy, and surgery confers the greatest opportunity for margin negative resection, improved loco-regional control and cure, and should be the accepted treatment paradigm. The traditional backbone of platinum plus fluorouracil concurrent with radiotherapy may be supplanted by more modern, easier-to-administer regimens incorporating taxanes and irinotecan. The current generation of clinical trials in this heterogeneous group of diseases is examining targeted therapy, newer methods of radiotherapy, and predictors of response to therapy aiming to tailor management to an individual patient.

RTOG 9704 demonstrated a prognostic role for postoperative CA 19-9 in patients with resectable pancreatic carcinoma following surgery. Our study aimed to investigate whether CA 19-9 provided similar prognostic information in patients with locally advanced unresectable pancreatic cancer (LAPC) treated with chemoradiotherapy (CRT) and to determine whether such endpoints should therefore be reported in future randomized trials.Between December 1998 and October 2009, 253 patients with LAPC were treated with 5-fluourouracil-based concurrent CRT at our institution. Median radiation dose was 50.4 Gy. Only patients with a bilirubin of less than 2 mg/dL at the time the CA 19-9 was evaluated were included in the analysis to avoid the confounding effect of hyperbilirubinemia. Of the eligible patients, 54 had pre and post CRT CA 19-9 values available. The median age was 68 years and 52% were female. Categorized versions of the first post-CRT CA 19-9 were tested in 50 point increments beginning at50 to1,000 and percent change in pre to post-CRT CA 19-9 using cut points of 10% increments from0% (increased) to90%. Survival was measured from the date of first post CRT CA 19-9 level until death or last follow-up. Univariate and multivariate statistical methodologies were used to determine significant prognostic factors for overall survival.Median CA 19-9 prior to CRT was 363 U/mL and post CRT median was 85.5 U/mL. Following CRT, patients with a decrease of90% from their baseline CA 19-9 level had a significantly improved median survival than those that did not (16.2 vs. 7.5 months, P=0.01). The median survival of patients with a CA 19-9 level lower than the median post CRT value was 10.3 months, compared with 7.1 months for those with a CA 19-9 level greater than the median (P=0.03). Post CRT CA 19-9 less than 50 U/mL and histologic grade I-II also showed prognostic significance (both P=0.03). In multivariate analysis, post CRT CA 19-9 less than the median level of 85.5 U/mL was an independent prognostic factor for overall survival (HR 0.34; 95% CI, 0.13-0.85, P=0.02).Our results indicate that post treatment CA 19-9 is predictive for overall survival in patient with LAPC following CRT. We recommend that pre and post treatment CA 19-9 levels be obtained in patients receiving CRT and that these values be considered for prognostic nomograms and future clinical trials.

The NCCN Clinical Practice Guidelines in Oncology for Colon Cancer begin with the clinical presentation of the patient to the primary care physician or gastroenterologist and address diagnosis, pathologic staging, surgical management, perioperative treatment, patient surveillance, management of recurrent and metastatic disease, and survivorship. The NCCN Colon Cancer Panel meets annually to review comments from reviewers within their institutions and to reevaluate and update their recommendations. In addition, the panel has interim conferences as new data necessitate. These NCCN Guidelines Insights summarize the NCCN Colon Cancer Panel's discussions regarding the treatment of localized disease for the 2013 update of the guidelines.

To determine the effect of prostate cancer therapy (surgery or external beam irradiation, or both or none) on the actuarial incidence of subsequent bladder cancer.The Surveillance, Epidemiology, and End Results registry from 1973 to 2005 was analyzed. Treatment was stratified as radiotherapy, surgery, both surgery and adjuvant radiation, and neither modality. Brachytherapy was excluded.In all, 555,337 prostate carcinoma patients were identified; 124,141 patients were irradiated; 235,341 patients were treated surgically; 32,744 patients had both surgery and radiation; and 163,111 patients received neither modality. Bladder cancers were diagnosed in: 1,836 (1.48%) men who were irradiated (mean age, 69.4 years), 2,753 (1.09%) men who were treated surgically (mean age, 66.9 years); 683 (2.09%) men who received both modalities (mean age, 67.4 years), and 1,603 (0.98%) men who were treated with neither modality (mean age, 71.8 years). In each treatment cohort, Kaplan-Meier analyses showed that increasing age (by decade) was a significant predictor of developing bladder cancer (p0.0001). Incidence of bladder cancer was significantly different for either radiation or surgery alone versus no treatment, radiation versus surgery alone, and both surgery and radiation versus either modality alone (p0.0001). On multivariate analysis, age and irradiation were highly significant predictors of being diagnosed with bladder cancer.Following prostate cancer, increasing age and irradiation were highly significant predictors of being diagnosed with bladder cancer. While use of radiation increased the risk of bladder cancer compared to surgery alone or no treatment, the overall incidence of subsequent bladder cancer remained low. Routine bladder cancer surveillance is not warranted.

Purpose To identify factors predictive of renal atrophy after chemoradiotherapy of gastrointestinal malignancies. Methods and Materials Patients who received chemotherapy and abdominal radiotherapy (RT) between 2002 and 2008 were identified for this study evaluating change in kidney size and function after RT. Imaging and biochemical data were obtained before and after RT in 6-month intervals. Kidney size was defined by craniocaudal measurement on CT images. The primarily irradiated kidney (PK) was defined as the kidney that received the greater mean kidney dose. Receiver operating characteristic (ROC) curves were generated to predict risk for renal atrophy. Results Of 130 patients, median age was 64 years, and 51.5% were male. Most primary disease sites were pancreas and periampullary tumors (77.7%). Median follow-up was 9.4 months. Creatinine clearance declined 20.89%, and size of the PK decreased 4.67% 1 year after completion of chemoradiation. Compensatory hypertrophy of the non-PK was not seen. Percentage volumes of the PK receiving ≥10 Gy (V 10 ), 15 Gy (V 15 ), and 20 Gy (V 20 ) were significantly associated with renal atrophy 1 year after RT ( p = 0.0030, 0.0029, and 0.0028, respectively). Areas under the ROC curves for V 10 , V 15 , and V 20 to predict >5% decrease in PK size were 0.760, 0.760, and 0.762, respectively. Conclusions Significant detriments in PK size and renal function were seen after abdominal RT. The V 10 , V 15 , and V 20 were predictive of risk for PK atrophy 1 year after RT. Analyses suggest the association of lower-dose renal irradiation with subsequent development of renal atrophy.

To analyze clinical and dosimetric factors associated with change in renal function in patients with gastrointestinal malignancies after chemoradiation to the abdomen.A retrospective review of 164 patients with gastrointestinal malignancies treated between 2002 and 2007 was conducted to evaluate change in renal function after concurrent chemotherapy and three-dimensional conformal abdominal radiotherapy (RT). Laboratory and biochemical endpoints were determined before RT and after RT at 6-month intervals. Factors assessed included smoking, diabetes, hypertension, blood urea nitrogen, creatinine, creatinine clearance (CrCl), chemotherapy, and dose-volume parameters. Renal toxicity was assessed by decrease in CrCl and scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring schema.Of 164 patients, 63 had clinical and dosimetric data available. Median follow-up was 17.5 months. Creatinine clearance declined from 98.46 mL/min before RT to 74.20 mL/min one year after chemoradiation (p0.0001). Mean decrease in CrCl was 21.37%. Pre-RT CrCl, percentage of bilateral renal volume receiving at least 10 Gy (V(10)), and mean kidney dose were significantly associated with development of Gradeor =2 renal complications at 1 year after chemoradiation (p = 0.0025, 0.0170, and 0.0095, respectively).We observed correlation between pre-RT CrCl, V(10), and mean kidney dose and decline in CrCl 1 year after chemoradiation. These observations can assist in treatment planning and renal dose constraints in patients receiving chemotherapy and abdominal RT and may help identify patients at increased risk for renal complications.

e14659 Background: To retrospectively evaluate the outcome of borderline resectable (BR) and locally advanced unresectable (LA) pancreatic cancer patients treated with concurrent chemoradiotherapy (CRT) with gemcitabine (G) or capecitabine (C). Methods: Retrospective chart review of patients treated between August 2005 and September 2011 generated 30 BR and 40 LA pts. Cases were analyzed for patient and treatment characteristics including age, gender, weight loss, ECOG PS, albumin, stage, grade, location, pathology, laboratory values, chemotherapy (CT) regimens, radiotherapy dose and technique, and toxicity using CTCAE v.4.0. Endpoints evaluated were surgical resection rate, progression free survival (PFS), and median overall survival (mOS). Results: Patient characteristics were comparable between CRT/G and CRT/C in both BR and LA patients. Gemcitabine iv 300mg/m2 weekly or capecitabine po 825mg/m2 BID were used during CRT. Among BR patients who received CRT (n=21), 17 (56.6%) received CRT/G, 4 (13.3%) CRT/C, and others received CT alone. For BR, surgical resection was performed in 52.9% of CRT/G patients. The PFS were 17.4 months (m) and 4.8m (p=0.009), and mOS were 21.9m and 5.7m (p=0.004) for CRT/G and CRT/C respectively. For LA patients who received CRT (n=25), 18% of CRT/G underwent surgical resection and none of CRT/C did. The PFS 8.4m and 10.4m (p=0.63) and mOS were 14.9m and 11.5m (p=0.11) for CRT/G and CRT/C respectively. Comparing CRT and CT groups, mOS were not significantly different for LA patients, and longer for BR patients (14.4m vs. 5.5m) although this is likely due to confounding factors such as physician preference and patient selection. No significant differences were noted for grade 3/4 toxicities between both CRT groups. Conclusions: In this series, CRT/G in both BR and LA setting were associated with a high surgical resection rate with acceptable toxicity and potentially improved survival for patients not felt to be surgical candidates at presentation. These data warrant validation in larger prospective randomized studies.

e19041 Background: Treatment of locally advanced unresectable (LAU) or metastaticCSCC (mCSCC) is sub-optimal with a paucity of robust data on systemic therapy. Platinum or fluorouracil-based chemotherapy is commonly used. This retrospective study aimed to evaluate the efficacy and outcomes of patients (pts) with LAU or mCSCC treated with systemic therapy. Methods: Records ofpts with CSCC treated with systemic therapy from Jan ‘01 – Jan ‘11 were reviewed. Response was assessed using WHO criteria. Descriptive results were assessed using Wilcoxon Rank Sum test for ordinal responses and Pearson Chi-square test for categorical responses. Survival was calculated by the Kaplan-Meier method. Results: Of 28 pts identified, 25 pts (M:F – 18:7), median age 66 yrs (39, 85) had required data for final analysis. 11 pts (44%) had facial primary tumors (including 7 of the external ear). 19 pts (76%) had LAU and 6 pts had mCSCC. 17 pts (68%) received multi-agent 1st-line chemotherapy (CT). 72%, 76% and 48% pts received platinum, taxane or cetuximab respectively as part of their regimens. 14 pts got 2nd line therapy and 4 pts received concurrent radiation therapy. Partial response (PR) was 44% and 24% pts had stable disease (SD) for a disease control rate of 68%. With a median follow-up of 42.8m, the median progression-free (PFS) and overall survival (OS) were 5.5m (2.3, 13.2) and 10.9m (5.3, 21.3) respectively; 3-yr OS was 22%. Pts with WHO response had improved PFS (20.8m; 4.4, NR; p

e14712 Background: Esophageal and gastroesophageal junction (GEJ) adenocarcinoma is increasingly treated with trimodality therapy. We present our experience using carboplatin/paclitaxel and radiotherapy followed by surgery. Methods: Consecutive patients with distal esophageal/GEJ adenocarcinoma (≥T2 or N+) treated from July 2010 to October 2011 were identified. All patients received neoadjuvant carboplatin/paclitaxel with concurrent radiotherapy (CRT) to 50.4 Gy using an IMRT technique and then Ivor Lewis esophagogastrectomy. PET/CT was performed prior to and after CRT. Patient/treatment characteristics and tumor response were analyzed. Results: Over this timeframe,17 patients completed trimodality therapy using this regimen. All were male with a median age of 59 years (45-72). All tumors were grade 2-3 adenocarcinoma with mean tumor length of 4.4 cm (1-9). A median of 6 cycles (5-9) neoadjuvant carboplatin/paclitaxel were administered, 3 patients received additional adjuvant therapy. Average time from diagnosis to CRT completion was 78 days (44-141) and from CRT end to surgery was 62 days (35-92). Neoadjuvant CRT was well tolerated with mean weight loss of 3.5 kg. All pts had R0 resections. No anastomotic leaks or perioperative mortality occurred. Mean hospital stay was 13.6 days (8-28). Pathologic complete response (pCR) was seen in 41% of patients, microscopic residual disease (isolated tumor cells or

Purpose/Objective(s): There is little published information on the results of neoadjuvant chemoradiotherapy (CRT) followed by surgery in older patients due to the presumed increased risk for morbidity and mortality. We report our single institutional experience of trimodality therapy in patients with esophageal carcinoma 65 years of age or older. Materials/Methods: Patients treated with preoperative CRT followed by esophagectomy from 2002-2010 were identified for this IRB approved retrospective study. Patient and treatment characteristics, tolerance, response, and survival were analyzed in patients ≥ 65 years of age versus patients 65 years of age (26.1%), 19 patients were >70 years. Median follow up was 27.5 months (range 5.093.8), and 93.3% of patients were treated to a median dose of 50.4 Gy with concurrent non-cisplatin/5-fluorouracil based concurrent chemotherapy. Between groups, there were no differences in gender, performance status, diabetes, cardiac history, pulmonary disease, smoking status, histology, radiation dose, days to completion of CRT, or days from completion of CRT to surgery. Overall peri-operative mortality was low, with no 30 day mortality and 3.5% 60 day mortality; both mortalities occurred in patients >70 years. The median length of post-operative hospital stay for patients >65 years was 15.5 days versus 11.0 days for patients 65 years compared to patients 65 years of age, median survival was 35.2 months and 3 and 5 year overall survival rates were 45.9% and 37.1% respectively. Conclusions: These data suggest that older patients can be appropriately selected for neoadjuvant chemoradiotherapy followed by surgery when a comprehensive multidisciplinary approach is utilized. Age alone should not preclude consideration for trimodality therapy in patients with esophageal carcinoma.

Mean size of the primary radiated kidney was reduced from 104.1 mm (range 100–120, SD 13.1) before treatment to 93.8 mm (range 85–120, SD 13.3) at 1 year after radiotherapy (p < 0.0001). Mean size of the non-primary radiated kidney was reduced from 109.4 mm (range 80–125, SD 8.3) before treatment to 105.0 mm (range 70–120, SD 10.2) at 1 year after radiotherapy (p = 0.06), table 1. Mean creatinine was increased from 0.84 mg/dl (range 0.5-1.3) before treatment to 0.94 mg/dl (range 0.6-1.4) after radiotherapy (p = 0.08).

The NCCN Clinical Practice Guidelines in Oncology for Colon Cancer begin with the clinical presentation of the patient to the primary care physician or gastroenterologist and address diagnosis, pathologic staging, surgical management, perioperative treatment, patient surveillance, management of recurrent and metastatic disease, and survivorship. The NCCN Colon Cancer Panel meets annually to review comments from reviewers within their institutions and to reevaluate and update their recommendations. In addition, the panel has interim conferences as new data necessitate. These NCCN Guidelines Insights summarize the NCCN Colon Cancer Panel's discussions regarding the treatment of localized disease for the 2013 update of the guidelines.