Metastatic colon cancer, version 3.2013: featured updates to the NCCN Guidelines.

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.

Localized colon cancer, version 3.2013: featured updates to the NCCN Guidelines.

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.

Rectal cancer.

These NCCN Clinical Practice Guidelines in Oncology provide recommendations for the management of rectal cancer, beginning with the clinical presentation of the patient to the primary care physician or gastroenterologist through diagnosis, pathologic staging, neoadjuvant treatment, surgical management, adjuvant treatment, surveillance, management of recurrent and metastatic disease, and survivorship. This discussion focuses on localized disease. The NCCN Rectal Cancer Panel believes that a multidisciplinary approach, including representation from gastroenterology, medical oncology, surgical oncology, radiation oncology, and radiology, is necessary for treating patients with rectal cancer.

Anal Carcinoma, Version 2.2012: featured updates to the NCCN guidelines.

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.

Change in CA 19-9 levels after chemoradiotherapy predicts survival in patients with locally advanced unresectable pancreatic cancer.

PURPOSE: 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. METHODS AND MATERIALS: 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 at <50 to >1,000 and percent change in pre to post-CRT CA 19-9 using cut points of 10% increments from <0% (increased) to >90%. 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. RESULTS: 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 of >90% 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). CONCLUSIONS: 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.

Treatment of locally advanced unresectable pancreatic cancer: a 10-year experience.

PURPOSE: We retrospectively analyzed the results of patients with locally advanced unresectable pancreatic cancer (LAPC) treated with either chemoradiation (CRT) or chemotherapy alone over the past decade. METHODS AND MATERIALS: Between December 1998 and October 2009, 116 patients with LAPC were treated at our institution. Eighty-four patients received concurrent chemoradiation [RT (+) group], primarily 5-flourouracil based (70%). Thirty-two patients received chemotherapy alone [RT (-) group], the majority gemcitabine based (78%). Progression-free survival (PFS) and overall survival (OS) were calculated from date of diagnosis to date of first recurrence and to date of death or last follow-up, respectively. Univariate statistical analysis was used to determine significant prognostic factors for overall survival. RESULTS: Median patient age was 67 years. Sixty patients were female (52%). Median follow-up was 11 months (range, 1.6-59.4 months). The RT (+) group received a median radiation dose of 50.4 Gy, was more likely to present with ECOG 0-1 performance status, and experienced less grade 3-4 toxicity. PFS was 10.9 versus 9.1 months (P=0.748) and median survival was 12.5 versus 9.1 months (P=0.998) for the RT (+) and RT (-) groups respectively (P=0.748). On univariate analysis, patients who experienced grade 3-4 toxicity had worse overall survival than those who did not (P=0.02). CONCLUSIONS: Optimal management for LAPC continues to evolve. Patients who developed treatment-related grade 3-4 toxicity have a poorer prognosis. Survival rates were not statistically significant between chemotherapy and chemoradiotherapy groups.

Increasing age and treatment modality are predictors for subsequent diagnosis of bladder cancer following prostate cancer diagnosis.

PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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 (p < 0.0001). 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 (p < 0.0001). On multivariate analysis, age and irradiation were highly significant predictors of being diagnosed with bladder cancer. CONCLUSIONS: 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.

Renal atrophy secondary to chemoradiotherapy of abdominal malignancies.

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.

Analysis of clinical and dosimetric factors associated with change in renal function in patients with gastrointestinal malignancies after chemoradiation to the abdomen.

PURPOSE: To analyze clinical and dosimetric factors associated with change in renal function in patients with gastrointestinal malignancies after chemoradiation to the abdomen. METHODS AND MATERIALS: 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. RESULTS: 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 (p < 0.0001). 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 Grade > or =2 renal complications at 1 year after chemoradiation (p = 0.0025, 0.0170, and 0.0095, respectively). CONCLUSIONS: 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.

Association of Technetium(99m) MAG-3 renal scintigraphy with change in creatinine clearance following chemoradiation to the abdomen in patients with gastrointestinal malignancies.

BACKGROUND: Information on differential renal function following abdominal chemoradiation is limited. This study evaluated the association between renal function as measured by biochemical endpoints and scintigraphy and dose volume parameters in patients with gastrointestinal malignancies. MATERIALS AND METHODS: Patients who received abdominal chemoradiation between 2002 and 2009 were identified for this study. Technetium(99m) MAG-3 scintigraphy and laboratory data were obtained prior to and after chemoradiation in 6 month intervals. Factors assessed included age, gender, hypertension, diabetes, and dose volume parameters. Renal function was assessed by biochemical endpoints and renal scintigraphy. RESULTS: Significant reductions in relative renal function of the primarily irradiated kidney and creatinine clearance were seen. Split renal function decreased from 49.75% pre-radiation to 47.74% and 41.28% at 6-12 months and >12 months post-radiation (P=0.0184). Creatinine clearance declined from 90.67ml/min pre-radiation to 82.23ml/min and 74.54ml/min at 6-12 months and >12 months post-radiation (P<0.0001). Univariate analysis of patients who had at least one post-radiation renogram showed the percent volumes of the primarily irradiated kidney receiving ≥ 25 Gy (V(25)) and 40 Gy (V(40)) were significantly associated with ≥5% decrease in relative renal function (P=0.0387 and P=0.0438 respectively). CONCLUSION: Decline in split renal function using Technetium(99m) MAG-3 scintigraphy correlates with decrease in creatinine clearance and radiation dose-volume parameters following abdominal chemoradiation. Change in split perfusion can be detected as early as 6 months post-radiation. Scintigraphy may provide early determination and quantification of subclinical renal injury prior to clinical evidence of nephropathy.